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The evaluation of cognitive-communication disorders is performed with several types of assessment methods. These methods include different types of cognitive and language tests such as the Arizona Battery for Communication Disorders of Dementia (ABCD). The present study aimed to validate the ABCD in the Greek language. 132 individuals participated in the study: 60 adults in cognitive health (ACH) and 72 patients [24 Parkinson Disease (PD) patients without cognitive impairment, 24 with Parkinson Disease Dementia (PDD) and 24 with Alzheimer's Disease (AD)]. The cognitive and mental status of all participants was estimated by means of the Mini Mental State Examination (MMSE), the Abbreviated Mental Test Score (AMTS), the Clock Drawing Test (CDT), the Instrumental Activities of Daily Living (IADL), the Neuropsychiatric Inventory (H-NPI) the Geriatric Depression Scale -15 (GDS-15) and the ABCD. Statistically significant differences were found between all tests administered with the PDD and AD patients having the lower scores. The ABCD showed good psychometric properties, internal consistency (Cronbach alpha=0. 901) and discriminatory ability. It was significantly correlated with the AMTS, CDT, IADL, and MMSE.The Greek version of the ABCD demonstrated good validity, sensitivity, and discriminatory ability. The ABCD is a valuable instrument to assess cognitive-communication dis-orders.

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by cortical and subcortical atrophies, with early involvement of the hippocampus and amygdala. A 58-year-old man with clinical presentation of primary progressive aphasia-particularly its svPPA (semantic variant)-and bilateral asymmetric (left-predominant) anterior temporal lobe atrophy on MRI was referred for brain perfusion SPECT. This revealed bilateral hypoperfusion of the anterior temporal lobe (sustained by software-fused SPECT/MRI), pointing toward FTD rather than Alzheimer disease. Furthermore, voxel-based MRI volumetric analysis confirmed bilateral atrophy affecting the hippocampus and amygdala. Combining SPECT with MRI was supportive of the early-onset FTD-related svPPA diagnosis.

Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of grafts from patients with noncirrhotic inherited metabolic disorders may ultimately develop metabolic syndrome, and management is usually intricate, being complicated by the underlying initial disorder, other comorbidities, and post-transplantation conditions.We report here the management and the outcome in a patient with acquired transthyretin amyloidosis after DLT and significant comorbidities. Final treatment with a transthyretin gene silencing agent, patisiran, was well tolerated and resulted in remission of the aggravating neurological deficits in a follow-up period of 2 years.The case presented here supports the concept that patisiran can target the hepatocytes producing the mutated transthyretin in acquired transthyretin amyloidosis, as efficiently as in hereditary transthyretin amyloidosis (hATTR), and can be used to treat patients with transthyretin amyloidosis after DLT.

Background: Accurate assessment of symptoms in Parkinson’s disease (PD) is essential for optimal treatment decisions. During the past few years, different monitoring modalities have started to be used in the everyday clinical practice, mainly for the evaluation of motor symptoms. However, monitoring technologies for PD have not yet gained wide acceptance among physicians, patients, and caregivers. The COVID-19 pandemic disrupted the patients’ access to healthcare, bringing to the forefront the need for wearable sensors, which provide effective remote symptoms’ evaluation and follow-up. Case Report: We report two cases with PD, whose symptoms were monitored with a new wearable CE-marked system (PDMonitor(®)), enabling appropriate treatment modifications. Conclusion: Objective assessment of the patient’s motor symptoms in his daily home environment is essential for an accurate monitoring in PD and enhances treatment decisions.

Background Screening people's cognitive skills have been proven essential for reference to full assessment. These methods include short scales, such as the Abbreviated Mental Test Score (AMTS). The AMTS is a valid 10-item questionnaire that has been translated into many languages, but not in Greek yet. The aim of this study is the validation of the Greek version of the AMTS with an additional estimation of its cutoff scores. Methods About 132 individuals [60 controls and 72 patients (24 with Parkinson's disease (PD), 24 with Parkinson's disease dementia (PDD), and 24 with Alzheimer's disease (AD)] participated in this study. All participants besides the AMTS completed the Mini Mental State Examination (MMSE), the Tuokko's Clock Drawing Test (CDT), the Instrumental Activities of Daily Living (IADL), the Arizona Battery for Communication Disorders of Dementia (ABCD), the Hellenic versions of the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale (GDS-15). Results Statistically significant differences were found between all subgroups for the AMTS. The AMTS showed high internal consistency (Cronbach alpha = 0.819 and coefficient omega ω = 0.814). A threshold equal to 6.50 (AUC: 0.908, p = 0.000) between groups with and without cognitive impairment was calculated. The AMTS was significantly correlated with the CDT, IADL, and MMSE. Conclusion The proposed version of the AMTS can distinguish between groups with and without cognitive impairment. Additionally, the AMTS is found to be clinically valid having high reliability and classification accuracy. Conclusively, it is a valuable instrument for screening different types of cognitively impaired patients.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) represent two major chronic diseases that affect a large percentage of the population and share common pathogenetic mechanisms, including oxidative stress and inflammation. Considering their common mechanistic aspects, and given the current lack of effective therapies for AD, accumulating research has focused on the therapeutic potential of antidiabetic drugs in the treatment or prevention of AD.This review examines the latest preclinical and clinical evidence on the potential of antidiabetic drugs as candidates for AD treatment. Numerous approved drugs for T2DM, including insulin, metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium glucose cotransporter 2 inhibitors (SGLT2i), are in the spotlight and may constitute novel approaches for AD treatment.Among other pharmacologic agents, GLP-1 RA and SGLT2i have so far exhibited promising results as novel treatment approaches for AD, while current research has centered on deciphering their action on the central nervous system (CNS). Further investigation is crucial to reveal the most effective pharmacological agents and their optimal combinations, maximize their beneficial effects on neurons, and find ways to increase their distribution to the CNS.

The aim of this review is to summarize the current knowledge about clinical findings, diagnostic work-up, and treatment of uveomeningeal syndromes, with special emphasis on the uveitic features of these pathologies. A thorough literature search was performed in the PubMed database. An additional search was conducted in Google Scholar to complete the collected items. Uveomeningeal syndromes is an umbrella term for a group of pathologies that affect the uvea, retina, and meninges. They present with a plethora of clinical features ranging from meningitis and meningoencephalitis to uveitis. A wide spectrum of infectious, inflammatory, and neoplastic conditions have been associated with these clinical entities. However, these syndromes are probably an autoimmune and inflammatory disorder, as they mainly cause inflammation to the ocular and neurologic body structures. However, less frequently, infectious uveitis with concomitant acute or chronic meningoencephalitis can also lead to uveomeningeal syndrome. Primary vitreoretinal (and central nerve system) lymphoma, as well as paraneoplastic disorders, should also be part of the differential diagnosis, before diagnosing a case as uveomeningeal syndrome. The diagnostic approach in a patient with uveomeningeal syndrome can be extremely challenging. Thorough ophthalmic and medical history together with a detailed ophthalmic and systematic assessment forms the cornerstone of a holistic approach to these cases. A systematic algorithm is necessary for a methodical diagnostic and treatment approach, to organize an effective management plan for patients with uveomeningeal syndromes.

Summary Objective The inclusion of subjective methods for evaluating Voice Disorders is proven an essential factor for diagnosis as these methods include self-reported questionnaires (eg, Voice Handicap Index-VHI) for everyday clinical practice. In turn, by obtaining cut-off scores of self-perceived questionnaires intended for assessment procedures of different voice disorders (eg, patients with neurological problems), the clinicians might be helped toward finding their patients’ needs leading to better monitoring, and treatment suggestions. Consequently, the purpose of this study was to estimate the cut-off scores for the Greek VHI relevant to patients with neurogenic voice disorders. Methods Ninety subjects participated in this research. Sixty-six of them served as the control group while the remaining 24 patients exhibited Neurogenic Voice Disorders (eg, spasmodic dysphonia or vocal fold paralysis). They filled in the VHI and the Voice Evaluation Template. All participants were examined with the use of video laryngeal endoscopy and stroboscopy. Results The analysis revealed higher medians in all domains (of the VHI) for the patients compared to the control group. The cut-off points were estimated at the values of 24.50 (Total Score–AUC 0.932, P = 0.000), 9.00 (Functional Domain–AUC 0.917, P = 0.000), 10.00 (Physical Domain–AUC 0.948, P = 0.000), and 9.00 (Emotional Domain–AUC 0.830, P = 0.000). Conclusion The estimated cut-off scores are in agreement with previous studies. These scores could probably used to enhance therapeutic monitoring of patients who suffer from neurogenic voice disorders. This study underlines the importance of considering different cutoff points for individuals with voice disorders due to diverse neurogenic etiologies.

Background and Objective Parkinson's disease (PD) is a degenerative disorder of the central nervous system for which currently there is no cure. Its treatment requires long-term, interdisciplinary disease management, and usage of typical medications, including levodopa, dopamine agonists, and enzymes, such as MAO-B inhibitors. The key goal of disease management is to prolong patients' independence and keep their quality of life. Due to the different combinations of motor and non-motor symptoms from which PD patients suffer, in addition to existing comorbidities, the change of medications and their combinations is difficult and patient-specific. To help physicians, we developed two decision support models for PD management, which suggest how to change the medication treatment. Methods The models were developed using DEX methodology, which integrates the qualitative multi-criteria decision modelling with rule-based expert systems. The two DEX models differ in the way the decision rules were defined. In the first model, the decision rules are based on the interviews with neurologists (DEX expert model), and in the second model, they are formed from a database of past medication change decisions (DEX data model). We assessed both models on the Parkinson's Progression Markers Initiative (PPMI) and on a questionnaire answered by 17 neurologists from 4 European countries using accuracy measure and the Jaccard index. Results Both models include 15 sub-models that address possible medication treatment changes based on the given patients' current state. In particular, the models incorporate current state changes in patients' motor symptoms (dyskinesia intensity, dyskinesia duration, OFF duration), mental problems (impulsivity, cognition, hallucinations and paranoia), epidemiologic data (patient's age, activity level) and comorbidities (cardiovascular problems, hypertension and low blood pressure). The highest accuracy of the developed sub-models for 15 medication treatment changes ranges from 69.31 to 99.06 %. Conclusions Results show that the DEX expert model is superior to the DEX data model. The results indicate that the constructed models are sufficiently adequate and thus fit for the purpose of making “second-opinion” suggestions to decision support users.

Background Mobile health, predominantly wearable technology and mobile apps, have been considered in Parkinson disease to provide valuable ecological data between face-to-face visits and improve monitoring of motor symptoms remotely. Objective We explored the feasibility of using a technology-based mHealth platform comprising a smartphone in combination with a smartwatch and a pair of smart insoles, described in this study as the PD_manager system, to collect clinically meaningful data. We also explored outcomes and disease-related factors that are important determinants to establish feasibility. Finally, we further validated a tremor evaluation method with data collected while patients performed their daily activities. Methods PD_manager trial was an open-label parallel group randomized study.The mHealth platform consists of a wristband, a pair of sensor insoles, a smartphone (with dedicated mobile Android apps) and a knowledge platform serving as the cloud backend. Compliance was assessed with statistical analysis and the factors affecting it using appropriate regression analysis. The correlation of the scores of our previous algorithm for tremor evaluation and the respective Unified Parkinson’s Disease Rating Scale estimations by clinicians were explored. Results Of the 75 study participants, 65 (87%) completed the protocol. They used the PD_manager system for a median 11.57 (SD 3.15) days. Regression analysis suggests that the main factor associated with high use was caregivers’ burden. Motor Aspects of Experiences of Daily Living and patients’ self-rated health status also influence the system’s use. Our algorithm provided clinically meaningful data for the detection and evaluation of tremor. Conclusions We found that PD patients, regardless of their demographics and disease characteristics, used the system for 11 to 14 days. The study further supports that mHealth can be an effective tool for the ecologically valid, passive, unobtrusive monitoring and evaluation of symptoms. Future studies will be required to demonstrate that an mHealth platform can improve disease management and care. Trial Registration ISRCTN Registry ISRCTN17396879; http://www.isrctn.com/ISRCTN17396879 International Registered Report Identifier (IRRID) RR2-10.1186/s13063-018-2767-4

BACKGROUND Mobile health, predominantly wearable technology and mobile apps, have been considered in Parkinson disease to provide valuable ecological data between face-to-face visits and improve monitoring of motor symptoms remotely. OBJECTIVE We explored the feasibility of using a technology-based mHealth platform comprising a smartphone in combination with a smartwatch and a pair of smart insoles, described in this study as the PD_manager system, to collect clinically meaningful data. We also explored outcomes and disease-related factors that are important determinants to establish feasibility. Finally, we further validated a tremor evaluation method with data collected while patients performed their daily activities. METHODS PD_manager trial was an open-label parallel group randomized study.The mHealth platform consists of a wristband, a pair of sensor insoles, a smartphone (with dedicated mobile Android apps) and a knowledge platform serving as the cloud backend. Compliance was assessed with statistical analysis and the factors affecting it using appropriate regression analysis. The correlation of the scores of our previous algorithm for tremor evaluation and the respective Unified Parkinson’s Disease Rating Scale estimations by clinicians were explored. RESULTS Of the 75 study participants, 65 (87%) completed the protocol. They used the PD_manager system for a median 11.57 (SD 3.15) days. Regression analysis suggests that the main factor associated with high use was caregivers’ burden. Motor Aspects of Experiences of Daily Living and patients’ self-rated health status also influence the system’s use. Our algorithm provided clinically meaningful data for the detection and evaluation of tremor. CONCLUSIONS We found that PD patients, regardless of their demographics and disease characteristics, used the system for 11 to 14 days. The study further supports that mHealth can be an effective tool for the ecologically valid, passive, unobtrusive monitoring and evaluation of symptoms. Future studies will be required to demonstrate that an mHealth platform can improve disease management and care. INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-018-2767-4

Cognitive impairment is common in multiple sclerosis (MS), but deficits tend to be more pronounced in progressive MS, negatively impacting daily functional capacity. Despite this, most cognitive rehabilitation (CR) interventions to date have focused on relapsing-remitting MS (RRMS). Moreover, information on the efficacy of CR in progressive MS is limited and controversial. The present study investigated the efficacy of a home based, computer assisted cognitive rehabilitation (HBCACR) intervention (RehaComThis was a randomized, multi site, sham controlled trial. Thirty six (36) individuals with SPMS, naïve to the RehaCom software, with cognitive deficits were randomized to the treatment (IG; n= 19) or control group condition (CG; n=17). Treatment with the RehaCom modules consisted of 24 domain and task specific, 45 minute session's over an 8-week period, three sessions per week, applied by each patient at home. The CG completed non specific computer based activities at home with the same frequency and duration. Primary cognitive outcome measures included the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, and secondary outcome measures for depression (BDI-FS), fatigue (MFIS), and quality of life (EuroQol EQ-5D) visual analogue scale (VAS).The two groups were well matched on demographic and clinical characteristics, cognitive reserve and severity of cognitive deficits at baseline assessment. At post treatment assessment the IG group showed significant improvements with large effect sizes; in verbal learning [z = -4.759, p.0005, g = 2.898], visuospatial memory [z = -3.940, p.0005, g = 1.699] and information processing speed [z= -4.792, p.0005, g = 2.980], compared with the sham control group. We also found significant between group differences on physical [z=-3.308, p = .001, g= -.604], cognitive [z = -4.011, p.0005, g = -1.654], psychosocial [z= 3.308, p = .010, g = -.940], and general fatigue impact [z= -2.623, p = .008, g = -.519], depression severity [z = -2.730, p = .006, g = -.519], and quality of life [z= -4.239, p.0005, g = -1.885] in favor of the treated group.These data provide the first evidence supporting the efficacy of computer based restorative cognitive rehabilitation applied at home exclusively in SPMS patients, suggesting that adaptive neuroplasticity may occur after functional cognitive training in progressive MS. Improved cognitive functioning in combination with mood augmentation appear to have ameliorated fatigue, which impacted daily functioning activity and culminated in improved health related quality of life.

BACKGROUND AND PURPOSE This study aimed was to measure the quality of life, fatigue, stress, and depression in a consecutive sample of caregivers of multiple sclerosis (MS) patients. METHODS We included data from 131 consecutive caregivers of MS patients [age=51.2±12.8 years (mean±SD), males=53.4%, duration of caregiving=10.0±6.3 years]. We assessed the quality of life, fatigue, stress, and depression of the caregivers using the 36-item Short Form Health Survey, Krupp Fatigue Severity Scale, Kingston Caregiver Stress Scale, and Hamilton Scale for Depression, respectively. The disability status of the patients was assessed using the Kurtzke Expanded Disability Status Scale. We used linear regression models to identify possible correlations between all of the aforementioned scales, while multivariable logistic regression models were employed to assess the correlations of caregiver fatigue with caregiver characteristics and patient disability. RESULTS The linear regression analyses revealed that caregiver fatigue was positively associated with stress and negatively correlated with both physical health status and mental health status. Caregiver stress was positively associated with depression and negatively correlated with both physical health status and mental health status. Depression was negatively correlated with both caregiver physical health status and mental health status. In multivariable logistic regression analysis, caregiver fatigue was found to be independently associated with education status [odds ratio (OR)=0.61, 95% CI=0.37 to 0.99], history of chronic disease (OR=5.52, 95% CI=1.48 to 20.55), other chronic diseases in the family (OR=7.48, 95% CI=1.49 to 37.47), and the disability status of the patient (OR=1.36, 95% CI=1.03 to 1.80). CONCLUSIONS Fatigue, stress, and depression in caregivers of MS patients are negatively correlated with their physical health status and mental health status. Caregiver fatigue is independently associated with education status, history of chronic disease, other chronic disease in the family, and patient disability.

Objective We performed a systematic review and meta-analysis to evaluate the proposed association of restless legs syndrome (RLS) with cerebrovascular/cardiovascular outcomes. Methods We calculated the corresponding odds ratios on the prevalence of cerebrovascular/cardiovascular risk factors and standardized mean differences on the reported mean age at baseline between RLS patients and controls. We also calculated the corresponding risk ratios and adjusted for potential confounders hazard ratios (HRsadjusted) on the reported outcomes of interest between RLS patients and controls. Results We identified 8 eligible studies (644 506 patients, mean age: 60.2 years, 36.2% males; 3.3% with RLS). RLS patients were found to have significantly higher prevalence of hypertension (P = .002), diabetes (P = .003) and hyperlipidemia (P = .010) compared to controls. In the unadjusted analyses of prospective observational studies, RLS patients were found to have significantly higher risk for cerebrovascular ischaemia (P = .01) and all-cause mortality (P = .04) compared to controls during follow-up, while in the adjusted for potential confounders analyses RLS patients were only found to have a higher risk of all-cause mortality (HR adjusted=1.52, 95% CI: 1.17-1.97, P = .002). Conclusions The present report does not provide evidence for an increased risk of cerebrovascular and cardiovascular events in RLS patients, which highlights the vast presence of confounding factors.

The recent advances of Brain Computer Interfaces (BCI) systems, can provide effective assistance for real time prognosis systems for patients who suffered from epileptic seizures. This paper presents an EEG classification strategy for short-term epilepsy prognosis, using software for Brain-Computer Interface (BCI) systems. A training scenario is presented, where significant features are extracted and a classification algorithm is trained. The training procedure extracts knowledge in terms of a classification model, which is employed in a real-time testing. For the training of the classification scenario a five-classes dataset of EEG signals is employed in which two-classes have been recorded extracranially and the rest three intracranially including one class with epileptic seizure activity and two classes with seizure-free signals. Promising quantitative results are reported.

Epilepsy is a chronic neurological disorder characterized by recurrent, sudden discharges of cerebral neurons, called seizures. Seizures are not always clearly defined and have extremely varied morphologies. Neurophysiologists are not always able to discriminate seizures, especially in long-term EEG datasets. Affecting 1% of the worlds population with 1/3 of the epileptic patients not corresponding to anti-epileptic medication, epilepsy is constantly under the microscope and systems for automated detection of seizures are thoroughly examined. In this paper, a method for automated detection of epileptic activity is presented. The Discrete Wavelet Transform (DWT) is used to decompose the EEG recordings in several subbands and five features are extracted from the wavelet coefficients creating a set of features. The extracted feature vector is used to train a Support Vector Machine (SVM) classifier. Five classification problems are addressed, reaching high levels of overall accuracy ranging from 87% to 100%.

BACKGROUND AND PURPOSE: Histopathologic studies have demonstrated WM damage in primary Sjögren syndrome. The purpose of this study was to evaluate WM microstructural changes by use of DTI-derived parameters in patients with primary Sjögren syndrome. MATERIALS AND METHODS: DTI was performed in 19 patients with primary Sjögren syndrome (age, 64.73 ± 9.1 years; disease duration, 11.5 ± 7.56 years) and 16 age-matched control subjects. Exclusion criteria were a history of major metabolic, neurologic, or psychiatric disorder and high risk for cardiovascular disease. Data were analyzed by use of tract-based spatial statistics, for which the WM skeleton was created, and a permutation-based inference with 5000 permutations was used with a threshold of P < .01, corrected for multiple comparisons to enable identification of abnormalities in fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. RESULTS: Tract-based spatial statistics showed decreased fractional anisotropy in multiple areas in patients with primary Sjögren syndrome compared with control subjects, located mainly in the corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus. Increased mean diffusivity and radial diffusivity and decreased axial diffusivity were observed in most of the fiber tracts of the brain in patients with primary Sjögren syndrome, compared with control subjects. CONCLUSIONS: Patients with primary Sjögren syndrome show loss of WM microstructural integrity, probably related to both Wallerian degeneration and demyelination.

To compare the effects of botulinum toxin injection with and without needle electromyographic guidance for the treatment of spasticity.A randomized controlled study was conducted in a tertiary university hospital. Twenty-seven adult hemiplegic patients with spasticity due to brain or spinal cord damage were included. Spastic muscles were injected with botulinum toxin with or without EMG guidance. The modified Ashworth scale and modified Barthel index in each patient pre- and post-injection were documented.In group A, which consisted of 15 patients (55.55%), the injection was administered with needle electromyographic guidance, while in 12 patients (44.44%) of group B without electromyographic guidance with the use of anatomic landmarks only. The follow-up period was 3 months. At 3 weeks post-injection, spasticity was decreased (p 0.05) in all patients and the mean (SD) reduction of spasticity was higher (p 0.05) in group A (1.67 (0.5)) than group B (1.25 (0.46)). Similarly, the mean (SD) functional modified Barthel index improved statistically significantly (p 0.001) post-injection (45.37 (8.43)) than pre-injection (54.07 (9.610), especially in group A (p 0.05).The effectiveness of intramuscular botulinum toxin injection for the treatment of spasticity in hemiplegic patients is superior when performed with needle electromyographic guidance than without electromyography.It is recommended that botulinum toxin muscle injections of hemiplegic limbs be performed with EMG guidance More spasticity reduction and functional improvement at 3 months post-injection was observed in patients injected with botulinum toxin by the use of combined EMG guidance and anatomic landmarks EMG guidance might also save amount of botulinum toxin due to less spasticity observed during injection than when injection is performed with anatomic landmarks only.

The present study prospectively investigated the value of free-running electromyography (EMG) and transcranial motor-evoked potentials (TcMEP) during anterior cervical microdiscectomy and fusion for cervical disc herniation with radiculopathy. Thirty-eight patients were eligible for inclusion in the study. Pain was assessed using the visual analogue scale (VAS) score. Quality of life results were scored according to Odom's criteria in the postoperative period. Patients with at least a 41% increase in TcMEP amplitude had an excellent postoperative outcome. When the increase of TcMEP amplitude was ⩽ 11% the patient's outcome was fair. The VAS score decreased from a preoperative mean value of 6.39 ± 2.16 to a 3-month postoperative value of 2.39 ± 1.17. At 12-month follow-up the mean VAS score was 1.65 ± 0.90. TcMEP and free-running EMG are effective for monitoring the spinal cord during surgery and may hold an additional prognostic role.

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., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND AND PURPOSE Multiple system atrophy (MSA) is a progressive neurodegenerative disorder divided into a parkinsonian (MSA-P) and a cerebellar variant. The purpose of this study was to assess regional brain atrophy and iron content using Voxel-based morphometry (VBM) and Voxel-based relaxometry (VBR) respectively, in MSA-P. METHODS Using biological parametric mapping the effect of brain atrophy was evaluated in T2 relaxation time (T2) measurements by applying analysis of covariance (ANCOVA) and correlation analysis to the VBM and VBR data. Eleven patients with MSA-P (aged 61.9 ± 11.7 years, disease duration 5.42 ± 2.5 years) and 11 controls were studied. RESULTS In comparison to the controls the patients showed decreased gray matter in the putamen, the caudate nuclei, the thalami, the anterior cerebellar lobes, and the cerebral cortex, and white matter atrophy in the pons, midbrain, and peduncles. VBR analysis showed prolonged T2 in various cortical regions. On ANCOVA, when controlling for gray and white matter volume, these regions of prolonged T2 were shrunk. Negative correlation was demonstrated between T2 and gray and white matter volume. CONCLUSIONS Diffuse brain atrophy, mainly in the motor circuitry is observed in MSA-P. Normalization for atrophy should always be performed in T2 measurements.

Motor dysfunction produced by the chronic non-physiological stimulation of dopaminergic receptors on striatal medium spiny neurons is associated with alterations in the sensitivity of glutamatergic receptors, including those of the N-methyl-D-aspartate (NMDA) subtype. Functional characteristics of these ionotropic receptors are regulated by their phosphorylation state. Lesioning the nigrostriatal dopamine system of rats induces parkinsonian signs and increases the phosphorylation of striatal NMDA receptor subunits on serine and tyrosine residues. The intrastriatal administration of certain inhibitors of the kinases capable of phosphorylating NMDA receptors produces a dopaminomimetic motor response in these animals. Treating parkinsonian rats twice daily with levodopa induces many of the characteristic features of the human motor complication syndrome and further increases the serine and tyrosine phosphorylation of specific NMDA receptor subunits. Again, the intrastriatal administration of selective inhibitors of certain serine and tyrosine kinases alleviates the motor complications. NMDA receptor antagonists, including some non-competitive channel blockers, act both palliatively and prophylactically in rodent and primate models to reverse these levodopa-induced response alterations. Similarly, in clinical studies dextrorphan, dextromethorphan, and amantadine have been found to be efficacious against motor complications. Recent observations in animal models further indicate that certain amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonists alleviate, while others exacerbate, these complications. Thus, it appears that the denervation or intermittent stimulation of striatal dopaminergic receptors differentially activates signal transduction pathways in medium spiny neurons. These in turn modify the phosphorylation state of ionotropic glutamate receptors and consequently their sensitivity to cortical input. These striatal changes contribute to symptom production in Parkinson's disease, and their prevention or reversal could prove useful in the treatment of this disorder.