Vascular Parkinsonism Patients Research Articles

The clinical and neuroimaging differences between vascular parkinsonism and Parkinson's disease: a case-control study.

Parkinson's disease (PD) and vascular parkinsonism (VaP) have highly overlapping phenotypes, and different prognosis. This study comprehensively investigated the clinical, brain MRI and transcranial sonography differences between VaP and PD. Forty-eight patients with PD, 27 patients with VaP, and 29 healthy controls were compared. All patients were assessed using the MDS-UPDRS, Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), Time Up and Go Test, and Non-Motor Symptoms Scale. Beck Depression Inventory, PD questionnaire- 39, international urine incontinence scale, cognitive assessment scales, MRI brain and transcranial colour-coded doppler. The study was registered on clinical-Trial.gov (NCT04308135) on 03/12/2020. VaP patients showed significantly older age of onset, shorter disease duration, lower drug doses and levodopa responsiveness, higher On and Off axial scores, On and Off BBS, higher On scores for PIGD, rigidity, bradykinesia and total motor MDS-UPDRS, lower On and Off tremor, lower-half predominance, lower asymmetrical presentation and symmetric index than PD patients. VaP patients had worse non-motor symptoms Scale (NMSS) than controls except for perceptual problems/hallucinations but better symptoms than PD patients except for urinary dysfunction. Quality of life (QoL) was impaired in VaP patients and was correlated with motor function and NMSs. The VaP group had significantly higher white matter lesions and brain atrophy, with lower hyperechogenicity of the substantia nigra and more impaired cerebral vascular resistance and vasoreactivity than the PD group. VaP has a characteristic motor and non-motor profile, with impaired QoL, white matter, and transcranial sonography abnormalities that differentiate it from PD. Further studies are warranted to explore the role of vascular lesions in the pathogenesis of VaP. The registered identifier NCT04308135 on clinical-Trial.gov. Registered on 03/12/2020.

Characterizing gait and exploring neuro-morphometry in patients with PSP-Richardson's syndrome and vascular parkinsonism

Gait differentiation in progressive supranuclear palsy (PSP) and vascular parkinsonism (VaP) is sometimes difficult to detect with the naked eye. Here, we compared specific gait parameters, neuro-morphometric indices, and their associations between patients with PSP Richardson's syndrome (PSP-RS) and VaP. A total of 18 PSP-RS and 13 VaP patients were recruited. Spatio-temporal gait parameters (GAITRite®) and neuroanatomical morphometry (FreeSurfer pipeline) were assessed. The groups were compared using unpaired t-tests involving 10000 random permutations after statistically controlling for total UPDRS-III and H&Y scores. Statistically significant differences between the groups were decided at < 5% Benjamini-Hochberg False Discovery Rate (FDR) for multiple-comparison related corrections. Spearman's correlations were performed to assess the significant associations (p < 0.05) between the gait parameters and morphometry indices. Among all the spatio-temporal gait parameters, PSP-RS patients displayed greater stride time, step time, swing time, and stance time variabilities compared to VaP. Morphometric analyses showed that thalamus, and caudate volumes were significantly lower, but cerebellar cortex, hippocampus, amygdala, accumbens, and putamen volumes were higher in PSP-RS than VaP. Moreover, the bilateral insula was significantly thinner in VaP than in PSP-RS. Correlation analyses support the involvement of limbic structures besides cerebellum in postural control during self-paced walking of PSP-RS patients. Our findings underline the importance of examining individual brain regions to understand the association of cortical and subcortical morphometric estimates and gait variability parameters in PSP-RS and VaP. This study suggests the involvement of the limbic system in addition to the classical neural structures for motor control and gait.

Olfactory Bulb Volume, Olfactory Sulcus Depth in Parkinson's Disease, Atypical Parkinsonism.

About 70-90% of Parkinson's disease (PD) patients have olfactory deficits which is considered as pre-motor symptom of PD. Lewy bodies have been demonstrated in the olfactory bulb (OB) in PD. To assess the OB volume (OBV), olfactory sulcus depth (OSD) in PD and compare with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and vascular parkinsonism (VP) patients and determine the cut-off volume of OB that will aid in the diagnosis of PD. This was a cross-sectional, hospital based, single-center study. Forty PD, 20 PSP, 10 MSA, 10 VP patients and 30 controls were recruited. OBV and OSD was assessed using 3-T magnetic resonance imaging (MRI) brain. Olfaction was tested using Indian Smell Identification test (INSIT). The mean total OBV in PD was 113.3 ± 79.2 mm3 and 187.4 ± 65.0 mm3 in controls (P = 0.003) which was significantly lower in PD. The mean total OSD in PD was 19.4 ± 8.1 and 21.1 ± 2.2 mm in controls (P = 0.41) with no difference. The mean total OBV was significantly lower in PD as compared to that of PSP, MSA and VP patients. There was no difference in the OSD among the groups. The total OBV in PD had no association with age at onset, duration of disease, dopaminergic drugs dosage, motor and non-motor symptoms severity but had positive correlation with cognitive scores. OBV is reduced in PD patients as compared to PSP, MSA, VP patients and controls. OBV estimation by MRI adds to the armamentarium in the diagnosis of PD.

Abstract TP208: A Novel Rat Model Of Vascular Parkinsonism Using The Vasoconstrictor Endothelin-1

Background: Vascular parkinsonism (VP) results from one or more small strokes in the basal ganglia. Patients with vascular parkinsonism usually are unaware of the individual strokes that occur, until progressive motor symptoms gradually appear. While Parkinson’s Disease (PD) and VP share some common symptoms, patients with VP show clear evidence of cerebrovascular disease, are likely to be older, more likely to present with gait difficulty rather than tremor, and less likely to respond to the use of levodopa compared with patients with PD. There is currently no clinically effective treatment for this condition and no rodent model established in the field to study VP. Methods: To stimulate the onset of VP, male Sprague Dawley rats (10-12 mos) were injected with the vasoconstrictor endothelin-1 (ET-1) into the dorsolateral striatum (DLS) or sham operation. Adhesive-tape removal test (ART) was used to test sensory-motor function at 2- and 5- days post DLS stroke and brains were removed and stained with TTC to assess the location of the infarct. In another set, animals were tested for apomorphine-induced rotational behavior at 21-28 days, in conjunction with immunohistochemistry to assess dopamine loss in the substantia nigra pars compacta. Results: We observed a discrete infarct localized to the DLS in animals injected with ET-1. There was no difference in latency to remove the tape in ART outcomes of ET-1 injected animals at 2- and 5- day post ischemia when compared to sham, consistent the fact that these coordinates resulted in a discrete striatal infarction, rather than a cortico-striatal infarction, which is seen in the ET1-induced middle cerebral artery stroke model in rats. At 21- and 28- days post, there was minimal rotational behavior and minimal loss of tyrosine hydroxylase (TH)-positive cells in the lesioned hemisphere, unlike that of the 6-OHDA model of PD, where rapid changes are seen in rotational behavior and loss of TH-positive cells. Conclusions: These data suggest that ET-1-mediated ischemia into the DLS is a promising model for the slow progression of dopaminergic loss and motor deficits reminiscent to that seen in VP patients. Apomorphine induced rotations and TH immunohistochemistry will be evaluated at 30-, 60- and 90- day timepoints.

Connectivity Alterations in Vascular Parkinsonism: A Structural Covariance Study

This study aimed to investigate the structural covariance between the striatum and large-scale brain regions in patients with vascular parkinsonism (VP) compared to Parkinson’s disease (PD) and control subjects, and then explore the relationship between brain connectivity and the clinical features of our patients. Forty subjects (13 VP, 15 PD, and 12 age-and-sex-matched healthy controls) were enrolled in this study. They each underwent a careful clinical and neuropsychological evaluation, DAT-SPECT scintigraphy and 3T MRI scan. While there were no differences between PD and VP in the disease duration and severity, nor in terms of the DAT-SPECT evaluations, VP patients had a reduction in structural covariance between the bilateral corpus striatum (both putamen and caudate) and several brain regions, including the insula, thalamus, hippocampus, anterior cingulate cortex and orbito-frontal cortex compared to PD and controls. VP patients also showed lower scores on several neuropsychological tests. Interestingly, in the VP group, structural connectivity alterations were significantly related to cognitive evaluations exploring executive functions, memory, anxiety and depression. This compelling evidence suggests that structural disconnection in the basal ganglia circuits spreading in critical cortical regions may be involved in the pathophysiology of cognitive impairment in VP.

Pain in atypical parkinsonism, vascular parkinsonism, and Parkinson's disease.

Pain is a common symptom in Parkinson's disease (PD) and is considered a pre-motor symptom suggesting sensory involvement in the pre-motor stage. Pain in other parkinsonian disorders such as atypical parkinsonism and vascular parkinsonism (VP) has been investigated in only a few studies. The characteristics of pain in other parkinsonian disorders, including the temporal relationships between pain and motor symptoms, were investigated in the present study. A total of 236 PD, 42 multiple system atrophy (MSA), 31 progressive supranuclear palsy (PSP), and 38 VP patients were screened for pain. After excluding patients with dementia and pain not related to PD, the presence of pain, severity, onset, type, and location were compared among the four patient groups. Difference was not observed in pain presence (χ2 = 3, p = 0.186), severity (F = 1.534, p = 0.207), or type (χ2 = 6, p = 0.400) among the four groups. However, the temporal relationship between pain and motor symptoms differed (H(3) = 8.764, p = 0.033). Pain predated motor symptoms in PD, MSA, and VP but often followed motor symptoms in PSP. The pain location in the body was different among the four patient groups (χ2 = 21, p = 0.018), and leg involvement was more common in PSP. The present study results suggest that pain can be a pre-motor symptom in PD, MSA, and VP but not in PSP, implying different pain pathogeneses in these disorders. Pain locations were other for each group, which requires further investigation with a more extensive study cohort.

Discrimination of idiopathic Parkinson’s disease and vascular parkinsonism based on gait time series and the levodopa effect

Idiopathic Parkinson’s disease (IPD) and vascular parkinsonism (VaP) present highly overlapping phenotypes, making it challenging to distinguish between these two parkinsonian syndromes. Recent evidence suggests that gait assessment and response to levodopa medication may assist in the objective evaluation of clinical differences. In this paper, we propose a new approach for gait pattern differentiation that uses convolutional neural networks (CNNs) based on gait time series with and without the influence of levodopa medication. Wearable sensors positioned on both feet were used to acquire gait data from 14 VaP patients, 15 IPD patients, and 34 healthy subjects. An individual’s gait features are affected by physical characteristics, including age, height, weight, sex, and walking speed or stride length. Therefore, to reduce bias due to intersubject variations, a multiple regression normalization approach was used to obtain gait data. Recursive feature elimination using the linear support vector machine, lasso, and random forest were applied to infer the optimal feature subset that led to the best results. CNNs were implemented by means of various hyperparameters and feature subsets. The best CNN classifiers achieved accuracies of 79.33%±6.46, 82.33%±10.62, and 86.00%±7.12 without (off state), with (on state), and with the simultaneous consideration of the effect of levodopa medication (off/on state), respectively. The response to levodopa medication improved classification performance. Based on gait time series and response to medication, the proposed approach differentiates between IPD and VaP gait patterns and reveals a high accuracy rate, which might prove useful when distinguishing other diseases related to movement disorders.

The pattern of FP-CIT PET in pure white matter hyperintensities–related vascular parkinsonism

ObjectivesTo determine whether vascular parkinsonism (VaP) patients with visually normal dopamine transporter (DAT) scans have presynaptic dopaminergic depletion. MethodsWe enrolled 23 VaP patients who had parkinsonism, relevant diffuse subcortical white matter hyperintensities (WMH), and visually normal DAT scans, 23 Parkinson's disease (PD) patients, and 31 control subjects. By quantitatively analyzing 18F–N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography, we compared the pattern of striatal DAT availability among groups. The discriminatory power of striatal DAT availability to differentiate VaP patients from control subjects or PD patients was assessed using receiver operating characteristics (ROC) analyses. Additionally, correlation analysis was performed to determine whether WMH severity or Unified Parkinson Disease Rating Scale Part III (UPDRS-III) score is related to presynaptic dopaminergic depletion in VaP. ResultsVaP patients exhibited decreased DAT availability in all striatal subregions, including posterior putamen, compared to control subjects. VaP patients and control subjects had similar patterns of anteroposterior and ventrodorsal DAT gradients in caudate and putamen level, but VaP patients exhibited significantly different patterns at putamen level, relative to PD patients. The severity of periventricular WMH was significantly correlated with all substriatal DAT availability in VaP, but not with UPDRS-III scores. The ROC analysis showed that DAT availability in caudate and posterior putamen had a fair discriminatory power when differentiating VaP patients from control subjects. ConclusionsThis study demonstrates that VaP patients with WMH exhibited diffusely decreased DAT availability without any specific regional gradients of DAT patterns distinct from either control subjects or PD patients.

A Case of Idiopathic Normal Pressure Hydrocephalus Presenting as Vascular Parkinsonism

Idiopathic normal pressure hydrocephalus (iNPH) is the most common form of hydrocephalus in adults. It is characterized by dilated ventricles and the Hakim triad, which consists of gait disturbance, cognitive impairment, and urinary incontinence. The gold standard treatment for iNPH is shunting, but frequent lumbar punctures (LPs) are helpful for diagnosis and predicting shunting outcome and is considered the treatment of choice when shunting is not available. One condition with similar presentation to iNPH is Vascular parkinsonism (VP), which is characterized by an established relationship between cerebrovascular diseases and the clinical symptoms of Parkinson’s disease (PD). VP patients usually present with lower-body parkinsonism, including impaired gait, instability, difficulty with maintaining gait, and frequent episodes of freezing. VP is managed by levodopa followed by transcranial magnetic stimulation then vitamin D. LPs are less effective for VP than iNPH. Our case report shows that iNPH may be misdiagnosed with VP. Here we present a case of a 71-year-old male with a history of previous lacunar strokes who was admitted for possible vascular parkinsonism. Eight months prior to coming to the hospital, he developed gait disturbances; and four months later, he developed urinary symptoms. Upon examination, his gait initiation was hesitant, wide-based, and magnetic with decreased arm swing. The patient scored 20 out of 30 points on the Montreal Cognitive Assessment. The only cranial nerve involvement was a diminished gag reflex. Brain magnetic resonance imaging revealed symmetrically enlarged ventricles with mildly dilated sulci. Routine laboratory testing was normal. Two months of treatment with levodopa did not improve his symptoms but draining 50 mL of cerebrospinal fluid (CSF) has dramatically improved his gait. A final diagnosis of iNPH was therefore made. To conclude, iNPH and VP are two manageable diseases but the differential diagnosis between them is particularly challenging due to similar clinical and neuroradiological features. We suggest further studies to establish supporting guidelines by using neuroradiological or neurophysiological biomarkers which may help physicians in ameliorate diagnostic accuracy between the two entities.

Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases.

Neurodegenerative diseases (NDs) are age-dependent; among them, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent. Similarly, cerebrovascular damage can induce the development of vascular-related disorders that share common features with AD and PD, respectively, named vascular dementia (VD) and vascular parkinsonism (VP). To date, ND diagnosis is mainly clinical; therefore, since these disorders show similar symptoms, their correct discrimination may be difficult. We detected 23 ND-associated microRNAs (miRNAs) by literature mining and investigated their serum expression in a cohort of 139 patients including AD, PD, VD, and VP patients and healthy controls. TaqMan RT-PCR data showed that miR-23a upregulation was associated with an ongoing neurodegenerative process, similar to miR-22* and miR-29a, while let-7d, miR-15b, miR-24, miR-142-3p, miR-181c, and miR-222 showed an altered expression in Parkinson-like phenotypes, as well as miR-34b, miR-125b, and miR-130b in Alzheimer-like disorders. By computing logistic regression models and ROC curves, we identified signatures of neuro-miRNAs specific for each disease, showing good diagnostic performance. Interestingly, we found that miR-23a, miR-29a, miR-34b, and miR-125b exhibited a different distribution between exosomes and vesicle-free serum, suggesting a heterogeneity of secretion for these miRNAs. Our results suggest that miRNA signatures could discriminate in a non-invasive manner neurodegenerative disorders, thus improving clinical diagnoses.

Gait stride-to-stride variability and foot clearance pattern analysis in Idiopathic Parkinson’s Disease and Vascular Parkinsonism

The literature on gait analysis in Vascular Parkinsonism (VaP), addressing issues such as variability, foot clearance patterns, and the effect of levodopa, is scarce. This study investigates whether spatiotemporal, foot clearance and stride-to-stride variability analysis can discriminate VaP, and responsiveness to levodopa.Fifteen healthy subjects, 15 Idiopathic Parkinson's Disease (IPD) patients and 15 VaP patients, were assessed in two phases: before (Off-state), and one hour after (On-state) the acute administration of a suprathreshold (1.5 times the usual) levodopa dose. Participants were asked to walk a 30-meter continuous course at a self-selected walking speed while wearing foot-worn inertial sensors. For each gait variable, mean, coefficient of variation (CV), and standard deviations SD1 and SD2 obtained by Poincaré analysis were calculated. General linear models (GLMs) were used to identify group differences. Patients were subject to neuropsychological evaluation (MoCA test) and Brain MRI.VaP patients presented lower mean stride velocity, stride length, lift-off and strike angle, and height of maximum toe (later swing) (p < .05), and higher %gait cycle in double support, with only the latter unresponsive to levodopa. VaP patients also presented higher CV, significantly reduced after levodopa. Yet, all VaP versus IPD differences lost significance when accounting for mean stride length as a covariate.In conclusion, VaP patients presented a unique gait with reduced degrees of foot clearance, probably correlated to vascular lesioning in dopaminergic/non-dopaminergic cortical and subcortical non-dopaminergic networks, still amenable to benefit from levodopa. The dependency of gait and foot clearance and variability deficits from stride length deserves future clarification.

Comparative evaluation of non-motor displays of the parkinson's disease and vascular parkinsonism

The purpose of the research: To conduct a comparative analysis of the frequency and nature of the non-motor manifestations of Parkinson's disease (PD) and vascular parkinsonism (VP).&#x0D; Material and Methods. The research was carried out in 153 patients with Parkinson's disease (PD) and 69 patients with vascular parkinsonism (VP). Clinical and neurological studies, assessment of the severity of emotional disorders using g scale HADS, cognitive function was examined by the scale MMSE.&#x0D; Results. Autonomic disturbances were observed in 2.5 times more likely in patients with PD and 85% in patients with VP, they were observed by us in 30% of patients. Among autonomic dysfunctions in patients with PD, the most frequently observed general hyperhidrosis, voiding, and constipation. . In patients with VP autonomic disorders occurred less often than patients with PD, however, the severity and frequency of occurrence of orthostatic hypotension was higher in VP compared with PD. Among emotional disorders in PD one of the most frequent was a depressive syndrome. It was observed in 58.8% of patients, while in the group with vascular parkinsonism its frequency was 30.4%. Level of depression of HADS in PD was statistically higher than VP patients. Cognitive impairment developed in both groups, approximately at the same percentage of cases; however, the degree of cognitive impairment was higher in the group of patients with VP.

Magnetic resonance parkinsonism index in progressive supranuclear palsy and vascular parkinsonism

To investigate accuracy of the magnetic resonance parkinsonism index (MRPI) in differentiating progressive supranuclear palsy (PSP) from vascular parkinsonism (VP). We retrospectively analyzed radiological data of 12 PSP patients and 17 VP patients group-matched by age and sex who performed a standardized brain magnetic resonance imaging (MRI). Analysis of selected structures morphometry was performed to all study subjects and the MRPI was calculated for each selected patient. MRI midbrain area as well as superior cerebellar peduncle width were significantly lower in PSP patients compared to VP subjects. MRPI was significantly larger in PSP patients compared to VP subjects. MRPI value ≥13 distinguished the two groups with a sensitivity of 100% (95% CI 69.9-100) and a specificity of 100% (95% CI 77.1-100). MRPI may represent an accurate tool in differentiating PSP from VP.

COMPARATIVE EVALUATION OF NON-MOTOR DISPLAYS OF THE PARKINSON'S DISEASE AND VASCULAR PARKINSONISM

The purpose of the research: To conduct a comparative analysis of the frequency and nature of the non-motor manifestations of Parkinson's disease (PD) and vascular parkinsonism (VP). Material and Methods. The research was carried out in 153 patients with Parkinson's disease (PD) and 69 patients with vascular parkinsonism (VP). Clinical and neurological studies, assessment of the severity of emotional disorders using g scale HADS, cognitive function was examined by the scale MMSE. Results. Autonomic disturbances were observed in 2.5 times more likely in patients with PD and 85% in patients with VP, they were observed by us in 30% of patients. Among autonomic dysfunctions in patients with PD, the most frequently observed general hyperhidrosis, voiding, and constipation. . In patients with VP autonomic disorders occurred less often than patients with PD, however, the severity and frequency of occurrence of orthostatic hypotension was higher in VP compared with PD. Among emotional disorders in PD one of the most frequent was a depressive syndrome. It was observed in 58.8% of patients, while in the group with vascular parkinsonism its frequency was 30.4%. Level of depression of HADS in PD was statistically higher than VP patients. Cognitive impairment developed in both groups, approximately at the same percentage of cases; however, the degree of cognitive impairment was higher in the group of patients with VP.

Characterization of gastrointestinal disorders in patients with parkinsonian syndromes.

This study was aimed to investigate gastrointestinal (GI) dysfunction in patients with Parkinson's disease (PD) compared with those in patients with other parkinsonian disorders, and to characterize parkinsonian motor and non-motor correlates for GI dysfunction. Consecutive patients with PD, atypical parkinsonism (P-plus) and vascular parkinsonism (VP) were enrolled in this multicenter systematic survey. Data for weight loss, appetite loss, sialorrhea, dysphagia, gastroesophageal reflux disease (GERD) and constipation were simultaneously collected using symptom-specific, structured questionnaires. For the PD group, information for onset age, PD duration, anti-parkinsonian drug dosages, unified PD rating scale, and Hoehn & Yahr stage were collected at the time of the interview. Enrolled in the study were 329 PD, 82P-plus, and 62 VP patients. GI symptom frequencies were similar in PD and other parkinsonian groups. Among the PD patients, constipation was the most common symptom, followed by appetite loss, weight loss, dysphagia, sialorrhea, and GERD (64.9%, 45.4%, 35.7%, 19.4%, 15.0%, and 9.6%, respectively). Dysphagia, sialorrhea, and constipation became more frequent with more advanced PD stages. Cognition, sleep and mood disturbances were significantly associated with weight loss, appetite loss, and dysphagia, whereas bradykinesia, axial and postural instability with gait disturbance were associated with dysphagia. GI disturbance is common in patients with non-PD parkinsonism as well as in those with PD. GI symptoms correlated with distinct parkinsonian motor and nonmotor features in PD. Further studies are warranted to reveal the pathophysiological mechanisms and prognostic features of GI disturbances in parkinsonian disorders.

Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

Kinematic analysis of 24-hour recording of walking pattern in patients with vascular parkinsonism

Background: There is a need to define the basic characteristics of various kinematic parameters recorded during walking in patients with vascular parkinsonism (VP). The present study was designed to determine the kinematic features of walking in VP patients. For this purpose, gait acceleration and gait cycle were recorded continuously over 24-h period of daily living in VP patients, patients with Parkinson's disease (PD), and healthy subjects. Methods: We used our newly developed 24-h monitoring device, the portable gait rhythmogram, which records gait during walking, and computes gait-induced accelerations with pattern matching algorithm. We studied nine VP patients with history of multiple lacunar infarcts (mean age ± standard deviation (SD): 72.6 ± 5.0 years, 7 men), 39 PD patients (mean age ± SD: 70.8 ± 5.8 years, 18 women), and 15 normal control subjects (mean age ± SD: 67.9 ± 4.7 years, 9 men). Results: The “amount of overall movements per 24 h” was lower in VP and PD, compared with the control, with no significant differences between the two groups. Gait acceleration during walking was significantly lower (p < 0.01 in each case), while the gait cycle was the same in VP and PD patients compared with the control. Conclusions: The results suggest that deficit in force production and preservation of gait rhythm are common features of walking patterns in VP and PD patients.

Characterization of cerebral microbleeds in idiopathic Parkinson's disease.

Cerebral microbleeds (CMBs) have been extensively studied in healthy controls and patients with cerebrovascular disease and Alzheimer's disease. Our aim was to characterize the clinical and radiological features of CMBs in idiopathic Parkinson's disease (IPD). This cross-sectional study included consecutive parkinsonian patients who attended the authors' movement disorders clinic from March 2010 to February 2012 and underwent a standard magnetic resonance imaging (MRI) protocol with gradient recalled echo taken with a 3 T MRI machine. Amongst parkinsonian disorders, CMBs were most common in vascular parkinsonism (VP) (56%) and least common in IPD (17.7%). In IPD, CMBs were significantly associated with white matter hyperintensities and concurrent lacunar infarctions. The presence of CMBs had no effect on various cognitive domains in IPD. IPD with CMBs was discriminated from VP by clinical and neuroimaging findings: frequencies of motor subtypes were similar between IPD with and without CMBs, whereas all VP patients were the postural-instability gait difficulty type. In 90.9% of the IPD cases with CMBs, the numbers of CMBs were three or less, whereas the numbers of CMBs exceeded three in 50% of the cases of VP and exceeded 10 in 31.3% of the cases (P < 0.001). The topography of the CMBs in IPD was also different from that in VP (P < 0.01). Cerebral microbleeds are not rare in IPD, and IPD with CMBs does not appear to be a form of VP. Further studies in larger populations are needed to elucidate the clinical implications of CMBs in terms of prognoses and cognitive changes in IPD.

The relationship of leukoaraiosis and the clinical severity of vascular Parkinsonism

Vascular Parkinsonism (VP) is referred to as secondary Parkinsonian syndrome. It occurs with lacunar state or sub-cortical white matter micro-angiopathy and is highly associated with vascular risk factors and leukoaraiosis, also known as cerebral white matter lesions (WML). This study aimed to assess the prevalence of different vascular risk factors and WML in patients with VP, and their impact on clinical features. Sixty-two consecutive VP patients (70.2±9.2years) were evaluated for clinical severity using the Unified Parkinson's Disease Rating Scale (UPDRS). WML was assessed and scored on fluid-attenuated inversion recovery T2-weighted (FLAIR) magnetic resonance imaging (MRI). Cerebro-vascular risk factors, WML severity, and the UPDRS for clinical disability were analyzed statistically. There were no associations between WML score and age, sex, hypertension, diabetes, previous stroke, cardiac disease, cigarette smoking, or serum levels of cholesterol and triglyceride. The WML score positively correlated with UPDRS part I (p=0.035) and part III (p=0.041) scores. After adjustments for age, gender, stroke history, and use of levodopa, the WML score was associated with the UPDRS total (p=0.020), part I (p=0.012), part II (p=0.039), and part III (p=0.019) scores. The severity of WML is not associated with conventional vascular risk factors in VP patients but is significantly correlated with the UPDRS total and all sub-scores, which suggests that disruption of the cortico-sub-cortical circuits may lead to impaired mentation, behavior and mood, activities of daily living, and motor performance in these patients.

Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [(123)I]FP-CIT SPECT.

The study's objective was to develop diagnostic predictive models using data from two commonly used [(123)I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [(123)I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [(123)I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [(123)I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [(123)I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. The predictive models built with ROI data and SPM data from [(123)I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres.