Peter Valkovič

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.

Objective measurement of muscle rigidity in parkinsonian patients treated with subthalamic stimulation

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be an effective treatment for Parkinsons disease (PD). The intraoperative positioning of DBS electrodes and postoperative adjustment of the stimulation parameters, however, require continuous, precise evaluation. Moreover, ambulatory measurements of the symptoms would also help to evaluate changes in the progression of PD in these patients. To this aim, we objectified rigidity measurements via surface EMG recordings of the Mm. biceps (bic) and triceps brachii (tric) in patients treated with chronic stimulation of the STN. We show that cessation and initiation of DBS have effects on the EMG profile during standardized extension and flexion movements in the elbow joint. These data correlate significantly with clinical ratings. Thus, EMG recordings of the Mm. bic and tric during this standardized extension‐flexion movement can be used to objectively measure rigidity and to monitor its course over time. In view of its low technical requirements, this technique lends itself to use during DBS implantation surgery and in the clinical environment.

Postural reactions to soleus muscle vibration in Parkinson's disease: Scaling deteriorates as disease progresses

Previous research has shown that Parkinsons disease (PD) patients, especially those with postural instability, respond hyperactively to visual, vestibular, and neck proprioceptive sensory manipulation. To determine if this impairment of the sensory information scaling holds true for the lower leg proprioceptive system, we studied postural responses to mechanical vibration (which affects the muscle spindle Ia afferents) applied to the soleus muscles of PD subjects and healthy controls. Early-stage and advanced-stage PD patients as well as age-matched control subjects participated. Each group comprised 11 subjects. Nine pulses of 3-s long vibration were applied randomly to both soleus muscles while subjects kept their eyes closed. Postural responses to these stimuli were measured by static posturography. The effect of dopaminergic medication was established by testing patients in both ON and OFF treatment phases. There was no intergroup difference in the pattern or latencies of responses. However, the amplitudes were significantly larger in advanced PD patients; controls did not differ from early-stage PD patients. Dopaminergic medication had no significant effect on any of the measures. The scaling of postural reactions triggered by lower leg proprioception is disturbed in advanced PD. Neither afferent proprioceptive deficits nor inaccurate timing is involved. This study gives further evidence for the generalized impairment of the scaling of postural responses evoked whenever there is a sudden change of sensory conditions, as occurs with the progression of PD. Such impairment could play a significant role in the pathophysiology of postural instability and falls in PD patients.

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.

Markers of oxidative stress in plasma and saliva in patients with multiple sclerosis

BACKROUND Oxidative stress plays a role in multiple sclerosis. Saliva can be potentially used to study the disease progression or treatment, because of its non-invasiveness and easy collection. But studies on saliva and multiple sclerosis are missing. The aim of this study was to compare the concentrations of salivary oxidative stress markers in patients and healthy controls. OBJECTIVE Whole saliva and blood samples were collected from 29 patients and 29 healthy controls. Samples were collected during relapse, after corticosteroid therapy, and after three months. Markers of oxidative, carbonyl stress and antioxidant status were measured. RESULTS In plasma, thiobarbituric acid reacting substances, advanced oxidation protein products and fructosamine were significantly higher in patients compared to controls (by 271%, 46% and 24%, respectively; p<0.01). Total antioxidant capacity in plasma was lower by 20% (p<0.01) in patients versus controls. In saliva, higher levels of thiobarbituric acid reacting substances and advanced glycation end-products were observed in patients when compared to controls (by 51% and 49% respectively; p<0.01). Ferric reducing ability was reduced by 38% (p<0.05) in patients with multiple sclerosis. CONCLUSION According to our knowledge, this is the first report showing higher markers of oxidative stress and lower antioxidant status in patients with multiple sclerosis in saliva.

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.

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.

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.

Parkinsonian patients show impaired predictive smooth pursuit

To determine if patients with Parkinson’s disease (PD) are able to use a visual contextual cue to induce a predictive change in smooth pursuit direction and if this ability depends on the state of the dopaminergic system, we measured predictive smooth pursuit in nine patients with mild to moderate PD during OFF and ON medication. These values were compared with those of nine agematched and sex-matched healthy controls.Our focus was on the horizontal smooth pursuit when subjects pursued a downward moving target entering a ± 90 deg curve. The target moved on a homogeneous background or on a static “street” that indicated the future trajectory of the target. Our main result is that PD patients were impaired in eliciting predictive smooth pursuit using the context information of the street compared to healthy subjects. The control group elicited predictive pursuit 250 ms before target onset. In contrast, PD patients showed significantly longer latency (100–120 ms) and reduced maximal pursuit velocity. However, without the street guiding pursuit, a delay of about 250 ms was seen in both groups. There was no significant difference in the smooth pursuit performance between OFF and ON medication in the patient group.These results show that earlystage PD patients are impaired in the use of static visual information as a cue for predictive pursuit compared to controls and that this deficit does not depend on dopaminergic medication. In the context of predictive eye movement, the involvement of the striatal-frontal pathway and the spatial working memory is discussed.