Effects of transcutaneous spinal direct current stimulation in idiopathic restless legs patients.

BACKGROUND: Transcutaneous spinal direct current stimulation (tsDCS) is a new non-invasive technique to modulate spinal cord activity. The pathophysiological concept of primary RLS proposes increased spinal excitability. OBJECTIVE: This pilot study used tsDCS to reduce pathologically enhanced spinal excitability in RLS patients and to thereby ameliorate clinical symptoms. METHODS: 20 patients with idiopathic RLS and 14 healthy subjects participated in this double-blinded, placebo-controlled study. All participants received one session of cathodal, anodal and sham stimulation of the thoracic spinal cord for 15 min (2.5 mA) each, in randomized order during their symptomatic phase in the evening. The soleus Hoffmann-reflex with Hmax/Mmax-ratio and seven different H2/H1-ratios (of two H-reflex responses to double stimuli) were measured. The RLS symptoms were assessed by a visual analogue scale (VAS). All parameters were measured before and twice after tsDCS. RESULTS: RLS patients showed increased H2/H1-ratios during their symptomatic phase in the evening. Application of anodal stimulation led to a decreased H2/H1-ratio for 0.2 and 0.3 s interstimulus intervals in patients. Furthermore, application of anodal and cathodal stimulation led to a reduction in restless legs symptoms on the VAS, whereas application of sham stimulation had no effects on either the VAS or on the H2/H1-ratio in patients. VAS changes did not correlate with changes of H2/H1-ratios. CONCLUSIONS: This is the first tsDCS study in idiopathic RLS, which resulted in short-lasting clinical improvement. Furthermore, our results support the pathophysiological concept of spinal cord hyperexcitability in primary RLS and provide the basis for a new non-pharmacological treatment tool.

Differentiation of typical and atypical Parkinson syndromes by quantitative MR imaging.

BACKGROUND AND PURPOSE: The differential diagnosis of Parkinson syndromes remains a major challenge. Quantitative MR imaging can aid in this classification, but it is unclear which of the proposed techniques is best suited for this task. We, therefore, conducted a head-to-head study with different quantitative MR imaging measurements in patients with IPS, MSA-type Parkinson, PSP, and healthy elderly controls. MATERIALS AND METHODS: Thirty-one patients and 13 controls underwent a comprehensive quantitative MR imaging protocol including R2*-, R2- and R1-mapping, magnetization transfer, and DTI with manual region-of-interest measurements in basal ganglia regions. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction and an ROC. RESULTS: The best separation of MSA from IPS in patients and controls could be achieved with R2*-mapping in the PU, with an ROC AUC of ≤0.96, resulting in a sensitivity of 77.8% (with a specificity 100%). MD was increased in patients with PSP compared with controls and to a lesser extent compared with those with IPS and MSA in the SN. CONCLUSIONS: Among the applied quantitative MR imaging methods, R2*-mapping seems to have the best predictive power to separate patients with MSA from those with IPS, and DTI for identifying PSP.

Diurnal time course of heat pain perception in healthy humans.

Rapid skin heating by infrared lasers can be used to investigate the integrity of the nociceptive system by activating A-delta and C fibers. The aim of our study was to analyze if healthy humans exhibit any clinically relevant diurnal variations in their heat pain sensitivity. Circadian A-delta fiber function was analyzed by studying N2 and P2 components of laser-evoked potentials (LEP) and pain thresholds evoked by laser stimulation of the foot every 2h from 8a.m. to 10p.m. in 15 healthy subjects. Heat stimuli were generated by an infrared Tm-YAG laser and were delivered to an area of 4 cm × 4.5 cm on the dorsum of the right or left foot in 3 runs of incremental and decremental intensities. After each stimulus subjects were asked to classify the intensity of pain with a numeric rating scale (NRS). LEPs were recorded with fixed stimulus intensities that were 1.5× of the pain threshold. Data were collected with the SynAmps System (Neuroscan, El Paso, USA) and averaged across 35-40 trials. Laser-induced heat pain thresholds and circadian latencies of LEP did not significantly vary during the day. Our results correspond with previous studies that did not detect any consistent significant diurnal variations in perception of heat pain perception using contact thermodes. The intensity of pain perception did not demonstrate any correlation with mood or sleep parameters as measured with the Beck Depression Inventory (BDI), the subjective sleep scales Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS).

Classifying risk factors for dyskinesia in Parkinson's disease.

BACKGROUND: Currently there is no classification of risk factors applicable to an individual patient with Parkinson's disease for the development of dyskinesia. METHODS: We conducted literature search to identify and classifying risk factors into groups - (a) intrinsic vs extrinsic and (b) modifiable vs non-modifiable. RESULTS: Younger age, young age of onset and severity of PD are major intrinsic non-modifiable risk factors for dyskinesia, female gender is another factor but not independent of other factors. Genetic expression and plasticity may determine pre-disposition to age of onset of PD and dyskinesia, these are currently non-modifiable factors arising due to an interaction of intrinsic and extrinsic factors. Lower initial body weight and weight loss during the course of the disease increase the risk of dyskinesia. Levodopa dose per kilogram body weight is a more significant risk factor than absolute levodopa dose. Early use of longer acting non-levodopa (i.e. dopamine agonists) medications delays the onset of dyskinesia. Interaction between body weight, levodopa dose and mode and duration of drug delivery is a significant modifiable factor. CONCLUSION: Dyskinesia in PD arises as a consequence of the interaction of intrinsic versus extrinsic and modifiable versus non-modifiable factors. Identification and manipulation of modifiable factors for an individual patient may reduce the risk and burden of dyskinesia. Adjustment of levodopa dose according to body weight during the course of the disease seems to be a significant modifiable risk factor for dyskinesia.

Influence of intrinsic noise generated by a thermotesting device on thermal sensory detection and thermal pain detection thresholds.

Various factors can influence thermal perception threshold measurements and contribute significantly to unwanted variability of the tests. To minimize this variability, testing should be performed under strictly controlled conditions. Identifying the factors that increase the variability and eliminating their influence should increase reliability and reproducibility. Currently available thermotesting devices use a water-cooling system that generates a continuous noise of approximately 60 dB. In order to analyze whether this noise could influence the thermal threshold measurements we compared the thresholds obtained with a silent thermotesting device to those obtained with a commercially available device. The subjects were tested with one randomly chosen device on 1 day and with the other device 7 days later. At each session, heat, heat pain, cold, and cold pain thresholds were determined with three measurements. Bland-Altman analysis was used to assess agreement in measurements obtained with different devices and it was shown that the intersubject variability of the thresholds obtained with the two devices was comparable for all four thresholds tested. In contrast, the intrasubject variability of the thresholds for heat, heat pain, and cold pain detection was significantly lower with the silent device. Our results show that thermal sensory thresholds measured with the two devices are comparable. However, our data suggest that, for studies with repeated measurements on the same subjects, a silent thermotesting device may allow detection of smaller differences in the treatment effects and/or may permit the use of a smaller number of tested subjects. Muscle Nerve 40: 257-263, 2009.

Dopaminergic treatment is associated with decreased body weight in patients with Parkinson's disease and dyskinesias.

BACKGROUND AND PURPOSE: Several studies suggested that patients with advanced Parkinson's disease (PD) showed a too low body weight when compared with age-matched, healthy subjects. We aimed to investigate whether PD patients with dyskinesias display body weight alterations and to observe any correlations between medication and other putative determinants. METHODS: Charts of 166 PD patients with fluctuations and dyskinesias, admitted within 6 months to a German movement disorders clinic, were investigated for body mass index (BMI), age at onset, disease duration, Unified Parkinson's Disease Rating Scale motor score, eating coordination and medication. RESULTS: Analysis showed that 4.2% of PD patients were underweight (BMI < 18.5 kg/m(2)), 46.4% were normal (BMI > 18.5-25 kg/m(2)), 33.7% were overweight (BMI > 25-30 kg/m(2)), 15.7% were obese (BMI > 30 kg/m(2)). Daily levodopa dosage per kg and total dopaminergic dosage per kg body weight were negatively correlated with BMI. Overall, patients' BMI had not significantly changed within 2 years of follow-up. CONCLUSIONS: In sum, advanced PD patients showed a reduced BMI when compared with a control population obtained from an age-matched group taken from a survey of the German Federal Office for Statistics. Our findings indicate that patients with a lower BMI received a higher cumulative levodopa dosage and that levodopa may be responsible for weight loss in PD.

Pregabalin in restless legs syndrome with and without neuropathic pain.

BACKGROUND: Restless legs syndrome (RLS) is a common neurological disorder complicated in many patients by augmentation to dopaminergic therapy or comorbidities such as neuropathic pain. AIMS: To explore the effectiveness of pregabalin in RLS in a pragmatic clinical setting. METHODS: After observing improvement of restless legs symptoms in seven patients treated with pregabalin for neuropathic pain, we extended the clinical observation to a total of 16 patients with secondary RLS, in most of them due to neuropathy, and to three patients with idiopathic RLS. RESULTS: Three patients discontinued pregabalin because of side effects (rash, fatigue, loss of efficacy). The other 16 patients self-rated a satisfactory or good alleviation of RLS symptoms and maintained pregabalin, five with add-on medication, on a mean daily dose of 305 mg (standard deviation, 185 mg), and with a mean duration of 217 (standard deviation, 183) days. CONCLUSION: These data propose pregabalin as a new option in the treatment of secondary RLS for patients with neuropathic pain, which should be further investigated with randomized, placebo-controlled trials.

[Restless legs syndrome: therapeutic possibilities in the medical practice]. / Restless-Legs-Syndrom--idiopathisch oder sekundär? Bei ruhelosen Beinen erst mal die Ursache klären.

The diagnosis of restless legs syndrome is made on the basis of the clinical symptoms and, if applicable, complemented with a polysomnography. This is followed by neurophysiological examinations and laboratory diagnostics and permits a differentiation between idiopathic and secondary RLS. The therapy depends upon the form and severity of the disease. For secondary RLS, the primary disease must be treated or the symptom-inducing medication must be discontinued. An idiopathic RLS is treated with drugs. Primarily, L-dopa/benserazide and dopaminergic agonists are used, but opioids and anticonvulsants are also successful.