Investigation of oxidative stress in patients with multifocal motor neuropathy.

Background and purpose: Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. Methods: We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. Results: MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Conclusion: Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

[Diseases with peripheral motor symptoms]. / Perifériás motoros tünettannal társuló kórképek.

Diseases with peripheral motor symptoms are a rare, but important subgroup of the all peripheral neuropathies, radiculopathies and neuronopathies. In these mostly progressive neuropathies, the clinical features include pure motor symptoms with weakness and wasting of the striated muscles. The differentiation of these diseases is frequently a challenge for qualified clinical neurologists. A careful history taking, the disease time course, the findings of routine clinical physical examination and the electrophysiological studies are all necessary in the diagnostic procedure. The aim of this publication is to overview the clinical characteristics of the pure motor peripheral neuropathies, to consider the diagnostic steps and the differential diagnosis, and finally to summarize the treatment options.

Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions.

Background/Aim Migraine is a risk factor for the formation of silent brain white matter lesions (WMLs) that are possibly ischemic in nature. Although dysfunction of the L-arginine/nitric oxide (NO) pathway has been associated with oxidative stress and endothelial dysfunction in migraine, its role in WML development has not been specifically investigated. Thus, this prospective study aimed to measure the serum concentrations of the NO substrate L-arginine, the NO synthase inhibitor asymmetric dimethylarginine (ADMA), and the L-arginine transport regulator symmetric dimethylarginine (SDMA) in migraine patients in a headache-free period. Methods All participants underwent MR imaging to assess for the presence of WMLs on fluid-attenuated inversion recovery imaging. Altogether 109 migraine patients (43 with lesions, 66 without lesions) and 46 control individuals were studied. High-performance liquid chromatography was used to quantify L-arginine, ADMA and SDMA serum concentrations. Migraine characteristics were investigated, and participants were screened for risk factors that can lead to elevated serum ADMA levels independent of migraine. Results Migraine patients and controls did not differ in regard to vascular risk factors. Migraineurs with WMLs had a longer disease duration ( p < 0.001) and a higher number of lifetime headache attacks ( p = 0.005) than lesion-free patients. Higher L-arginine serum levels were found in both migraine subgroups compared to controls ( p < 0.001). Migraine patients with WMLs showed higher ADMA concentrations than lesion-free patients and controls ( p < 0.001, for both). In migraineurs, the presence of WMLs, aura and increasing age proved to be significant predictors of increased ADMA levels ( p = 0.008, 0.047 and 0.012, respectively). SDMA serum levels of lesional migraineurs were higher than in nonlesional patients ( p < 0.001). The presence of lesions and increasing age indicated an increased SDMA level ( p = 0.017 and 0.001, respectively). Binary logistic regression analysis showed that ADMA level ( p = 0.006), increasing age ( p = 0.017) and the total number of lifetime migraine attacks ( p = 0.026) were associated with an increased likelihood of exhibiting WMLs. There was no significant effect of age on ADMA and SDMA concentrations in controls. Conclusions Elevated ADMA levels may impact the pathogenesis of migraine-related WMLs by influencing cerebrovascular autoregulation and vasomotor reactivity. Higher SDMA concentrations may indirectly influence NO synthesis by reducing substrate availability. Elevated L-arginine serum levels might reflect an increased demand for NO synthesis.

How Efficient Is Subthalamic Deep Brain Stimulation in Reducing Dyskinesia in Parkinson's Disease?

BACKGROUND: Dyskinesia is among the most troublesome symptoms of advanced Parkinson's disease (PD). The recently developed Unified Dyskinesia Rating Scale (UDysRS) can simultaneously measure several subjective and objective aspects of dyskinesia, irrespective of the other motor symptoms of PD. Despite the advantages of deep brain stimulation (DBS), previous studies on DBS have not used the UDysRS yet. METHODS: In this prospective study, 71 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. The severity of PD-related symptoms was assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS). The presence and severity of dyskinesia were specifically measured by the UDysRS and patient diaries. RESULTS: At baseline, all 71 patients had dyskinesia, but 1 year after DBS implantation, 25 patients were dyskinesia-free, and an additional 19 had only mild dyskinesia. The total score on the UDysRS decreased from 38.0 ± 17.8 to 10.8 ± 13.0 (p < 0.001). Besides this, all parts of the UDysRS showed significant improvement after STN DBS treatment, and the magnitude of these changes had a large effect size. The total score of MDS-UPDRS improved from 76.5 ± 24.3 to 60.4 ± 21.4 points (p < 0.001). CONCLUSIONS: Based on our results, UDysRS can reliably detect improvements in dyskinesia after DBS implantation.

Changes of migraine-related white matter hyperintensities after 3 years: a longitudinal MRI study.

OBJECTIVE/BACKGROUND: The aim of this longitudinal study was to investigate changes of migraine-related brain white matter hyperintensities 3 years after an initial study. Baseline quantitative magnetic resonance imaging (MRI) studies of migraine patients with hemispheric white matter hyperintensities performed in 2009 demonstrated signs of tissue damage within the hyperintensities. The hyperintensities appeared most frequently in the deep white matter of the frontal lobe with a similar average hyperintensity size in all hemispheric lobes. Since in this patient group the repeated migraine attacks were the only known risk factors for the development of white matter hyperintensities, the remeasurements of migraineurs after a 3-year long follow-up may show changes in the status of these structural abnormalities as the effects of the repeated headaches. METHODS: The same patient group was reinvestigated in 2012 using the same MRI scanner and acquisition protocol. MR measurements were performed on a 3.0-Tesla clinical MRI scanner. Beyond the routine T1-, T2-weighted, and fluid-attenuated inversion recovery imaging, diffusion and perfusion-weighted imaging, proton magnetic resonance spectroscopy, and T1 and T2 relaxation time measurements were also performed. Findings of the baseline and follow-up studies were compared with each other. RESULTS: The follow-up proton magnetic resonance spectroscopy studies of white matter hyperintensities showed significantly decreased N-acetyl-aspartate (median values 8.133 vs 7.153 mmol/L, P=.009) and creatine/phosphocreatine (median values 4.970 vs 4.641 mmol/L, P=.015) concentrations compared to the baseline, indicating a more severe axonal loss and glial hypocellularity with decreased intracellular energy production. The diffusion values, the T1 and T2 relaxation times, and the cerebral blood flow and volume measurements presented only mild changes between the studies. The number (median values 21 vs 25, P<.001) and volume (median values 0.896 vs 1.140 mL, P<.001) of hyperintensities were significantly higher in the follow-up study. No changes were found in the hemispheric and lobar distribution of hyperintensities. An increase in the hyperintensity size of preexisting lesions was much more common than a decrease (median values 14 vs 5, P=.004). A higher number of newly developed hyperintensities were detected than disappeared ones (130 vs 22), and most of them were small (<.034 mL). Small white matter hyperintensities in patients with a low migraine attack frequency had a higher chance to disappear than large white matter hyperintensities or white matter hyperintensities in patients with a high attack frequency (coefficient: -0.517, P=.034). CONCLUSIONS: This longitudinal MRI study found clinically silent brain white matter hyperintensities to be predominantly progressive in nature. The absence of a control group precludes definitive conclusions about the nature of these changes or if their degree is beyond normal aging.

Visuospatial impairment in Parkinson's disease: the role of laterality.

Asymmetry is one of the unique and mysterious features of Parkinson's disease (PD). Motor symptoms develop unilaterally either on the left (LPD) or the right side (RPD). Incongruent data are available whether the side of onset has an impact on cognition in PD. The objective of this study is to compare the visuospatial performance of RPD and LPD patients. Seventy-one non-demented, non-depressive and right-handed patients were categorized into RBD (n = 36) and LPD (n = 35) groups. Rey-Osterrieth Complex Figure Test (ROCF) was evaluated by both the Taylor's and Loring's scoring systems. Subsequently, we also performed subgroup analyses on patients having short disease duration (≤5 years, 15 RBD and 15 LPD patients). The standard analysis of ROCF (Taylor's system) did not reveal any differences; however, the utilization of the Loring's system demonstrated that LPD patients had significantly worse visuospatial performance than the RPD subjects (3.0 vs. 2.0 points, median, p = 0.002). Correlation between the number of spatial errors and the degree of asymmetry was significant (r = -0.437, p = 0.001). However, this difference could not be observed in PD patients with short disease duration. LPD patients had worse visuospatial performance than the RPD subjects and the number of errors tightly correlated with the degree of asymmetry and long disease duration.

[Diagnosis and therapy for neurocognitive disorders in Parkinson's disease]. / Neurokognitív zavarok diagnosztizálási és kezelési lehetoségei Parkinson-kórban.

In the present review the recent developments in the definitions of neurocognitive disorders associated with Parkinson's disease are summarized including the possibilities for screening and treating. For a long time, the recognition of neurocognitive disorders associated in patients with Parkinson's disease was unsatisfactory due to the heterogeneity of definitions. The recently developed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) introduced the definitions of mild and major neurocognitive disorders instead of mild cognitive impairment and dementia. The new DSM-5 definitions are clinically well applicable; therefore, the validation of the most frequent screening tests (Mini-Mental State Examination; Addenbrooke's Cognitive Examination; Montreal Cognitive Assessment; Mattis Dementia Rating Scale) is warranted. Based on a Hungarian sample of 295 patients with Parkinson's disease, the cut-off scores having the best discriminative values are highly dependent on education years (Addenbrooke's Cognitive Examination: 0-8 years of education: 82.5 points, 9-12 years of education: 83.5 points, and ≥13 years of education: 84.5 points; Mini-Mental State Examination: 26.5-27.5-28.5 points, Montreal Cognitive Assessment: 23.5-24.5-24.5 points, Mattis Dementia Rating Scale: 138.5-139.5-139.5 points, respectively).

[EARLIER AND MORE EFFICIENTLY: THE ROLE OF DEEP BRAIN STIMULATION IN PARKINSON'S DISEASE: PRESERVING THE WORKING CAPABILITY]. / KORÁBBAN ÉS HATÉKONYABBAN: A MÉLY AGYI STIMULÁCIÓ SZEREPE A MUNKAKÉPESSÉG MEGORZÉSÉBEN.

BACKGROUND: The recently published "EarlyStim" study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. METHODS: We reviewed the data of 39 young (< 60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job ("Job+" group, n = 15) and retired patients (without active job, "Job-" group, n = 24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. RESULTS: As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p < 0.01, McNemar test). CONCLUSION: Although our retrospective study has several limitations, our results fit well with the conclusions of "EarlyStim" study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.

[VALIDATION OF THE HUNGARIAN UNIFIED DYSKINESIA RATING SCALE]. / AZ EGYSÉGESÍTETT DYSKINESIA-PONTOZÓSKÁLA MAGYAR NYELVI VALIDÁCIÓJA.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) was published in 2008. It was designed to be simultaneous valid, reliable and sensitive to therapeutic changes. The Movement Disorder Society organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new UDysRS and its validation process into Hungarian. METHODS: After the translation of UDysRS into Hungarian and back-translated into English, it was reviewed by the UDysRS translation administration team. Subsequent cognitive pretesting was conducted with ten patients. For the large field testing phase, the Hungarian official working draft version of UDysRS was tested with 256 patients with Parkinson's disease having dyskinesia. Confirmatory factor analyses (CFA) determined whether the factor structure for the valid Spanish UDysRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the Spanish-language version. RESULTS: For the Hungarian UDysRS the CFI was 0.98. CONCLUSION: The overall factor structure of the Hungarian version was consistent with that of the Spanish version based on the high CFIs for the UDysRS in the CFA; therefore, this version was designated as the Official Hungarian Version Of The UDysRS.

[The impact of levodopa-carbidopa intestinal gel on health-related quality of life in Parkinson's disease]. / Levodopa/carbidopa intestinalis gél kezelés hatása az életminoségre.

BACKGROUND: The levodopa/carbidopa intestinal gel (LCIG) therapy can improve the severe fluctuations associated with advanced Parkinson's disease (PD). Our aim was to assess the improvement in the health related quality of life of PD patients treated with LCIG at University of Pécs. METHODS: Eight PD patients were evaluated (age: 68.1 ± 4.4 years, disease duration: 14.5 ± 6.2 years, duration of fluctuations: 8.9 ± 3.1 years). Before the initiation of LCIG treatment and 6 and 12 months later, the health-relat- ed quality of life (PDQ-39 and EQ-5D-5L), severity of PD- related symptoms (MDS-UPDRS, Hoehn-Yahr Scale, Clinical Global Improvement--Severity) and major non-motor symptoms (PD Sleep Scale 2nd version: PDSS-2, Epworth Scale and Beck Depression Inventory: BDI) were assessed. RESULTS: Health-related quality life improved after LCIG treatment measured by both EQ-5D-5L (from 0.257 to 0.662, p = 0.009) and PDQ-39 (from 34 to 26 points, p = 0.038). Meanwhile PD-related symptoms (MDS-UPDRS total score: from 105 points to 68 points, p < 0.05) sleep quality (PDSS-2: from 25 to 22 points, p < 0.05), daytime sleepiness (Epworth: from 12 to 7 points, p < 0.05) and depression (BDI: from 20 to 15 points, p < 0.05) also improved. Median ON time improved form 4.5 hours to 10.0 hours; whereas, the OFF time decreased from 4.5 to 0.5 hours (p < 0.05). CONCLUSION: Both the quality of life and the clinical fea- tures of PD can be improved by LCIG treatment in advanced PD.

[VALIDATION OF THE HUNGARIAN MDS-UPDRS: WHY DO WE NEED A NEW PARKINSON SCALE?]. / AZ MDS-UPDRS MAGYAR VALIDáCIóJA: MIéRT SZüKSéGES UJABB PARKINSON-PONTOZOSKáLA?

BACKGROUND: The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian. METHODS: Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson's disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the English-language version. RESULTS: For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥ 0.94. CONCLUSION: The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDS-UPDRS in the CFA; therefore, this version was designated as the "OFFICIAL GUNGARIAN VERSION OF THE MDS-UPDRS'.

Diabetic neuropathies: diagnosis and management.

INTRODUCTION: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. METHODS: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. CONCLUSION: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective.

[Effective, safe stroke prevention with novel oral anticoagulants in patients with atrial fibrillation. Focus on dabigatran]. / Hatékony, biztonságos stroke-prevenció pitvarfibrilláció esetén új típusú orális antikoagulánsokkal. Fókuszban a dabigatran.

Non-valvular AF is the most common cardiac arrhytmia. Its incidence increases with age. AF is an independent risk factor for ischaemic stroke, representing a five times higher risk for it, associated with a high mortality rate. Beside AF, there are several other risk factors which influence the risk of stroke. Stroke risk calculator can be used to assess the risk of patient having a stroke. The most endangered group of patients with AF are those who have already suffered from cerebrovascular event. The only effective medication for prevention of stroke due to AF had been the application of vitamin K antagonists (VKA) which considerably decrease the rate of ischaemic event in a patient with AF providing that the INR is in the therapeutic range. VKA have several limitations of use in clinical practice and the fear of bleeding complications results an underusing of these drugs. Only 50% of all patients treated with VKA reaches the therapeutic range of INR. The breakthrough of prevention of stroke in recent years is undisputedly the coming out of novel oral anticoagulants (NOACs, thrombin and Xa-factor inhibitors). Recent studies suggest that these novel drugs prove the same efficacy as VKA drugs, furthermore dabigatran in a dose of 2 x 150 mg or apixaban in 2 x 5 mg was statistically superior to warfarin in the prevention of stroke. NOACs have shown a large reduction in intracranial hemorrhage compared with warfarin. They are given as a fixed dose and do not require persistent monitoring making them much more convenient. NOACs at guidelines of European Society of Cardiology act as a preferable drugs in case of ischaemic stroke with AF Probably the extended use of NOACs in clinical practice will be the mainstream of stroke prevention in the future.

[Treatment of dystonia by deep brain stimulation: a summary of 40 cases]. / Dystonia kezelése mély agyi stimulációval: 40 eset tapasztalatainak osszefoglalása.

BACKGROUND: Bilateral pallidal deep brain stimulation (DBS) is an established treatment option for primary generalized and segmental dystonia. In the present study we evaluated the results of our dystonia patients treated by DBS. METHODS: The surgical results of forty consecutive dystonia patients underwent DBS implantation were analyzed (age: 43.7 +/- 17.7 years; sex: 22 men; etiology: 24 primary and 16 secondary dystonia; topography: 24 generalized, 12 segmental and four hemidystonia; disease duration: 16.1 +/- 9.3 years). Severity of dystonia measured by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and health-related quality of life measured by EQ-5D scale were obtained preoperatively and compared to the scores obtained at postoperative six months and subsequent yearly follow-ups. The average follow-up lasted 2.5 years (median, 0.5-8 years). In all cases the BFMDRS scores were re-evaluated by a rater blinded to the treatment. Treatment responsiveness was defined as an at least 25% improvement on the BFMDRS scores. Non-parametric Mann-Whitney, McNemar and Kruskal-Wallis tests were applied to test statistical significance. RESULTS: Severity of dystonia improved from 31 to 10 points (median, 68% improvement, p < 0.01) in the primary dystonia group, whereas in secondary dystonia these changes were statistically insignificant (improvement from 40 to 31.5 points, 21.2%, p > 0.05). However, the health-related quality of life significantly improved in both groups (primary dystonia: 0.378 vs. 0.788 and secondary dystonia: 0.110 vs. 0.388, p < 0.01). Significantly more patients in the primary dystonia group responded to DBS treatment than those in the secondary dystonia group (83.3% vs. 37.5%, p < 0.01). CONCLUSION: Our results are in accordance with previously published international findings demonstrating that DBS is a highly effective and long-lasting treatment option for primary dystonia. DBS is considerably less efficient in secondary dystonia; however, it still has a high impact on the quality of life presumably due to its pain-relieving effect.

Small Fiber Neuropathy: Clinicopathological Correlations.

Small fiber neuropathy develops due to the selective damage of the thin fibers of peripheral nerves. Many common diseases can cause this condition, including diabetes, infections, autoimmune and endocrine disorders, but it can occur due to genetic alterations, as well. Eighty-five skin biopsy-proven small-fiber neuropathy cases were analyzed. Forty-one (48%) cases were idiopathic; among secondary types, hypothyreosis (9.4%), diabetes mellitus (7%), cryoglobulinemia (7%), monoclonal gammopathy with unproved significance (4.7%), Sjögren's disease (3%), and paraneoplastic neuropathy (3%) were the most common causes. Two-thirds (68%) of the patients were female, and the secondary type started 8 years later than the idiopathic one. In a vast majority of the cases (85%), the distribution followed a length-dependent pattern. Intraepidermal fiber density was comparable in idiopathic and secondary forms. Of note, we found significantly more severe pathology in men and in diabetes. Weak correlation was found between patient-reported measures and pathology, as well as with neuropathic pain-related scores. Our study confirmed the significance of small fiber damage-caused neuropathic symptoms in many clinical conditions, the gender differences in clinical settings, and pathological alterations, as well as the presence of severe small fiber pathology in diabetes mellitus, one of the most common causes of peripheral neuropathy.

Minimal clinically important difference on the Motor Examination part of MDS-UPDRS.

BACKGROUND: Recent studies increasingly utilize the Movement Disorders Society Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, the minimal clinically important difference (MCID) has not been fully established for MDS-UPDRS yet. OBJECTIVE: To assess the MCID thresholds for MDS-UPDRS Motor Examination (Part III). METHODS: 728 paired investigations of 260 patients were included. At each visit both MDS-UPDRS and Clinician-reported Global Impression-Improvement (CGI-I) scales were assessed. MDS-UPDRS Motor Examination (ME) score changes associated with CGI-I score 4 (no change) were compared with MDS-UPDRS ME score changes associated with CGI-I score 3 (minimal improvement) and CGI-I score 5 (minimal worsening). Both anchor- and distribution-based techniques were utilized to determine the magnitude of MCID. RESULTS: The MCID estimates for MDS-UPDRS ME were asymmetric: -3.25 points for detecting minimal, but clinically pertinent, improvement and 4.63 points for observing minimal, but clinically pertinent, worsening. CONCLUSIONS: MCID is the smallest change of scores that are clinically meaningful to patients. These MCID estimates may allow the judgement of a numeric change in MDS-UPDRS ME on its clinical importance.

Minimal Clinically Important Difference on Parkinson's Disease Sleep Scale 2nd Version.

Background and Aims. The aim of the present study was to determine the estimates of minimal clinically important difference for Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score and dimensions. Methods. The subject population consisted of 413 PD patients. At baseline, MDS-UPDRS, Hoehn-Yahr Scale, Mattis Dementia Rating Scale, and PDSS-2 were assessed. Nine months later the PDSS-2 was reevaluated with the Patient-Reported Global Impression Improvement Scale. Both anchor-based techniques (within patients' score change method and sensitivity- and specificity-based method by receiver operating characteristic analysis) and distribution-based approaches (effect size calculations) were utilized to determine the magnitude of minimal clinically important difference. Results. According to our results, any improvements larger than -3.44 points or worsening larger than 2.07 points can represent clinically important changes for the patients. These thresholds have the effect size of 0.21 and -0.21, respectively. Conclusions. Minimal clinically important differences are the smallest change of scores that are subjectively meaningful to patients. Studies using the PDSS-2 as outcome measure should utilize the threshold of -3.44 points for detecting improvement or the threshold of 2.07 points for observing worsening.

Deep Brain Stimulation Can Preserve Working Status in Parkinson's Disease.

Objectives. Our investigation aimed at evaluating if bilateral subthalamic deep brain stimulation (DBS) could preserve working capability in Parkinson's disease (PD). Materials. We reviewed the data of 40 young (<60 year-old) PD patients who underwent DBS implantation and had at least 2 years of follow-up. Patients were categorized based on their working capability at time of surgery: "active job" group (n = 20) and "no job" group (n = 20). Baseline characteristics were comparable. Quality of life (EQ-5D) and presence of active job were evaluated preoperatively and 2 years postoperatively. Results. Although similar (approximately 50%) improvement was achieved in the severity of motor and major nonmotor symptoms in both groups, the postoperative quality of life was significantly better in the "active job" group (0.687 versus 0.587, medians, p < 0.05). Majority (80%) of "active job" group members were able to preserve their job 2 years after the operation. However, only a minimal portion (5%) of the "no job" group members was able to return to the world of active employees (p < 0.01). Conclusions. Although our study has several limitations, our results suggest that in patients with active job the appropriately "early" usage of DBS might help preserve working capability and gain higher improvement in quality of life.

Bilateral Subthalamic Stimulation can Improve Sleep Quality in Parkinson's Disease.

BACKGROUND: Sleep problems are among the most common non-motor symptoms of Parkinson's disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the original PDSS by adding more items on different aspects of sleep problems, making it a more robust tool to evaluate the severity of sleep disturbances. However, previous studies on deep brain stimulation (DBS) have not used the PDSS-2. OBJECTIVE: To determine if the PDSS-2 could detect improvement reliably in sleep problems after bilateral subthalamic nucleus DBS for PD. METHODS: In this prospective study, 25 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were specifically measured by PDSS-2. RESULTS: Total score of MDS-UPDRS improved from 81 (median, interquartile-range: 63-103) to 55 points (median, IQR: 46-75, p <  0.001). Health-related quality of life, measured by PDQ-39, also improved from 29 (IQR: 18-40) to 15 (IQR: 9-28) points (p = 0.002). Most domains of NMSS also improved. At baseline 13 patients reported sleep problems, but 1 year after DBS implantation only 3 did (p = 0.012). Although only 6 out of 15 items showed a significant decrease after DBS implantation, the total score of PDSS-2 decreased from 24 (IQR: 17-32) to 10 (IQR: 7-18) points (P <  0.001). CONCLUSIONS: Based on our results, PDSS-2 can detect improvements in sleep quality reliably after DBS implantation.