Michal Minár

Pain in Parkinson´s Disease: A Cross-Sectional Study of Its Prevalence, Types, and Relationship to Depression and Quality of Life

Pain is an important and distressing symptom in Parkinson’s disease (PD). Our aim was to determine the prevalence of pain, its various types and characteristics, as well as its impact on depression and quality of life (QoL) in patients with PD. How pain differs in early- and advanced-stage PD and male and female PD patients was of special interest. One hundred PD patients on dopaminergic medications had a neurological examination and participated in a structured interview on pain characteristics and completed standardized questionnaires. A total of 76% of the patients had pain. The following types of pain were present: musculoskeletal pain accounted for 41% of the total pain, dystonic pain for 17%, central neuropathic pain for 22%, radicular pain for 27%, and other pains (non-radicular low back pain, arthritic, and visceral pain) made up 24%. One type of pain affected 29% of all the subjects, two types 35%, three types 10%, and four types of pain were reported by 2%. All types of pain were more prevalent in advanced-stage PD subjects than in early-stage PD subjects, except for arthritic pain (subclassified under”other pain”). The frequency and intensity of actual, average, and worst experienced pain were significantly more severe in advanced-stage subjects. PD subjects with general pain and in advanced stages were more depressed and had poorer QoL. Depression correlated with worst pain in the last 24 hours and with pain periodicity (the worst depression score in patients with constant pain). QoL correlated with average pain in the last 7 days. Pain is a frequent problem in PD patients, and it worsens during the course of the disease.

Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease

The Movement Disorder Society-Unified Parkinsons Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinsons disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, I and IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS.

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

The Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinsons 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.

Restless legs syndrome in pregnancy is connected with iron deficiency

OBJECTIVE Almost one-third of pregnant women develop symptoms of restless legs syndrome (RLS), which could have a negative impact on quality of life and the course of pregnancy and/or labor. The aim of our study was to determine possible risk factors for developing RLS in pregnant women. METHODS A total of 300 random women in the third trimester of gravidity filled out a simple questionnaire based on the official diagnostic criteria for RLS. Respondents positive for RLS were interviewed to further characterize their symptoms. The parameters of iron metabolism were examined based on blood samples. All data were statistically analyzed. RESULTS We detected significantly lower hemoglobin levels with signs of hypochromic anemia typical of iron deficiency in RLS-positive respondents, although oral iron supplementation was significantly higher in this group. The overall severity of symptoms correlated inversely with hemoglobin level. CONCLUSION According to our results, it appears that serum iron level disturbances play a crucial role in the pathophysiology of secondary RLS in pregnant women.

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.

Validation of the Official Slovak Version of the Unified Dyskinesia Rating Scale (UDysRS).

After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinsons disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be ≥0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was ≥0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society.

Prevalence and impact of restless legs syndrome in university students

Restless legs syndrome (RLS) is one of the most common neurological disorders. It is characterized by an irresistible urge to move one’s legs, the major sensory symptom, and can have an overwhelming impact on quality of life. Apparently changes in central nervous system iron metabolism lead to dopamine dysfunction, which is thought to be responsible for unpleasant feelings and movements of mainly the legs in the evening or during the night. Many epidemiological studies of RLS in the past used different criteria. The consensus on standardized diagnostic criteria of the International RLS Study Group (IRLS-SG) led to agreement on a definition. These criteria were also used in the REST (RLS Epidemiology, Symptoms, and Treatment) project involving a cohort of several thousand subjects. The prevalence of RLS in the general adult population was 7.2% for individuals with symptoms of any frequency and 2.7% for those with RLS at least twice a week and at least moderate distress (so-called RLS sufferers). The occurrence of RLS increases with age in adults, but it is not rare in children. It was reported that 1.9% of 8to 11-year-olds and 2.0% of 12to 17-year-olds met IRLS-SG criteria (0.5% and 1.0% were RLS sufferers, respectively). However, data on the prevalence of RLS in the specific population of young adults have not been available so far. Three hundred consecutively enrolled students of the Faculty of Medicine, Comenius University Bratislava, participated in our study. They answered 4 specific questions, that is, essential criteria for RLS according to the IRLSSG, in a brief questionnaire that also collected demographic data. If all 4 questions were answered positively, the respondent was considered RLS positive; otherwise, the respondent was considered RLS negative. RLS-positives subsequently completed a second part of the questionnaire that a physician or trained nurse applied. The aim of this part was to confirm the diagnosis of RLS and describe its particular features, a methodology already validated and successfully used in our previous study. All subjects gave their written informed -----------------------------------------------------------*Correspondence to: Peter Valkovič, MD, PhD, Second Department of Neurology, Faculty of Medicine, Comenius University, Limbov a 5, 83305 Bratislava, Slovakia; Peter.Valkovic@gmail.com

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

BackgroundHepatic 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 presentationWe 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.ConclusionsCytostatic 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.

Effects of rasagiline on freezing of gait in Parkinson's disease - an open-label, multicenter study.

AIMS Freezing of gait is a disabling symptom in advanced Parkinsons disease. Positive effects have been suggested with MAO-B inhibitors. We report on an open label clinical study on the efficacy of rasagiline as add-on therapy on freezing of gait and quality of life in patients with Parkinsons disease. METHODS Forty two patients with freezing of gait were treated with 1 mg rasagiline daily as an add-on therapy. Patients were assessed at baseline and after 1, 2 and 3 months of treatment. Freezing of gait severity was assessed using the Freezing of Gait Questionnaire, motor impairment by the modified MDS UPDRS part III, and quality of life using the PDQ-39 questionnaire. RESULTS Patients treated with rasagiline had a statistically significant decrease in FoG-Q score and modified MDS UPDRS score after 1, 2 and 3 months of therapy. A moderately strong (r = 0.686, P = 0.002) correlation between the effects on mobility and freezing of gait was found. We also observed a statistically significant improvement in global QoL and in the subscales mobility, ADL, stigma and bodily discomfort in patients after 3 months of rasagiline therapy. A significant correlation (r = 0.570, P = 0.02) between baseline FoG-Q score and the baseline score for the PDQ Mobility subscale was found. CONCLUSION In our study rasagiline as add-on antiparkinsonian therapy significantly improved mobility, freezing of gait and quality of life. The positive effect on freezing of gait appears to be related to improvement of mobility.

Thyroid-induced worsening of parkinsonian tremor resistant to drugs and subthalamic nucleus deep brain stimulation.

Introduction. Symptoms of both hypothyroidism and thyrotoxicosis can be easily overlooked in patients with Parkinsons disease (PD). We report on a patient whose parkinsonian tremor worsened and proved refractory not only to common treatment, but also to deep brain stimulation (DBS). Case Presentation. A 61-year-old woman with advanced PD underwent bilateral subthalamic DBS, with an excellent outcome. Twenty-one months after the surgery, however, patients resting/postural tremor markedly worsened. There was a slight improvement for 1 month after repeated adjustments of DBS parameters, but then the tremor worsened again. Since even a minimal increase of the dose of dopaminergic drugs caused extremely severe dyskinesias, an anticholinergic drug biperiden and benzodiazepine clonazepam were introduced, what helped for another month. With the onset of severe diarrhoea, a laboratory workup was performed. Thyrotoxicosis was detected. During treatment with the antithyroid agent carbimazole, the parkinsonian tremor clearly improved within two weeks. Conclusion. A hyperthyroid state can markedly exaggerate all forms of tremor, as well as other types of movement disorders. This condition can be overlooked or masked by other symptoms. Therefore, if the tremor in a patient with PD gradually worsens and proves resistant to the usual treatment, examine the thyroid gland.