Long-Term Medication Profiles in Parkinson's Disease under Subthalamic Deep Brain Stimulation: A Controlled Study.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking. OBJECTIVE: To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients. METHODS: We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities. RESULTS: In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists. CONCLUSION: In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.

Emotion Recognition in Multiple System Atrophy: An Exploratory Eye-Tracking Study.

OBJECTIVE: Emotional processing is a core feature of social interactions and has been well studied in patients with idiopathic Parkinson's disease (PD), albeit with contradictory. RESULTS: . However, these studies excluded patients with atypical parkinsonism, such as multiple system atrophy (MSA). The objective of this exploratory study was to provide better insights into emotion processing in patients with MSA using eye tracking data. METHODS: We included 21 MSA patients, 15 PD patients and 19 matched controls in this study. Participants performed a dynamic and a static emotion recognition task, and gaze fixations were analyzed in different areas of interest. Participants underwent neuropsychological testing and assessment of depression and alexithymia. RESULTS: MSA patients were less accurate in recognizing anger than controls (p = 0.02) and had overall fewer fixations than controls (p = 0.001). In the static task, MSA patients had fewer fixations (p < 0.001) and a longer time to first fixation (p = 0.026) on the eye region. Furthermore, MSA patients had a longer fixation duration overall than PD patients (p = 0.004) and longer fixations on the nose than controls (p = 0.005). Alexithymia scores were higher in MSA patients compared to controls (p = 0.038). CONCLUSION: This study demonstrated impaired recognition of anger in MSA patients compared to HCs. Fewer and later fixations on the eyes along with a center bias suggest avoidance of eye contact, which may be a characteristic gaze behavior in MSA patients.

Development and Validation of a Prognostic Model to Predict Overall Survival in Multiple System Atrophy.

Background: Multiple system atrophy (MSA) is a devastating disease characterized by a variable combination of motor and autonomic symptoms. Previous studies identified numerous clinical factors to be associated with shorter survival. Objective: To enable personalized patient counseling, we aimed at developing a risk model of survival based on baseline clinical symptoms. Methods: MSA patients referred to the Movement Disorders Unit in Innsbruck, Austria, between 1999 and 2016 were retrospectively analyzed. Kaplan-Meier curves and multivariate Cox regression analysis with least absolute shrinkage and selection operator penalty for variable selection were performed to identify prognostic factors. A nomogram was developed to estimate the 7 years overall survival probability. The performance of the predictive model was validated and calibrated internally using bootstrap resampling and externally using data from the prospective European MSA Study Group Natural History Study. Results: A total of 210 MSA patients were included in this analysis, of which 124 patients died. The median survival was 7 years. The following clinical variables were found to significantly affect overall survival and were included in the nomogram: age at symptom onset, falls within 3 years of onset, early autonomic failure including orthostatic hypotension and urogenital failure, and lacking levodopa response. The time-dependent area under curve for internal and external validation was >0.7 within the first 7 years of the disease course. The model was well calibrated showing good overlap between predicted and actual survival probability at 7 years. Conclusion: The nomogram is a simple tool to predict survival on an individual basis and may help to improve counseling and treatment of MSA patients.

Cardiac sympathetic innervation in Parkinson's disease versus multiple system atrophy.

PURPOSE: The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy. METHODS: A prospective study including 19 Parkinson's disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests. RESULTS: Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson's disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson's disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson's disease patients (p < 0.001). CONCLUSIONS: The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson's disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson's disease patients.

Has Deep Brain Stimulation Changed the Very Long-Term Outcome of Parkinson's Disease? A Controlled Longitudinal Study.

BACKGROUND: The long-term impact of deep brain stimulation (DBS) on Parkinson's disease (PD) is difficult to assess and has not yet been rigorously evaluated in comparison to its natural history. OBJECTIVE: Comparison of key disability milestones (recurrent falls, psychosis, dementia, and institutionalization) and death in patients with PD with versus without DBS. METHODS: We collected retrospective information from clinical notes of patients with PD at our center that were implanted with subthalamic DBS >8 years ago (1999-2010) and a control group of PD patients without DBS similar in age at onset, age at baseline, sex distribution, and number of comorbidities at baseline (extracted from a registry study performed in 2004). Cox regression models were used to calculate hazard ratios, adjusted for potential baseline confounding variables (age, sex, disease duration, disease severity, and number of comorbidities). RESULTS: A total of 74 DBS-treated and 61 control patients with PD were included. For a median observational period of 14 years, patients treated with DBS were at lower risk of experiencing recurrent falls (hazard ratio = 0.57; 95% confidence interval, 0.37-0.90; P = 0.015) and psychosis (hazard ratio = 0.26; 95% confidence interval, 0.12-0.59; P = 0.001) compared with control patients. There was no significant difference in risk for dementia, institutionalization, or death. Disease progression as assessed by Hoehn and Yahr scores was not slower in DBS-treated patients. CONCLUSIONS: Treatment with chronic subthalamic DBS was associated with lower risk for recurrent falls and psychotic symptoms, effects that may be mediated through improved motor symptom control and reduction in dopaminergic therapies, respectively. There was no evidence for DBS effects on underlying disease progression.

Cognition in multiple system atrophy: a single-center cohort study.

OBJECTIVE: Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between-group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition. METHODS: This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work-up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD-plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS-D). RESULTS: The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P < 0.05) in a screening of executive functions (FAB) and in phonemic verbal fluency. Depression and anxiety scores were elevated in 28% and 22% of MSA patients, respectively. Cognitive profile, depression, and anxiety levels were comparable between patients with and without OH. INTERPRETATION: Cognitive deficits are relatively frequent in MSA and primarily affect executive functions and verbal memory. Future comparative studies including Parkinson dementia, Lewy body disease, and MSA cases with and without OH are required to elucidate disease-specific cognitive profiles in these synucleinopathies and to examine the influence of cardiovascular autonomic dysfunction on cognitive function in MSA.

Prevalence and Associated Factors of Sarcopenia and Frailty in Parkinson's Disease: A Cross-Sectional Study.

BACKGROUND: Sarcopenia and frailty are found in up to one-third of the general elderly population. Both are associated with major adverse health outcomes such as nursing home placement, disability, decreased quality of life, and death. Data on the frequency of both syndromes in Parkinson's disease (PD), however, are very limited. OBJECTIVE: We aimed to screen for sarcopenia and frailty in PD patients and to assess potential associations of both geriatric syndromes with demographic and clinical parameters as well as quality of life. METHODS: In this observational, cross-sectional study, we included 104 PD patients from a tertiary center and 330 non-PD controls from a population-based cohort aged > 65 years. All groups were screened for sarcopenia using the SARC-F score and for frailty using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD patients from a population-based cohort aged > 65 years. Moreover, PD patients from the tertiary center were evaluated for motor and non-motor symptoms, quality of life, and dependency. RESULTS: The prevalence of sarcopenia was 55.8% (95% CI: 46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p < 0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2% (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3% (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based PD sample. Both sarcopenia and frailty were significantly associated with longer disease duration, higher motor impairment, higher Hoehn and Yahr stages, decreased quality of life, higher frequency of falls, a higher non-motor symptom burden, institutionalization, and higher care levels in PD patients from a tertiary center compared to not affected PD patients (all p < 0.05). CONCLUSIONS: Both frailty and sarcopenia are more common in PD patients than in the general community and are associated with a more adverse course of the disease. Future studies should look into underlying risk factors for the occurrence of sarcopenia and frailty in PD patients and into adequate management to prevent and mitigate them.

Cerebral Phosphorus Magnetic Resonance Spectroscopy in a Patient with Giant Cell Arteritis and Endovascular Therapy.

With phosphorus magnetic resonance spectroscopy (31P MRS) energy metabolites can be visualised. In this case study, we report on a patient with stenosis and wall contrast enhancement in the left internal carotid and the right vertebral artery, due to giant cell arteritis. 31P MRS revealed a decreased inorganic phosphate-to-phosphocreatine ratio (Pi/PCr) in regions with a prolonged mean transit time (MTT). After systemic therapy and angioplasty of the right vertebral artery, the stenosis and the symptoms improved and the area of prolonged MTT became smaller. However, a new decrease in Pi/PCr in areas that developed moderately prolonged MTT was observed.

The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism.

INTRODUCTION: The hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism. METHODS: Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up. RESULTS: 481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement. CONCLUSION: Midbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages.

Consistency of "Probable RBD" Diagnosis with the RBD Screening Questionnaire: A Follow-up Study.

INTRODUCTION: The aim of this study was to evaluate the consistency of "probable RBD" diagnosis with the RBD screening questionnaire (RBDSQ) assessed 2 years apart in a population-based study. METHODS: Probable RBD was assessed by RBDSQ in 2008 and in 2010 in the Bruneck Study Cohort, with participants aged ≥60 years. RESULTS: A total of 437 participants completed the RBDSQ in 2008 and 2010. There were 29 (6.6%) and 23 (5.3%) participants with probable RBD in 2008 and in 2010, respectively. Only eight (1.8%) screened positive on both occasions. RBDSQ values 2 years apart showed low correlation with each other (Spearman rank coefficient r = 0.348, P < 0.001) and low agreement (intraclass correlation coefficient 0.388, P < 0.001). CONCLUSIONS: We found low agreement between the two assessments. Possible explanations are the fluctuation of untreated RBD expression and the poor utility of the RBDSQ to detect RBD in the general population. Until further PSG validation of the RBDSQ in population-based studies, investigators must be aware of the inherent uncertainty of questionnaire-based RBD diagnosis.

Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community.

BACKGROUND: Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinson's disease (PD), but to date their predictive value has not yet been tested in population-based cohorts. METHODS: We retrospectively applied these criteria to the longitudinal Bruneck Study cohort aged 55-94 years using recorded data on all included risk and prodromal markers that are quick and easily assessable. RESULTS: After excluding participants with idiopathic PD or secondary parkinsonism, prevalence of probable prodromal PD in the remaining 539 participants was 2.2% (95% confidence interval, 1.2%-3.9%). Of 488 participants followed up over 5 years, 11 developed incident PD. Sensitivity of "probable prodromal PD" status for incident PD was 54.6% (95% confidence interval, 28.0%-78.8%), specificity was 99.2% (97.8%-99.8%), positive predictive value was 60.0% (31.2%-83.3%), and negative predictive value was 99.0% (97.5%-99.6%). CONCLUSIONS: Our findings suggest that the new research criteria for prodromal PD are a promising tool to identify cases of incident PD over 5 years, arguing for their usefulness in defining target populations for disease-prevention trials. © 2016 International Parkinson and Movement Disorder Society.

Nonmotor symptoms in subjects without evidence of dopaminergic deficits.

BACKGROUND: A subgroup of patients initially diagnosed with Parkinson's disease (PD) turn out to have normal dopamine transporter single-photon emission computed tomography imaging and have been labeled as subjects without evidence of dopaminergic deficit (SWEDDs). In this study, we sought to further characterize these patients and have analyzed the frequency of nonmotor symptoms (NMS) in SWEDDs, PD patients, and healthy controls. METHODS: We analyzed the baseline clinical data of 412 PD patients, 184 controls, and 62 SWEDDs included in the Parkinson's Progression Marker Initiative study on a variety of different NMS questionnaires. RESULTS: Both PD patients and SWEDDs had greater frequency of NMS than healthy controls. Furthermore, some NMS, such as orthostatic hypotension as well as cardiovascular and thermoregulatory dysfunction were even more commonly reported in SWEDDs than in PD patients, whereas hyposmia was more common in PD, compared to SWEDDs. CONCLUSION: NMS are more frequent in SWEDDs than in controls, and autonomic dysfunction and orthostatic hypotension were even more common than in PD patients. These findings support the notion that SWEDDS represent a group of patients with still poorly understood pathophysiology. © 2015 International Parkinson and Movement Disorder Society.

Left hemispheric predominance of nigrostriatal dysfunction in Parkinson's disease.

The aim of this study was to investigate the distribution and the degree of asymmetric putaminal dopamine transporter availability in right-handed patients with Parkinson's disease and its association with the severity of lateralized motor signs. Asymmetry of motor symptoms was defined by the difference between right- and left-sided scores for lateralized items assessed by the Unified Parkinson's Disease Rating Scale Motor Score in a series of 68 patients with Parkinson's disease (disease duration 2.1 ± 1.5 years; Unified Parkinson's Disease Rating Scale Motor Score 22.7 ± 9). Putaminal dopamine transporter availability was measured with the radioligand [(123)I]ß-carboxymethyoxy-3 -ß-(4-iodophenyl) tropane ([(123)I]ß-CIT) and single photon emission computed tomography. We found that in the right-handed Parkinson's disease cohort, the number of patients who had lower dopamine transporter uptake in the left posterior putamen was significantly greater compared with those with lower uptake in the right posterior putamen (Parkinson's disease-left group, n = 49; Parkinson's disease-right group, n = 19; P < 0.001). In addition, one-way analysis of variance revealed significant reductions of mean total putaminal [(123)I]ß-CIT binding of the Parkinson's disease-right patients compared with Parkinson's disease-left patients (P < 0.05).The preponderance of reduced left putaminal dopamine transporter availability strengthens clinical observations of a greater proportion of right-handed patients with Parkinson's disease with predominantly right-sided motor signs and argues against a randomly distributed asymmetric vulnerability of substantia nigra dopaminergic neurons. The coexistence of a subgroup of right-handed patients with Parkinson's disease with more severe and predominant ipsilateral putaminal dopamine transporter decline suggests that asymmetry of dopaminergic denervation and motor dysfunction in Parkinson's disease cannot be fully explained by hemispheric dominance alone, but that other factors must be involved.

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

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

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

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

Seminar on choreas.

Chorea is one of the major types of involuntary movement disorders originating from dysfunctional neuronal networks interconnecting the basal ganglia and frontal cortical motor areas. The syndrome is characterised by a continuous flow of random, brief, involuntary muscle contractions and can result from a wide variety of causes. Diagnostic work-up can be straightforward in patients with a positive family history of Huntington's disease or acute-onset hemichorea in patients with lacunar stroke, but it can be a challenging and complex task in rare autoimmune or genetic choreas. Principles of management focus on establishing an aetiological classification and, if possible, removal of the cause. Preventive strategies may be possible in Huntington's disease where genetic counselling plays a major part. In this review we summarise the current understanding of the neuroanatomy and pathophysiology of chorea, its major aetiological classes, and principles of diagnostic work-up and management.

Parkinson's disease and arithmetics: the role of executive functions.

Brain imaging studies as well as neuropsychological case studies suggest an important role for basal ganglia in arithmetic processing. Aim of this study was to assess possible numerical deficits in PD and functional relations between numerical and other cognitive deficits. Fifteen non-demented patients with early PD (stable responders treated by l-dopa) were compared to 28 healthy age and education matched controls. Both groups underwent a neuropsychological assessment focussing on numerical abilities (quantity processing, arithmetic fact retrieval, complex mental and written calculation, transcoding, arithmetic set-shifting, calculation span), working memory and executive functions. Patients with PD showed deficits in complex mental calculation and calculation span tasks. Results of this study suggest that impairments in working memory as well as in executive functions, such as inhibition of interference, lead to secondary deficits in numerical processing. The study contributes to better understanding the specific cognitive deficits in early PD and the neurocognitive architecture of arithmetic processing.

Diffusion-weighted imaging in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder that results from an expanded trinucleotide (CAG) repeat on the huntingtin gene. Neurodegeneration in HD affects most prominently the basal ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of 29 patients with early HD and 27 healthy volunteers by means of the trace of the diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D) values were increased in patients with HD compared with controls. Increased diffusivity in the putamen and caudate nucleus correlated with global functional impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally.

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

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

Progression of putaminal degeneration in multiple system atrophy: a serial diffusion MR study.

By using diffusion-weighted imaging (DWI), we have recently shown abnormal diffusivity in the putamen of patients with the Parkinson variant of multiple system atrophy (MSA-P) which also correlated with disease severity, indicating the capability of putaminal diffusivity to serve as a marker for disease progression. We therefore performed a serial DWI study in 10 patients with MSA-P compared to 10 patients with Parkinson's disease (PD) to evaluate the dynamic evolution of diffusion properties in the basal ganglia including putamen, caudate nucleus and globus pallidum by means of the trace of the diffusion tensor (Trace(D)). For comparison, we have also analyzed the frequency and semiquantitative grading of MSA-P-related structural changes on conventional MRI including putaminal atrophy, lateral hyperintense margination of the putamen and putaminal signal hypointensity relative to the globus pallidum on T2 MR images. None of the Trace(D) values in the basal ganglia regions in the PD group changed significantly at follow-up compared to baseline. In MSA-P, a significant increase of the Trace(D) was found in the putamen, which correlated with motor progression as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). No significant change of any of the abnormal putaminal findings on routine MRI was obtained. We suggest that abnormal diffusivity in the putamen is sensitive to change over time in MSA-P and correlates with motor progression indicating that DWI may serve to monitor disease progression in MSA-P in an objective and quantitative manner.