Combined central and peripheral demyelination - one-year follow-up of patient with co-incidence of multiple sclerosis and multifocal acquired demyelinating sensory and motor neuropathy - A Case Report.

Combined central and peripheral demyelination (CCPD) is a rare autoimmune neurologic disease, characterized by immune-mediated damage of myelin sheath at central and peripheral levels of the nervous system. The current knowledge about this disorder is only limited, mainly due to the low incidence of the disease. According to previous studies, CCPD has a very heterogeneous course, insufficient therapeutic response, and an unfavorable prognosis. We report on the 37-year-old patient with a coincidence of demyelinating lesions in the brain fulfilling current McDonald's diagnostic criteria for multiple sclerosis, as well as the presence of an atypical variant of chronic inflammatory demyelinating polyneuropathy (CIDP) - multifocal acquired demyelinating sensory-motor neuropathy (MADSAM), as a subtype of combined central and peripheral demyelination (CCPD).

Factors associated with psychiatric and physical comorbidities in bipolar disorder: a nationwide multicenter cross-sectional observational study.

Background: Bipolar disorder (BD) is a chronic and disabling affective disorder with significant morbidity and mortality. Despite the high rate of psychiatric and physical health comorbidity, little is known about the complex interrelationships between clinical features of bipolar illness and comorbid conditions. The present study sought to examine, quantify and characterize the cross-sectional associations of psychiatric and physical comorbidities with selected demographic and clinical characteristics of adults with BD. Methods: A nationwide multicenter cross-sectional observational epidemiological study conducted from October 2015 to March 2017 in Slovakia. Results: Out of 179 study participants [median age 49 years (interquartile range IQR 38-58); 57.5% females], 22.4% were free of comorbidity, 42.5% had both psychiatric and physical comorbidities, 53.6% at least one psychiatric comorbidity, and 66.5% at least one physical comorbidity. The most prevalent were the essential hypertension (33.5%), various psychoactive substance-related disorders (21.2%), specific personality disorders (14.6%), obesity (14.5%), and disorders of lipoprotein metabolism (14%). The presence of an at least one physical comorbidity, atypical symptoms of BD, and unemployed status were each associated with an at least one psychiatric comorbidity independent of sex, early onset of BD (age of onset <35 years), BD duration and pattern of BD illness progression (p < 0.001). The presence of various psychoactive substance-related disorders, BD duration, atypical symptoms of BD, unemployed status, pension, female sex, and not using antipsychotics were each associated with an at least one physical comorbidity independent of the pattern of BD illness progression (p < 0.001). In several other multiple regression models, the use of antipsychotics (in particular, olanzapine) was associated with a decreased probability of the essential hypertension and predicted the clinical phenotype of comorbidity-free BD (p < 0.05). Conclusion: This cross-national study has reported novel estimates and clinical correlates related to both the comorbidity-free phenotype and the factors associated with psychiatric and physical comorbidities in adults with BD in Slovakia. The findings provide new insights into understanding of the clinical presentation of BD that can inform clinical practice and further research to continue to investigate potential mechanisms of BD adverse outcomes and disease complications onset.

Brain volume loss in multiple sclerosis is independent of disease activity and might be prevented by early disease-modifying therapy.

INTRODUCTION: Neurodegeneration is likely to be present from the earliest stages of multiple sclerosis (MS). MS responds poorly to disease-modifying treatments (DMTs) and leads to irreversible brain volume loss (BVL), which is a reliable predictor of future physical and cognitive disability. Our study aimed to discover the relationship between BVL, disease activity, and DMTs in a cohort of patients with MS. MATERIAL AND METHODS: A total of 147 patients fulfilled our inclusion criteria. Relevant demographic and clinical data (age, gender, time of MS onset, time of treatment initiation, DMT characteristics, Expanded Disability Status Scale (EDSS), number of relapses in the last two years prior to MRI examination) were correlated with MRI findings. RESULTS: Patients with progressive MS had significantly lower total brain and grey matter volumes (p = 0.003; p < 0.001), and higher EDSS scores (p < 0.001), compared to relapsing-remitting patients matched by disease duration and age. There was no association between MRI atrophy and MRI activity (c2 = 0.013, p = 0.910). Total EDSS negatively correlated with the whole brain (rs = -0.368, p < 0.001) and grey matter volumes (rs = -0.308, p < 0.001), but was not associated with the number of relapses in the last two years (p = 0.278). Delay in DMT negatively correlated with whole brain (rs = -0.387, p < 0.001) and grey matter volumes (rs = -0.377, p < 0.001). Treatment delay was connected with a higher risk for lower brain volume (b = -3.973, p < 0.001), and also predicted a higher EDSS score (b = 0.067, p < 0.001). CONCLUSIONS: Brain volume loss is a major contributor to disability progression, independent of disease activity. Delay in DMT leads to higher BVL and increased disability. Brain atrophy assessment should be translated into daily clinical practice to monitor disease course and response to DMTs. The assessment of BVL itself should be considered a suitable marker for treatment escalation.

Tolcapone improves outcomes in patients with Parkinson disease treated by levodopa/carbidopa intestinal gel: A pilot study.

BACKGROUND: Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage. OBJECTIVE: The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone-as an add-on therapy to LCIG in patients with PD-on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters. METHODS: We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment. RESULTS: The level of HCY increased among patients without treatment (4.95 ± 12.54), and decreased in the vitamin (-17.73 ± 11.82) and tolcapone groups (-8.81 ± 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (-0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089). CONCLUSION: Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL.

ASXL3 De Novo Variant-Related Neurodevelopmental Disorder Presenting as Dystonic Cerebral Palsy.

ASXL3 loss-of-function variants represent a well-established cause of Bainbridge-Ropers syndrome, a syndromic neurodevelopmental disorder with intellectual and motor disabilities. Although a recent large-scale genomics-based study has suggested an association between ASXL3 variation and cerebral palsy, there have been no detailed case descriptions. We report, here, a female individual with a de novo pathogenic c.1210C > T, p.Gln404* nonsense variant in ASXL3, identified within the frame of an ongoing research project applying trio whole-exome sequencing to the diagnosis of dystonic cerebral palsy. The patient presented with a mixture of infantile-onset limb/trunk dystonic postures and secondarily evolving distal spastic contractures, in addition to more typical features of ASXL3-related diseases such as severe feeding issues, intellectual disability, speech impairment, and facial dysmorphic abnormalities. Our case study confirms a role for ASXL3 pathogenic variants in the etiology of cerebral-palsy phenotypes and indicates that dystonic features can be part of the clinical spectrum in Bainbridge-Ropers syndrome. ASXL3 should be added to target-gene lists used for molecular evaluation of cerebral palsy.

Psychiatric and somatic co-morbidities in patients with Parkinson's disease: A STROBE-compliant national multi-center, cross-sectional, observational study COSMOS in Slovakia.

OBJECTIVE: Co-morbidities in any disorder can complicate its diagnostic process, they require more complex clinical management and lead to worse health outcomes and increased healthcare costs. There are regional differences in the prevalence of specific co-morbidities in Parkinson's disease (PD), and data from middle Europe are lacking. The project COSMOS aimed to disclose the prevalence of co-morbidities among patients with PD in Slovakia. METHODS: In a national, multi-center, cross-sectional, observational study, neurologists gathered relevant demographical and clinical data aimed at all psychiatric and somatic co-morbidities. RESULTS: From overall 737 patients, 51.00 % had at least one psychiatric co-morbidity, the most prevalent were depressive episode/recurrent depressive disorder (26.05%), sleep disorders (23.20%), dementia (13.16%), and neurotic, stress-related, and somatoform disorders (11.53%). In addition, 92.9 % had at least one somatic co-morbidity, the most prevalent were hypertensive diseases (67.71%), ischemic heart diseases (42.74%), diseases of the musculoskeletal system, and connective tissue (39.21), and disorders of lipoprotein metabolism (33.24%). The number of psychiatric co-morbidities increased with PD progression; the prevalence of somatic comorbidities increased also with the age (p<0.001 in all cases). CONCLUSION: This study with a large cohort of PD patients confirmed a high prevalence of depression, dementia, sleep problems, and anxiety disorders, together with cardiovascular disorders, diseases of the musculoskeletal system, and metabolic syndrome. With PD progression, the number of both psychiatric and somatic co-morbidities is on the increase. If not treated properly, they lead to more complicated management. That's why it's essential to search for any co-morbidity to provide patients with early and adequate therapy to avoid further worsening of quality of life.

Levodopa-Carbidopa Intestinal Gel Improves Symptoms of Orthostatic Hypotension in Patients with Parkinson's Disease-Prospective Pilot Interventional Study.

Parkinson's disease (PD) is currently considered progressive neurodegeneration of both the central and peripheral nervous systems. Widespread neuropathological changes lead to a complex clinical presentation with typical motor (hypokinesia, tremor, and rigidity) and various nonmotor symptoms. Orthostatic hypotension is one of the most disabling nonmotor features contributing to increased morbidity and mortality and decreased quality of life (QoL). Our study aimed to disclose the effect of a continuous infusion of levodopa-carbidopa intestinal gel (LCIG) on symptoms of orthostatic hypotension. Nine patients indicated for LCIG and eight matched patients on optimized medical treatment (OMT) were examined with scales for orthostatic symptoms (SCOPA-AUT), nonmotor symptoms and motor fluctuations (MDS-UPDRS), and QoL (PDQ39) at both baseline and after six months. The scores of "light-headedness after standing" and "fainting" decreased in the LCIG group compared to the OMT group. Treatment with LCIG was associated with a significantly higher decrease in the score of "light-headedness after standing". Change in the PDQ39 correlated positively with fluctuation improvement and with change in the scores of both "light-headedness" and "fainting". LCIG treatment improved symptoms of orthostatic hypotension in patients with PD mainly by a reduction in motor complications. Decreased severity in both motor and nonmotor fluctuations was connected also with improved QoL. Continuous treatment with LCIG should be considered not only in the case of severe motor fluctuation but also in patients with nonmotor fluctuations responsive to dopaminergic treatment.

Effect of Pillbox Organizers with Alarms on Adherence to Pharmacotherapy in Parkinson Disease Patients Taking Three and More Daily Doses of Dopaminergic Medications.

Improvement of adherence to pharmacotherapy in patients with Parkinson's disease (PD) is a challenge in routine clinical practice. Our study was aimed at the effect of pillbox organizers with alarms improving adherence to pharmacotherapy and its impact on clinical outcomes. Forty nonadherent patients with PD being treated with ≥ 3 daily doses of levodopa and/or dopamine agonists were pseudorandomized and consecutively ranked to groups A (early-start intervention) and B (delayed-start intervention). We used the following validated diagnostic instruments: MMAS-8 (adherence), PDQ-8 (quality of life, QoL), GDS (depression), NMSS (non-motor symptoms), MDS-UPDRS III (motor involvement), MDS-UPDRS IV, and WOQ-9 (motor and non-motor fluctuations and dyskinesias). We proved a significantly improved rate of adherence with the use of pillbox organizers with alarms. Moreover, after only four weeks of using the pillbox organizer, we detected an improvement in QoL scores, motor involvement, motor-, and non-motor fluctuations. Our study showed that pillbox organizers with alarms are efficient in improving adherence to pharmacotherapy in PD. It also could contribute to better motor states, less severe fluctuations, and improved QoL.

Monogenic variants in dystonia: an exome-wide sequencing study.

BACKGROUND: Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. METHODS: For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. FINDINGS: We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. INTERPRETATION: In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. FUNDING: Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

Gait Disorders Questionnaire-Promising Tool for Virtual Reality Designing in Patients With Parkinson's Disease.

Background: Gait disorders (GD) are frequent and disabling symptoms in patients with Parkinson's disease, mostly because they significantly limit mobility and often lead to fear of falls or actual falls. Nowadays, rehabilitation is considered to be the most effective nonpharmacological approach to reduce risk of falls. Using paradigms in virtual reality (VR) is a promising tool in neurorehabilitation because of the potential improvement in motor learning and improvement in daily functioning by replicating everyday real-life scenarios. Objective: To identify the most prevalent everyday situations which impair gait in PD that could be simulated in virtual reality (VR) environment. Methods: A newly developed self-report questionnaire consisting of 15 binary response items (YES/NO) encompassing everyday walking situations was administered to 62 patients diagnosed with idiopathic PD according to MDS Clinical Diagnostic Criteria. We included patients able to walk unassisted for at least 10 min and without significant cognitive impairment. Mokken Scale Analysis was used to evaluate psychometric properties of the scale. Results: Questionnaires from 58 patients were analyzed (31 men, age = 63 ± 9.9 y, disease duration = 7.02 ± 4.03 y, LEDD = 1115 ± 549.4 mg, H&Y = 2.4 ± 0.6). Only 10 items (out of 15) were identified as scalable and these were included in Gait Disorders Questionnaire (GDQ). The most prevalent trigger of gait disorders was walking under time pressure, followed by gait in crowded places and walking while dual-tasking. The total score of GDQ significantly correlated with the disease duration (r s = 0.347, p = 0.008) and modified H&Y staging (r s = 0.288, p = 0.028). Conclusion: With the use of GDQ we identified the most prevalent everyday transition activities that provoke gait disorders in patients with PD. The results may be useful for further development and systematic application of VR paradigms for physiotherapy of PD patients.

Adherence to Pharmacotherapy in Patients With Parkinson's Disease Taking Three and More Daily Doses of Medication.

Background: Once-daily treatment formulation is associated with better adherence in comparison to more complex medication regimens. The study aimed to detect the extent of adherence to pharmacotherapy in Parkinson disease (PD) patients who take a minimum of three daily doses of drugs, and to identify factors associated with lower levels of adherence. Methods: The cohort was selected from non-demented PD patients. The 8-Item Morisky Medication Adherence Scale (MMAS-8), 8-Item Parkinson's Disease Questionnaire (PDQ-8), Geriatric Depression Scale (GDS), Non-Motor Symptom Assessment Scale (NMSS), 9-Item Wearing-off Questionnaire (WOQ-9), MDS-UPDRS III (motor examination), and IV (motor complications) scales were used in this study. Results: From a total of 124 subjects, 33.9% reported a high level of adherence, 29.8% reported a medium level of adherence, and 36.3% reported a low level of adherence to their pharmacotherapy. The level of non-adherence correlated with gender, longer disease duration, higher scores of PDQ-8, NMSS, WOQ-9, and MDS-UPDRS IV. Detailed analysis of NMSS demonstrated a correlation between the level of adherence and domains sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, and urinary symptoms. Independent risk factors for non-adherence were excessive daytime sleepiness, anhedonia, and forgetfulness. Conclusion: Non-adherence to more complicated medication regimens is frequent in PD patients and is associated with gender, longer PD duration, poorer quality of life, frequency and severity of non-motor symptoms, and more severe motor and non-motor fluctuations. Non-adherence was predicted by non-motor symptoms including fatigue, mood disturbances, and subjective cognitive complaints.

Clinical aspects of adherence to pharmacotherapy in Parkinson disease: A PRISMA-compliant systematic review.

BACKGROUND: Parkinson disease (PD) is the second most common neurodegenerative disease with various motor and nonmotor symptoms. Progressive course of PD requires frequent medication adjustments. Various combinations of drugs and dose regimens could be used to control symptoms. Thus, not surprisingly, adherence to pharmacotherapy is frequently suboptimal in these patients having negative effect on motor control and patient's quality of life. METHODS: In this article, we offer up-to-date review of adherence in PD compared with other chronic conditions. In addition, we summarize factors influencing level of adherence, ways of measuring, and methods of adherence optimization. For the review of adherence in PD, a literature search was undertaken using PubMed database and relevant search terms. Articles were screened for suitability and data relevance. RESULTS: PubMed and Scopus databases were systematically searched in 2016 and data extraction was a multistep process based on the PRISMA Guidelines. CONCLUSION: According to the recent data, sufficient control of motor symptoms and adequate quality of life are primary goals in the treatment of PD. Adherence to pharmacotherapy play a key role in this process, thus the medication should be tailored for each patient. In order to improve level of suboptimal adherence, these patients should have got recommended various dosing devices or alarms. Good communication with the patients and their relatives or caregivers is also essential.

Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients.

BACKGROUND: The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients. METHODS: We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items. RESULTS: A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue. CONCLUSIONS: This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.

Tacrolimus-induced parkinsonism in a patient after liver transplantation - case report.

BACKGROUND: Hepatic encephalopathy may manifest by a wide spectrum of neuropsychiatric symptoms, including cognitive impairment, seizures or extrapyramidal symptoms. The liver transplant can lead to improvement of the signs of encephalopathy but subsequent immunosuppressive treatment might possess pronounced neurotoxicity. CASE PRESENTATION: We present a case report of a patient with chronic liver disease who developed signs of Parkinsonism after an orthotopic liver transplant, with consecutive immunosuppressant treatment with tacrolimus. Despite the improvement of liver functions due to the cytostatic treatment, a progressive worsening of neuropsychiatric symptoms associated with the presence of tremor was observed. Metabolic as well as endocrine dysfunctions were excluded as the primary causes of this condition. A brain CT did not reveal structural pathology. Signs of severe, symmetric Parkinsonism - with resting tremor, bradykinesia, rigidity and severe postural instability were observed. A brain MRI was performed with the presence of T2- hyperintensities in basal ganglia bilaterally. Tacrolimus blood concentration was elevated; hence the dose was reduced and later switched to less toxic sirolimus. Subsequently, clinical signs markedly improved after treatment modification. Improvement of clinical symptomatology after tacrolimus discontinuation supports the drug-induced etiology of this neurological condition. CONCLUSIONS: Cytostatic treatment after solid organ transplantation often leads to signs of encephalopathy. If necessary, the dose of cytostatics needs to be reduced, or a less toxic agent must be chosen for the therapy. This modification is usually efficient with no further need for neurological intervention.

Neuropsychological Test Performance in Parkinsonism Without Dopaminergic Deficiency on [123I]-FP-CIT SPECT Imaging.

OBJECTIVES: To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson's disease (PD) without evidence of dopaminergic deficiency on [123]I-CIT single photon emission computed tomography imaging. METHODS: Data were obtained from the Parkinson's Progression Marker Initiative. The sample included 59 participants with scans without evidence of dopaminergic deficiency (SWEDD), 412 with PD, and 114 healthy controls (HC). Tests included Judgment of Line Orientation, Letter-Number Sequencing, Symbol Digit Modalities, Hopkins Verbal Learning Test-Revised, and Letter and Category Fluency. Multivariate analysis of variance was used to compare standardized scores between the groups. RESULTS: There was a statistically significant difference in performances between the groups, F(14,1155)=5.04; p<.001; partial η2=.058. Pairwise comparisons revealed significant differences in Category Fluency between SWEDD (M=0.22; SD=1.08) and HC (M=0.86; SD=1.15) and in Symbol Digit Modalities Test performance between SWEDD (M=45.09; SD=11.54) and HC (M=51.75; SD=9.79). No significant differences between SWEDD and PD were found. Using established criteria, approximately one in four participants in the SWEDD and PD groups met criteria for mild cognitive impairment (MCI). CONCLUSIONS: Individuals with SWEDD demonstrate significantly worse mental processing speed and semantic fluency than HC. The neuropsychological test performances and rates of MCI were similar between the SWEDD group and PD groups, which may reflect a common pathology outside of the nigrostriatal pathway. (JINS, 2018, 24, 646-651).

Differences in MDS-UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration.

BACKGROUND: The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS-UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD. METHODS: For this cross-sectional study, demographic data and MDS-UPDRS scores were collected, including HY stage. Subscores on MDS-UPDRS Parts I through IV were analyzed using 1-way analyses of variance for each HY stage and in 5-year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states. RESULTS: The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0-5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS-UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5-year increments of disease duration, MDS-UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states. CONCLUSIONS: MDS-UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5-year increments of disease duration in the first 15 years of the disease.

Cognition in Patients With a Clinical Diagnosis of Parkinson Disease and Scans Without Evidence of Dopaminergic Deficit (SWEDD): 2-Year Follow-Up.

OBJECTIVE AND BACKGROUND: More than 10% of patients clinically diagnosed with Parkinson disease demonstrate normal dopamine uptake on dopamine transporter single-photon emission computed tomography (DaTscan), but little is known about how cognitive function differs between patients with dopamine deficiency on DaTscan and patients with scans without evidence of dopaminergic deficit (SWEDD). We compared the cognitive function of these two groups of patients over 2 years. METHODS: We retrospectively analyzed data obtained from the Parkinson's Progression Markers Initiative on 309 participants clinically diagnosed with idiopathic Parkinson disease who had scored in the normal range on the Montreal Cognitive Assessment at baseline and had completed 1- and 2-year follow-up visits. We compared the Montreal Cognitive Assessment scores at 1 and 2 years between the 42 participants with SWEDD and the 267 with dopamine deficiency. RESULTS: Mean cognitive scores did not differ significantly between groups at 1 year, but at 2 years the participants with SWEDD performed more poorly. At 2 years, 31% of the participants with SWEDD versus 15% of those with dopamine deficiency had statistically reliable cognitive impairment. CONCLUSIONS: This study provides evidence that some individuals clinically diagnosed with idiopathic Parkinson disease but with SWEDD demonstrate early cognitive decline. The results also suggest that recently diagnosed patients with SWEDD may be at even greater risk for cognitive decline than patients with DaTscan-confirmed early-stage Parkinson disease. While patients with SWEDD likely represent a heterogeneous group of etiologies, our results highlight the need to monitor these patients' cognitive function over time.