Ján Benetin

Impulse control disorders associated with dopaminergic medication in patients with pituitary adenomas.

Objective:Impulse control disorders (ICDs) such as pathological gambling, compulsive shopping, compulsive eating, and hypersexuality are a matter of growing interest, especially in patients with Parkinson disease who are on dopamine replacement therapy. It was recently reported that ICDs are associated with other disorders also treated with dopaminergic drugs (dopamine agonists) such as restless legs syndrome, multiple system atrophy, progressive supranuclear palsy, and fibromyalgia. The aim of this study was to determine the prevalence of ICDs in patients with pituitary adenomas who take dopamine agonists (DAs). Methods:Twenty consecutive patients with pituitary adenomas (mostly prolactinomas) taking DAs were assessed. All participated in a structured interview focused on ICDs, which was conducted by a physician. Results:Two (10%) of 20 subjects had a condition diagnosed as ICD. The first patient is a 35-year-old man with giant macroprolactinoma who was alternately treated with different types of DAs (cabergoline, bromocriptine, and quinagolide). He developed compulsive eating and pathological gambling. The second patient is a 53-year-old man with macroprolactinoma who suffered from severe hypersexuality after cabergoline was begun. Conclusions:This study demonstrates the importance of systematic screening for ICDs in patients taking dopaminergic medication regardless of their primary condition.

8-OHdG in Cerebrospinal Fluid as a Marker of Oxidative Stress in Various Neurodegenerative Diseases

Background: The 8-hydroxy-2 deoxyguanosine (8-OHdG) is a product of nucleoside oxidation of DNA and a reliable marker of oxidative stress markers. Increased levels of oxidative stress have been reported in the cerebrospinal fluid (CSF) of patients with various neurodegenerative disorders. Objective: In search of a biochemical indicator of Parkinson’s disease (PD), we analyzed the levels 8-OHdG in the CSF of 99 patients, using ELISA to assess the differences between various neurodegenerative disorders. Results: Statistically significant higher CSF levels (p = 0.022) of 8-OHdG in non-demented PD patients as compared to the control group were observed. No differences between CSF 8-OHdG levels and age at the time of lumbar puncture, presence or severity of dementia, or gender were found. Conclusions: 8-OHdG levels could be potentially useful in the neurochemically supported diagnosis of PD.

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.

Postural reactions to neck vibration in Parkinson's disease.

To test the hypothesis that reduced reactions to proprioceptive input signals contribute to postural instability in Parkinsons disease (PD), pulses of mechanical vibration were applied to the neck muscles of PD patients and healthy controls. This stimulus elicits postural reactions in standing subjects. Participating were 13 moderately affected PD patients, 13 severely affected PD patients, and 13 age‐matched healthy subjects. Patients were tested on and off medication. Three‐second‐long pulses of vibration were regularly (10 times) applied to the posterior neck muscles while subjects kept their eyes open or closed. Postural responses to the stimuli were measured by static posturography. No intergroup difference in the pattern and latencies of responses was found. However, the amplitudes of the postural reactions (shift of center of foot pressure) were significantly larger in advanced PD patients; those of moderately affected PD patients did not differ from those of control subjects. Moreover, the size of postural responses in both latter groups decreased across the trial contrary to that of advanced PD patients. Comparison of the measures during on and off testing revealed no significant differences. These results indicate that neither afferent proprioceptive deficits nor central integrative functions but rather scaling and habituation of erroneous proprioceptive information are disturbed in the postural control of advanced PD. Nondopaminergic structures seem to be responsible for this impairment.

Static posturography and infraclinical postural instability in early-stage Parkinson's disease.

We read with interest the recent article by Chastan et al. on the discordance between postural instability measured by posturography and the absence of clinical symptoms in patients with early-stage Parkinson’s disease (PD). They compared nine very mildly affected PD patients (mean Hoehn and Yahr (H&Y) stage was 1.22 and the mean motor score of the Unified PD Rating Scale (UPDRS) was 10.3) and 18 age-matched control subjects. The PD patients swayed significantly over a greater area and with higher mediolateral energy during static balance conditions, both with open (OE) and with closed eyes (CE). Stance on a mobile platform (dynamic condition) revealed only slight differences: PD subjects had a greater sway area in the anteriorposterior direction when their eyes were closed. These results were interpreted to be a sign of infraclinical postural instability in early-stage PD. In order to verify this surprising finding of infraclinical postural instability, we tested static balance of early-stage PD patients and healthy controls. Eighteen consecutive PD patients without a history of falling or other balance problems were included. Their average age was 63.4 6 7.2 years, duration of PD was 2.8 6 1.4 years, H&Y score was 1.7 6 0.5, and the UPDRS motor score was 14.4 6 5.8. The control group consisted of 17 ageand sex-matched healthy subjects (average age was 64.1 6 6.0). All subjects underwent static balance measurements using a posturographic platform (Kistler, type 9281B). Their sway activity was recorded in a 30-second-long trial, once with OE and once with CE. They were instructed to remain in upright stance (feet next to each other, splayed at an angle of 308, arms hanging by the sides) and to refrain from any voluntary movements during the recording. Signals from the platform were amplified and digitized at a sampling rate of 40 Hz. The root mean square, sway path, and velocity values for mediolateral (X) and anterior-posterior (Y) displacements of the center of foot pressure were calculated and statistically evaluated on the basis of the raw data. Table 1 gives the mean 6 standard deviation of the tested variables. The results of statistical analysis by Student’s t-test are given as ‘‘P value.’’ Unlike Chastan et al., we did not find any significant difference in any of the tested variables between early-stage PD patients (even more clinically affected than Chastan’s patients) and healthy age-matched controls. Our study demonstrates that the issue of the clinical utility of static posturography for diagnosing early balance problems in PD is still open.

Nonmotor Symptoms in Early- and Advanced-Stage Parkinson's Disease Patients on Dopaminergic Therapy: How Do They Correlate with Quality of Life?

To determine the impact of nonmotor symptoms (NMS) on health-related quality of life (HRQoL) we examined 100 Parkinsons disease (PD) patients on dopaminergic medications. An “early-stage” (ES) and an “advanced-stage” (AS) groups were formed. HRQoL was established by the questionnaire PDQ-8, number of NMS by NMSQuest, and severity and frequency of NMS by the assessment scale NMSS. The total NMS averaged 11.3 (ES = 9.6, AS = 12.8). The NMSS domain correlation profiles for ES and AS did not fundamentally differ; however, the domains attention/memory and mood/apathy correlated moderately to strongly with HRQoL in ES, while the sleep/fatigue domain correlated moderately with HRQoL in AS. Weakly correlating domains were sleep/fatigue in ES and cardiovascular, attention/memory, and mood/apathy domains in AS. In view of these findings we strongly recommend systematic, active screening and therapy for neuropsychiatric disorders (mood, cognitive and sleep disorders, and fatigue) at the initial diagnosis and throughout the entire course of PD.

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.