The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

Segmental Alterations of the Corpus Callosum in Progressive Supranuclear Palsy: A Multiparametric Magnetic Resonance Imaging Study.

Background: The regional distribution of the widespread cerebral morphological alterations in progressive supranuclear palsy (PSP) is considered to include segmental parts of the corpus callosum (CC). Objective: The study was designed to investigate the regional white matter (WM) of the CC by T1 weighted magnetic resonance imaging (T1w MRI) data combined with diffusion tensor imaging (DTI) data in PSP patients, differentiated in the variants Richardson syndrome and PSP-parkinsonism, and to compare them with Parkinson's Disease (PD) patients and healthy controls, in order to identify macro- and micro-structural alterations in vivo. Methods: MRI-based WM mapping was used to perform an operator-independent segmentation for the different CC segments in 66 PSP patients vs. 66 PD patients vs. 44 matched healthy controls. The segmentation was followed by both planimetric and texture analysis of the separated CC areas for the comparison of the three groups. Results were complemented by a DTI-based tract-of-interest analysis of the associated callosal tracts. Results: Significant alterations of the parameters entropy and homogeneity compared to controls were observed for PSP as well as for PD for the CC areas I, II, and III. The inhomogeneity in area II in the PSP cohort was the highest and differed significantly from PD. A combined score was defined as a potential marker for the different types of neurodegenerative parkinsonism; receiver operating characteristics (ROC) curves were calculated with areas under the curve values of 0.86 for PSP vs. controls, 0.72 for PD vs. controls, and 0.69 for PSP vs. PD, respectively. Conclusion: The multiparametric MRI texture and DTI analysis demonstrated extensive alterations of the frontal CC in neurodegenerative parkinsonism, whereas regional CC atrophy cannot be regarded as a constant neuroimaging feature of PSP. Specifically, the comparison PSP vs. PD revealed significant alterations in callosal area II. The combination of the texture and the DTI parameters might contribute as a neuroimaging marker for the assessment of the CC in PSP, including the differentiation vs. PD.

MRI as a first-line imaging modality in acute ischemic stroke: a sustainable concept.

BACKGROUND: Computed tomography (CT) scans are the first-line imaging technique in acute stroke patients based on the argument of rapid feasibility. Using magnetic resonance imaging (MRI) as the first-line imaging technique is the exception to the rule, although it provides much more diagnostic information and avoids exposure to radiation. We evaluated whether an MRI-based acute stroke concept is fast, suitable, and useful to improve recanalization rates and patient outcomes. METHODS: We performed a retrospective observational cohort study comparing patients treated at a comprehensive stroke center (Ulm/Germany) applying an MRI-based acute stroke concept with patients recorded in a large comprehensive stroke registry in Baden-Württemberg (Germany). We analyzed the quality indicators of acute stroke treatment, patient's outcome, and the rate of transient ischemic attack (TIA) at discharge. RESULTS: A total of 2182 patients from Ulm and 82,760 patients from the Baden-Württemberg (BW) stroke registry (including 29,575 patients of comprehensive stroke centers (BWc)) were included. Intravenous thrombolysis rate was higher in Ulm than in BW or the BWc stroke centers (Ulm 27.4% versus BW 20.9% versus BWc 26.1; p < 0.01), while a door-to-needle time <30 min could be achieved more frequently (Ulm 73.6% versus BW 44.1% versus BWc 47.1%; p < 0.01). Thrombectomy rate in patients with a proximal vascular occlusion was higher (Ulm 69.2% versus BW 50.7% versus BWc 59.3; p < 0.01). The number of TIA diagnoses was lower (Ulm 16.2% versus BW 24.6% versus BWc 19.9%; p < 0.01). More patients showed a shift to a favorable outcome (Ulm 21.1% versus BW 16.9% versus BWc 15.3; p < 0.01). Complication rates were similar. CONCLUSIONS: The MRI-based acute stroke concept is suitable, fast and seems to be beneficial. The time-dependent quality indicators were better both in comparison to all stroke units and to the comprehensive stroke units in the area. Based on the MRI concept, high rates of recanalization procedures and fewer TIA diagnoses could be observed. In addition, there was a clear trend towards an improved clinical outcome. A clinical trial comparing the effects of CT and MRI as the primary imaging technique in otherwise identical stroke unit settings is warranted.

The differential diagnostic value of a battery of oculomotor evaluation in Parkinson's Disease and Multiple System Atrophy.

INTRODUCTION: Clinical diagnosis of Parkinsonism is still challenging, and the diagnostic biomarkers of Multiple System Atrophy (MSA) are scarce. This study aimed to investigate the diagnostic value of the combined eye movement tests in patients with Parkinson's disease (PD) and those with MSA. METHODS: We enrolled 96 PD patients, 33 MSA patients (18 with MSA-P and 15 with MSA-C), and 40 healthy controls who had their horizontal ocular movements measured. The multiple-step pattern of memory-guided saccade (MGS), the hypometria/hypermetria of the reflexive saccade, the abnormal saccade in smooth pursuit movement (SPM), gaze-evoked nystagmus, and square-wave jerks in gaze-holding test were qualitatively analyzed. The reflexive saccadic parameters and gain of SPM were also quantitatively analyzed. RESULTS: The MGS test showed that patients with either diagnosis had a significantly higher incidence of multiple-step pattern compared with controls (68.6%, 65.2%, and versus. 2.5%, p < .05, in PD, MSA, versus. controls, respectively). The reflexive saccade test showed that MSA patients showing a prominent higher incidence of the abnormal saccade (63.6%, both hypometria and hypermetria) than that of PD patients and controls (33.3%, 7.5%, respectively, hypometria) (p < .05). The SPM test showed PD patients had mildly decreased gain among whom 28.1% presenting "saccade intrusions"; and that MSA patients had the significant decreased gain with 51.5% presenting "catch-up saccades"(p < .05). Only MSA patients showed gaze-evoked nystagmus (24.2%), square-wave jerks (6.1%) in gaze-holding test (p < .05). CONCLUSIONS: A panel of eye movements tests may help to differentiate PD from MSA. The combined presence of hypometria and hypermetria in saccadic eye movement, the impaired gain of smooth pursuit movement with "catch-up saccades," gaze-evoked nystagmus, square-wave jerks in gaze-holding test, and multiple-step pattern in MGS may provide clues to the diagnosis of MSA.

Diagnostic value of video-oculography in progressive supranuclear palsy: a controlled study in 100 patients.

BACKGROUND: The eponymous feature of progressive supranuclear palsy (PSP) is oculomotor impairment which is one of the relevant domains in the Movement Disorder Society diagnostic criteria. OBJECTIVE: We aimed to investigate the value of specific video-oculographic parameters for the use as diagnostic markers in PSP. METHODS: An analysis of video-oculography recordings of 100 PSP patients and 49 age-matched healthy control subjects was performed. Gain of smooth pursuit eye movement and latency, gain, peak eye velocity, asymmetry of downward and upward velocities of saccades as well as rate of saccadic intrusions were analyzed. RESULTS: Vertical saccade velocity and saccadic intrusions allowed for the classification of about 70% and 56% of the patients, respectively. By combining both parameters, almost 80% of the PSP patients were covered, while vertical velocity asymmetry was observed in approximately 34%. All parameters had a specificity of above 95%. The sensitivities were lower with around 50-60% for the velocity and saccadic intrusions and only 27% for vertical asymmetry. CONCLUSIONS: In accordance with oculomotor features in the current PSP diagnostic criteria, video-oculographic assessment of vertical saccade velocity and saccadic intrusions resulted in very high specificity. Asymmetry of vertical saccade velocities, in the opposite, did not prove to be useful for diagnostic purposes.

Eye movement alterations in presymptomatic C9orf72 expansion gene carriers.

OBJECTIVE: The clinical manifestation of amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration, whereas frontotemporal dementia (FTD) patients show alterations of behavior and cognition. Both share repeat expansions in C9orf72 as the most prevalent genetic cause. Before disease-defining symptoms onset, structural and functional changes at cortical level may emerge in C9orf72 carriers. Here, we characterized oculomotor parameters and their association to neuropsychological domains in apparently asymptomatic individuals with mutations in ALS/FTD genes. PATIENTS AND METHODS: Forty-eight carriers of ALS genes, without any clinical symptoms underwent video-oculographic examination, including 22 subjects with C9orf72 mutation, 17 with SOD1, and 9 with other ALS associated gene mutations (n = 3 KIF5A; n = 3 FUS/FUS + TBK1; n = 1 NEK1; n = 1 SETX; n = 1 TDP43). A total of 17 subjects underwent a follow-up measurement. Data were compared to 54 age- and gender-matched healthy controls. Additionally, mutation carriers performed a neuropsychological assessment. RESULTS: In comparison to controls, the presymptomatic subjects performed significantly worse in executive oculomotor tasks such as the ability to perform correct anti-saccades. A gene mutation subgroup analysis showed that dysfunctions in C9orf72 carriers were much more pronounced than in SOD1 carriers. The anti-saccade error rate of ALS mutation carriers was associated with cognitive deficits: this correlation was increased in subjects with C9orf72 mutation, whereas SOD1 carriers showed no associations. CONCLUSION: In C9orf72 carriers, executive eye movement dysfunctions, especially the increased anti-saccade error rate, were associated with cognitive impairment and unrelated to time. These oculomotor impairments are in support of developmental deficits in these mutations, especially in prefrontal areas.

The intrinsically restructured fovea is correlated with contrast sensitivity loss in Parkinson's disease.

Foveal structure that is specified by the thickness, depth and the overall shape of the fovea is a promising tool to qualify and quantify retinal pathology in Parkinson's disease. To determine the model variable that is best suited for discriminating Parkinson's disease eyes from those of healthy controls and to assess correlations between impaired contrast sensitivity and foveal shape we characterized the fovea in 48 Parkinson's disease patients and 45 control subjects by optical coherence tomography (OCT). The model quantifies structural changes in the fovea of Parkinson's disease patients that are correlated with a decline in contrast sensitivity. Retinal foveal remodeling may serve as a parameter for vision deficits in Parkinson's disease. Whether foveal remodeling reflects dopaminergic driven pathology or rather both dopaminergic and non-dopaminergic pathology has to be investigated in longitudinal studies.

Parkin is the most common causative gene in a cohort of mainland Chinese patients with sporadic early-onset Parkinson's disease.

INTRODUCTION: Genetic mutations associated with early-onset Parkinson's disease (EOPD) vary widely among different ethnicities. We detected the genes associated with EOPD in a Chinese cohort using next-generation sequencing (NGS) combined with multiplex ligation-dependent probe amplification (MLPA) and analyzed the phenotypic characteristics of the mutation carriers. METHODS: Cohort of 23 sporadic EOPD patients (onset age ≤ 45 years) were recruited. Genetic causes were identified by a targeted NGS panel containing 136 known extrapyramidal disease-causative genes. Multiplications or deletions of PD-causing genes were detected using the MLPA method. Demographic and clinical data were obtained, analyzed, and compared between patients with and those without Parkin gene variants. RESULTS: We identified 14 pathogenic or likely pathogenic variants (12 in Parkin, 1 in LRRK2, and 1 in VPS13C) in 10 patients (43.5%) and 8 rare variants of uncertain significance in 9 patients (39.1%). Parkin (34.8%) was the most common causative gene among our patients cohort, and exon deletion (62.5%) was the main type of variant. Patients with Parkin mutations had a younger age of onset, longer delay in diagnosis, slower disease progression, higher frequency of hyperreflexia, fatigue, and less hyposmia compared to patients without Parkin mutations. CONCLUSION: Our results revealed a higher prevalence of Parkin mutations in Chinese sporadic EOPD patients, and notably, exon deletion was the most common type of mutation. EOPD patients with Parkin mutations showed unique clinical characteristics.

Retinal single-layer analysis with optical coherence tomography (OCT) in schizophrenia spectrum disorder.

BACKGROUND: Volume reductions in brain structures of patients with schizophrenia spectrum disorder (SSD) have repeatedly been found in voxel-based morphometry MRI studies. Hence, an underlying neurodegenerative etiological component of SSD is currently being discussed. In recent years, the imaging method of optical coherence tomography (OCT) has shown its potential in evaluating structural changes in the retina in patients with confirmed neurodegenerative disorders, providing a window into the brain. METHODS: Twenty-six patients with schizophrenia or schizoaffective disorder and 23 age- and sex-matched healthy controls were examined with the Heidelberg Spectralis OCT system to derive a single-layer analysis of both retinas. The segmentation of retinal layers was manually corrected to minimize artifacts and software imprecisions. RESULTS: Compared to the control group, SSD patients showed reduced thickness and volume measurements for nearly all retinal layers, and these differences reached significance for macular volume, macular thickness, retinal nerve fiber layer (RNFL) and inner nucleiform layer (INL). Furthermore, a significant correlation between the duration of illness and the total volume of the RNFL was found. CONCLUSION: Our OCT measurements demonstrate reduced single retinal layer thickness in patients with SSD. In the context of the MRI volume changes, our results provide further evidence that structural changes seen in the brain of patients are also observable in the retina, potentially allowing further insights into the different components of the nervous system that are altered in this highly etiologically complex disorder.

Olfactory screening of Parkinson's Disease patients and healthy subjects in China and Germany: A study of cross-cultural adaptation of the Sniffin' Sticks 12-identification test.

BACKGROUND: Olfactory testing is a useful tool in the differential diagnosis of Parkinson's Disease (PD). Although fast and easy to use, the high intercultural variability of odor detection limits the world-wide use of the most common test sets. OBJECTIVE: The aim of this study was to test one of the most commonly used olfactory tests (Sniffin' Sticks 12-identification test) in an adapted version for a Chinese population of healthy subjects and PD patients. METHODS: For this purpose, cohorts of 39 Chinese and 41 German PD patients as well as 70 Chinese and 100 German healthy subjects have been examined both with the original and the adapted version of the Sniffin' Sticks test, the latter being designed according to the regional culture. RESULTS: The adapted Chinese version of the Sniffin' Sticks 12 identification test proved to discriminate Chinese PD patients from controls with a high specificity but relatively low sensitivity. Yet not all odor exchanges would have been necessary as the original odors including liquorice and coffee showed an equally high identification rate in the Chinese and German cohorts. CONCLUSIONS: The results showed that the newly adapted test could be used as a screening test for PD related olfactory dysfunction in a Chinese population. However further investigation will be necessary to optimize the selection of odors for the Chinese version of the test.

Analysis of CACNA1A CAG repeat lengths in patients with familial ALS.

Intermediate-length ATXN2 CAG repeats are a risk factor for amyotrophic lateral sclerosis (ALS). Here we report on a female patient with heterozygous repeat expansion mutation in the CACNA1A gene presenting with a pure ALS syndrome while her father, who also carries that CACNA1A mutation, suffers from a classical spinocerebellar ataxia type 6. Hypothesizing that CACNA1A CAG repeat expansions could be a monogenic cause for familial ALS (fALS), we analyzed the CAG repeat lengths in CACNA1A in a large cohort of genetically unexplained patients with fALS. Our results indicate that CAG repeat expansion mutations in CACNA1A are not a frequent monogenic cause of fALS but could phenotypically present as ALS in rare instances.

Acute DWI Reductions In Patients After Single Epileptic Seizures - More Common Than Assumed.

Background: Changes of cerebral diffusivity detected by magnetic resonance imaging (MRI) have been reported in epilepsy. Diffusion weighted imaging (DWI) detects changes in the distribution of water molecules by measuring the apparent diffusion coefficient (ADC) and is mainly used in the diagnosis of ischemic stroke. DWI changes in epilepsy were reported in status epilepticus (SE) or series of seizures. It remains unclear whether this phenomenon also occurs after single seizures. Accordingly, possible pathomechanisms have only been discussed on the presumed basis of ongoing epileptic brain activity. Methods: In this retrospective study, we systematically analyzed DWI alterations related to epileptic seizures in 454 patients who received MRI scanning within the first 24 h after seizure onset. Results: DWI restrictions not classified as ischemic stroke were observed in 18 patients (4%). We found DWI restrictions in 19% of patients with SE/seizure series and in 3% of patients after single focal and 2.5% after single generalized seizures. 17 patients with DWI alterations were diagnosed with a structural epilepsy. DWI signal decreased in the majority of patients within the first days and could not be detected in follow-up imaging >3 months. In all patients except one, DWI alterations were detected in the same hemisphere as the lesion. In the case of seizure series or SE, DWI restrictions mostly presented with a typical "garland-like" pattern alongside the cortical band or on the border of a defined lesion, while in isolated seizures, the restrictions were often rather subtle and small. Discussion: We show that DWI restrictions can be observed in patients after single epileptic seizures. As the vast majority of these patients was diagnosed with an epilepsy due to structural cerebral pathology, DWI restriction may reflect a higher vulnerability in these regions. This might also explain the fact that diffusivity changes were observed after single focal seizures as well as after multiple seizures or SE. The occurence itself on one side as well as the spatial pattern of this phenomenon on the other may thus not only be related to the duration of ictal activity, but to structural pathology.

Hyperconnective and hypoconnective cortical and subcortical functional networks in multiple system atrophy.

INTRODUCTION: In multiple system atrophy (MSA), the organization of the functional brain connectivity within cortical and subcortical networks and its clinical correlates remains to be investigated. METHODS: Whole-brain based 'resting-state' fMRI data were obtained from 22 MSA patients (11 MSA-C, 11 MSA-P) and 22 matched healthy controls, together with standardized clinical assessment and video-oculographic recordings (EyeLink®). RESULTS: MSA patients vs. controls showed significantly higher ponto-cerebellar functional connectivity and lower default mode network connectivity (p < .05, corrected). No differences were observed in the motor network and in the control network. The higher the ponto-cerebellar network functional connectivity was, the more pronounced was smooth pursuit impairment. CONCLUSION: This functional connectivity analysis supports a network-dependent combination of hyper- and hypoconnectivity states in MSA, in agreement with adaptive compensatory responses (hyperconnectivity) and a function disconnection syndrome (hypoconnectivity) that may occur in a consecutive sequence.

Retinal changes in patients with major depressive disorder - A controlled optical coherence tomography study.

BACKGROUND: Recent studies on the pathophysiology of major depression (MD) indicate that degenerative and inflammatory processes may play a role. This finding is supported by magnetic resonance imaging (MRI)-based meta-analysis that show volume reductions in circumscribed areas of the brain in patients with MD. Using optical coherence tomography (OCT), retinal changes have been demonstrated in neurodegenerative disorders. In light of this inflammatory/degenerative hypothesis, we tested whether patients with MD exhibit retinal alterations that might correlate with the severity and duration of the disease. METHODS: Patients with MD and age- and gender-matched healthy controls were recruited for the measurement of the total volume and thickness of their retina as well as the thicknesses and volumes of five different retinal layers using single-layer-analysis provided by the spectral-domain-OCT. RESULTS: OCT data from 28 patients with MD and 20 healthy controls were available for evaluation. The exploratory intra-individual group comparison of the two eyes showed a small but significant difference in the retinal total volume (right = 8.69mm3; left = 8.72mm3; p = 0.03) only in patients with MD. There were no other significant differences between the patients with MD and the healthy controls with respect to the OCT measurements. LIMITATIONS: The small group size as well as the absence of correction for multiple testing due to the exploratory design should be considered as limitations of our study. CONCLUSION: While retinal total volume differs between the eyes of patients with MD, the comparison of retinal parameters between these patients and age- and gender-matched healthy volunteers did not show any differences.

Regional microstructural damage and patterns of eye movement impairment: a DTI and video-oculography study in neurodegenerative parkinsonian syndromes.

Characteristic alterations of eye movement control are a common feature of neurodegenerative parkinsonism, including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). Regional microstructural alterations as assessed by diffusion tensor imaging (DTI) have been reported in PD, PSP, and MSA. Therefore, we investigated the specific association between eye movement disturbances and microstructural impairment in these diseases. Video-oculographic recordings of smooth pursuit and visually guided reactive saccades as well as fractional anisotropy (FA) maps computed from whole-brain DTI data were analyzed for 36 PD, 30 PSP, 18 MSA patients, and 23 matched healthy control subjects. In PSP, peak eye velocity was pathologically slowed compared to controls (p < 0.001) and correlated significantly with microstructural impairment in the midbrain (p < 0.001, corrected). Smooth pursuit eye movements were substantially disturbed in MSA mainly by characteristic 'catch-up' saccades resulting in significantly reduced pursuit gain (p < 0.001, corrected), and the shape of saccadized pursuit in MSA was significantly correlated with FA reductions in the middle cerebral peduncle (p < 0.001, FDR corrected). The prevalence of saccadic intrusions as a measure for inhibitory control was significantly increased in PD compared with controls (p < 0.001), but was uncorrelated with FA in cortical and subcortical white matter. Eye movement disturbances in PSP and MSA-but not in PD-are associated with diagnosis-specific regional microstructural alterations in the white matter. The non-invasive quantified oculomotor function analysis can give clues to the underlying structural connectivity network pathology and underpins its role as a technical marker in PSP and MSA.

A first approach to a neuropsychological screening tool using eye-tracking for bedside cognitive testing based on the Edinburgh Cognitive and Behavioural ALS Screen.

OBJECTIVE: Reliable assessment of cognitive functions is a challenging task in amyotrophic lateral sclerosis (ALS) patients unable to speak and write. We therefore present an eye-tracking based neuropsychological screening tool based on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a standard screening tool for cognitive deficits in ALS. METHODS: In total, 46 ALS patients and 50 healthy controls matched for age, gender and education were tested with an oculomotor based and a standard paper-and-pencil version of the ECAS. RESULTS: Significant correlation between both versions was observed for ALS patients and healthy controls in the ECAS total score and in all of its ALS-specific domains (all r > 0.3; all p < 0.05). The eye-tracking version of the ECAS reliably distinguished between ALS patients and healthy controls in the ECAS total score (p < 0.05). Also, cognitively impaired and non-impaired patients could be reliably distinguished with a specificity of 95%. CONCLUSION: This study provides first evidence that the eye-tracking based ECAS version is a promising approach for assessing cognitive deficits in ALS patients who are unable to speak or write.

Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism.

BACKGROUND: One common feature of neurodegenerative parkinsonism including Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) is altered eye movement control. Characteristic regional structural atrophy patterns in MRI can be observed in PD, MSA, and PSP. OBJECTIVE: To investigate the association between eye movement disturbances and regional brain atrophy in patients with PD, MSA, and PSP. METHODS: High-resolution 3-dimensional T1-weighted MRI images and video-oculographic recordings (EyeLink®) were obtained from 39 PD, 32 PSP, and 18 MSA patients and 24 matched healthy control subjects. Automatic regional volumetric assessment was performed using atlas-based volumetry (ABV). RESULTS: The prevalence of saccadic intrusions as a measure of inhibitory control was significantly increased in PD patients compared to controls (p < 0.001) and negatively correlated with whole brain volume, cerebral brain volume, and occipital lobe volume (p = 0.0057, p = 0.0049, and p = 0.0059, respectively; all p values are false discovery rate corrected). In MSA, smooth pursuit was disturbed by characteristic "catch-up" saccades (p < 0.001) and it was significantly correlated with cerebellar volume (p = 0.004) and pontine volume (p < 0.001). The hallmark of PSP was pathologically slowed vertical peak eye velocities (p < 0.001); the lower the peak eye velocity, the more marked midbrain atrophy (p = 0.007). CONCLUSIONS: Foci of regional atrophy correlated with disease-specific eye movement alterations in all investigated parkinsonian syndromes. Oculomotor impairment in PD, predominantly the result of executive dysfunction, was linked to cerebral atrophy. Impairment in the corresponding oculomotor pathways was associated with atrophy of pontocerebellar oculomotor structures in MSA and midbrain atrophy in PSP.

Manual MRI morphometry in Parkinsonian syndromes.

BACKGROUND: Several morphometric magnetic resonance imaging parameters may serve for differential diagnosis of parkinsonism. The objective of this study was to identify which performs best in clinical routine. METHODS: We acquired multicentric magnetization-prepared rapid gradient echo sequences in patients with Parkinson's disease (n=204), progressive supranuclear palsy (n=106), multiple system atrophy-cerebellar, (n = 21); multiple system atrophy-parkinsonian (n = 60), and healthy controls (n = 73), performed manual planimetric measurements, and calculated receiver operator characteristics with leave-one-out cross-validation to propose cutoff values. RESULTS: The midsagittal midbrain area was reduced in PSP versus all other groups (P < 0.001). The midsagittal pons area was reduced in MSA-cerebellar, MSA-parkinsonian, and PSP versus PD patients and healthy controls (P < 0.001). The midbrain/pons area ratio was lower in PSP (P < 0.001) and higher in MSA-cerebellar and MSA-parkinsonian versus PD and PSP (P < 0.001). CONCLUSIONS: The midsagittal midbrain area most reliably identified PSP, the midsagittal pons area MSA-cerebellar. The midbrain/pons area ratio differentiated MSA-cerebellar and PSP better than the magnetic resonance-Parkinson index. © 2017 International Parkinson and Movement Disorder Society.