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This expert working group report proposes an updated approach to subtype definition of vascular parkinsonism (VaP) based on a review of the existing literature. The persistent lack of consensus on clear terminology and inconsistent conceptual definition of VaP formed the impetus for the current expert recommendation report. The updated diagnostic approach intends to provide a comprehensive tool for clinical practice. The preamble for this initiative is that VaP can be diagnosed in individual patients with possible prognostic and therapeutic consequences and therefore should be recognized as a clinical entity. The diagnosis of VaP is based on the presence of clinical parkinsonism, with variable motor and non-motor signs that are corroborated by clinical, anatomic or imaging findings of cerebrovascular disease. Three VaP subtypes are presented: (1) The acute or subacute post-stroke VaP subtype presents with acute or subacute onset of parkinsonism, which is typically asymmetric and responds to dopaminergic drugs; (2) The more frequent insidious onset VaP subtype presents with progressive parkinsonism with prominent postural instability, gait impairment, corticospinal, cerebellar, pseudobulbar, cognitive and urinary symptoms and poor responsiveness to dopaminergic drugs. A higher-level gait disorder occurs frequently as a dominant manifestation in the clinical spectrum of insidious onset VaP, and (3) With the emergence of molecular imaging biomarkers in clinical practice, our diagnostic approach also allows for the recognition of mixed or overlapping syndromes of VaP with Parkinson's disease or other neurodegenerative parkinsonisms. Directions for future research are also discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care., Methods: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39., Results: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%)., Conclusions: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Advanced Parkinson's disease (APD) is characterized by increased functional disability, caused by motor complications, the presence of axial symptoms, and emergent disease- and drug-related non-motor symptoms. One of the advanced therapies available is intrajejunal infusion of levodopa/carbidopa intestinal gel (LCIG); however, patient selection for this treatment is sometimes difficult, particularly because of overlapping indications with other alternatives. In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment), a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.

Purpose: The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients., Methods: Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification., Results: The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p < 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p < 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP., Conclusion: PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression.

The P3 can arguably be named the most intensely studied ERP. In spite of more than 40 years of research, fundamental questions regarding the nature of its neural generators remain unresolved. While most studies conclude that the P3 is a true classical "endogenous" potential, and that its surface potential distribution remains constant across sensory modalities, these results are largely based on low-density EEG recordings, without the use of high-resolution methods such as the spherical spline Laplacian (SSL). Seventeen healthy participants performed a three-stimulus oddball task in visual and auditory modality while their EEG was recorded using a 128-channel system. Comparison of amplitude-normalized SSL estimated P3 brain-surface potentials, and analysis of spatial and temporal correlations revealed significant differences between visual and auditory evoked P3 topographies from target and distractor stimuli (but not target minus frequent or distractor minus frequent comparisons). Based on these results, we postulate the likely existence of at least some sensory modality-specific neuronal generators of the P3., (© 2016 Society for Psychophysiological Research.)

Background: Dystonia is a movement disorder with patterned, directional, and often sustained muscle contractions that produce abnormal postures or repetitive movements. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and safe treatment for medically refractory dystonia. However, recent studies reported gait problems, gait freezing and falls in patients treated with DBS. Because these symptoms may point to deficient gait initiation processes, we systematically assessed the anticipatory postural adjustments (APAs) prior to stepping in dystonia patients with GPi-DBS., Methods: Thirteen patients with focal/segmental dystonia under GPi-DBS and twelve healthy control subjects were included in the study. Data were collected using pressure sensitive sensors and APAs were studied by centre of pressure measures. We compared APAs of both groups and analysed the influence of GPi-DBS on APAs in patients., Results: Medio-lateral and antero-posterior COP displacements, total COP path, maximal APA velocity and 1st step length were all smaller in patients for both ON (p=0.006, p=0.018, p=0.002, p=0.016, p=0.04) and OFF (p=0.001, p=0.01, p=0.001, p=0.03, p=0.024) condition compared to healthy subjects. GPi-DBS did not change APA parameters in patients., Conclusions: Observations that APAs are impaired in dystonia and are at the same time not affected by the stimulation current are compatible with the assumption that APAs and dystonic symptoms may rely on distinct networks, possibly within the same cortical and basal ganglia structures. With no effect of stimulation on APAs it is unlikely that this would be a mechanism of impaired balance in the patients after the surgery., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Mild cognitive impairment (MCI) affects the cognitive performance of elderly adults. However, the level of severity is not high enough to be diagnosed with dementia. Previous research reports subtle language impairments in individuals with MCI specifically in domains related to lexical meaning. The present study used both off-line (grammaticality judgment) and on-line (lexical decision) tasks to examine aspects of lexical processing and how they are affected by MCI. 21 healthy older adults and 23 individuals with MCI saw complex pseudo-words that violated various principles of word formation in Slovenian and decided if each letter string was an actual word of their language. The pseudo-words ranged in their degree of violability. A task effect was found, with MCI performance to be similar to that of healthy controls in the off-line task but different in the on-line task. Overall, the MCI group responded slower than the elderly controls. No significant differences were observed in the off-line task, while the on-line task revealed a main effect of Violation type, a main effect of Group and a significant Violation × Group interaction reflecting a difficulty for the MCI group to process pseudo-words in real time. That is, while individuals with MCI seem to preserve morphological rule knowledge, they experience additional difficulties while processing complex pseudo-words. This was attributed to an executive dysfunction associated with MCI that delays the recognition of ungrammatical formations.

Objective: Deep brain stimulation of the globus pallidus internus (GPi-DBS) is an efficient and safe treatment for medically refractory dystonia. However, recent studies reported gait problems, falls and bradykinesia in patients after the DBS procedure. The aim of this study was to quantify the effect of GPi-DBS on postural performance in patients with cranio-cervical dystonia., Methods: Thirteen patients with focal/segmental dystonia and GPi-DBS participated in the study. We performed two postural tests (pull test and push and release test) in on- and off-stimulation conditions and recorded the movements of the patients with inertial sensors., Results: Under stimulation patients exhibited a higher number of steps (p=0.015), reduced first step length (p=0.011) and lower stepping velocity (p=0.001), compared to off stimulation. We observed a higher number of steps in the push and release test compared to the pull test (p=0.038). The interaction between stimulation condition and test type was significant (p=0.027)., Conclusions: The velocity and amplitude of postural reactions are compromised by GPi-DBS in patients with cranio-cervical dystonia., Significance: This information corresponds to patient's reports of falls and postural instability after GPi-DBS. Pre-operatively, patients should be informed about the possibility of the occurrence of such phenomena., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Parkinson's disease (PD) patients show signs of cognitive impairment, such as executive dysfunction, working memory problems and attentional disturbances, even in the early stages of the disease. Though motor symptoms of the disease are often successfully addressed by dopaminergic medication, it still remains unclear, how dopaminergic therapy affects cognitive function. The main objective of this study was to assess the effect of dopaminergic medication on visual and auditory attentional processing. 14 PD patients and 13 matched healthy controls performed a three-stimulus auditory and visual oddball task while their EEG was recorded. The patients performed the task twice, once on- and once off-medication. While the results showed no significant differences between PD patients and controls, they did reveal a significant increase in P3 amplitude on- vs. off-medication specific to processing of auditory distractors and no other stimuli. These results indicate significant effect of dopaminergic therapy on processing of distracting auditory stimuli. With a lack of between group differences the effect could reflect either 1) improved recruitment of attentional resources to auditory distractors; 2) reduced ability for cognitive inhibition of auditory distractors; 3) increased response to distractor stimuli resulting in impaired cognitive performance; or 4) hindered ability to discriminate between auditory distractors and targets. Further studies are needed to differentiate between these possibilities., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The most frequently seen types of tremor are essential (ET) and parkinsonian tremor (PT) and in some patients clinical characteristics of these tremor types overlap. It is vital to distinguish between these two types of tremor in order to reach the right diagnosis and select the appropriate treatment. One of the widely used methods for tremor detection and discrimination, appropriate for a quick ambulatory assessment of the patient's tremor, is spirography. With spirography, the tremor can be observed through several parameters, for example, tremor spectrum and spiral image, which give useful information for its identification. Standard spirography parameters of ET and PT can overlap; therefore, these parameters are often not enough for identification of the observed tremor. To increase the specificity and sensitivity of spirography for PT, ET and normal, tremor free controls, we used the wavelet analysis with Morlet wavelet transform. To facilitate analysis, comparison, storage, and retrieval of spirography tremor records we also developed an integrated computer assisted spirography system that increases the convenience of outpatient tremor identification and follow-up. We conclude that wavelet analysis of spirography records increases the sensitivity and specificity of the method, thus, facilitating the distinction between ET and PT.

The aim of study was to assess cognition in patients with late onset depression in a symptom-free remission period measuring event-related potentials and reaction times (RT) in a modified computer version of the Stroop test. Thirty four patients with late-onset depression were included after they had reached remission. They were compared to age-, gender- and education-matched healthy controls. Each participant completed a single item computer version of the Stroop Color-word task using verbal response mode. EEG and RT were simultaneously recorded. RTs were significantly prolonged in patients in all conditions of the Stroop paradigm, and the interference effect was significantly greater in patients compared to controls. Results also revealed abnormal late positive Stroop related potentials in the period of about 500-600 ms period corresponding to the so-called P300b wave. Our study supports the view that patients with late onset depression are also cognitively impaired and that this impairment persists in the period of early remission. Using more sensitive ERP measurement of the Stroop task we demonstrated impaired information processing at an earlier, pre-response related stage., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: The paper describes the use of expert's knowledge in practice and the efficiency of a recently developed technique called argument-based machine learning (ABML) in the knowledge elicitation process. We are developing a neurological decision support system to help the neurologists differentiate between three types of tremors: Parkinsonian, essential, and mixed tremor (comorbidity). The system is intended to act as a second opinion for the neurologists, and most importantly to help them reduce the number of patients in the "gray area" that require a very costly further examination (DaTSCAN). We strive to elicit comprehensible and medically meaningful knowledge in such a way that it does not come at the cost of diagnostic accuracy., Materials and Methods: To alleviate the difficult problem of knowledge elicitation from data and domain experts, we used ABML. ABML guides the expert to explain critical special cases which cannot be handled automatically by machine learning. This very efficiently reduces the expert's workload, and combines expert's knowledge with learning data. 122 patients were enrolled into the study., Results: The classification accuracy of the final model was 91%. Equally important, the initial and the final models were also evaluated for their comprehensibility by the neurologists. All 13 rules of the final model were deemed as appropriate to be able to support its decisions with good explanations., Conclusion: The paper demonstrates ABML's advantage in combining machine learning and expert knowledge. The accuracy of the system is very high with respect to the current state-of-the-art in clinical practice, and the system's knowledge base is assessed to be very consistent from a medical point of view. This opens up the possibility to use the system also as a teaching tool., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Motor fluctuations and dyskinesia in later stages of Parkinson's disease (PD) are caused by pharmacokinetic as well as pharmacodynamic factors, intermittent dopaminergic stimulation being one of the most important. In the healthy brain, dopamine neurons in the substantia nigra pars compacta fire tonically at a steady rate of about 4 cycles/second. In later stages of PD, steady firing is replaced by pulsatile stimulation which causes molecular and physiologic changes in the basal ganglia. Continuous dopaminergic stimulation has been shown to dramatically improve motor fluctuations and dyskinesia by modifications of oral treatment (dopamine agonists, smaller, more frequent levodopa doses, controlled-release formulation of levodopa, addition of agents that slow down the catabolism of dopamine, such as inhibitors of catechol-O-methyl transferase and monoamine oxidase), transdermal delivery (rotigotine), infusion therapies (intravenous levodopa, subcutaneous application of apomorphine and lisuride, duodenal infusion of levodopa) and deep brain stimulation of the subthalamic nucleus.