White matter hyperintensities associated with impulse control disorders in Parkinson's Disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are increasingly recognized as clinically significant non-motor features that potentially impair the quality of life. White matter hyperintensities (WMHs), detected by magnetic resonance imaging, are frequently observed in PD and can be associated with both motor- and certain non-motor symptoms. Given the limited number of non-motor features studied in this context, our aim was to reveal the potential association between the severity of WMHs and ICDs in PD. Fluid-attenuated inversion recovery magnetic resonance images were retrospectively evaluated in 70 patients with PD (48 males; 59.3 ± 10.1 years). The severity of WMHs was assessed by Fazekas scores and by the volume and number of supratentorial WMHs. ICDs were evaluated using the modified Minnesota Impulsive Disorders Interview. Significant interaction between age and the severity of WMHs was present for ICDs. In our younger patients (< 60.5 years), severity of WMHs was positively associated with ICDs (p = 0.004, p = 0.021, p < 0.001 and p < 0.001, respectively for periventricular white matter and total Fazekas scores and the volume and number of WMHs). Our study supports the hypothesis that WMHs of presumed vascular origin may contribute to ICDs in PD. Future prospective studies are needed to assess the prognostic relevance of this finding.

Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation.

BACKGROUND: Several pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. OBJECTIVE: We conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. MATERIALS AND METHODS: A total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society-sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson's Disease Questionnaire (PDQ-39) were assessed. RESULTS: According to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. CONCLUSIONS: Directional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

Dystonia management across Europe within ERN-RND: current state and future challenges.

BACKGROUND: Since the first European-wide evaluation of dystonia management in 2016, several efforts have been made to improve dystonia-care. One of these was the development of the Dystonia Disease Group as a part of the European Reference Network for Rare Neurological Diseases (ERN-RND) that implemented several initiatives based on the recommendations made in 2016. AIM: To evaluate the current state of dystonia management across Europe. METHODS: Twenty-four countries were surveyed via 62 dystonia-experts from 44 ERN-RND-related centers. RESULTS: Dystonia-experts for adult patients were available in all surveyed countries. However, almost half of the countries evaluated accessibility as merely 'satisfactory'. Access to genetic and neurophysiological testing was challenging to varying degrees in over half of countries. Main oral medications and botulinum toxin were available in all countries. Deep brain stimulation (DBS) was easily accessible in one-third of the countries. Dystonia research was conducted in 20/24 countries. Trainings on dystonia for general practitioners (GPs) were available in 11/24 countries. However, lack of trainings for other professionals was almost general. For pediatric dystonia, experts and specific training were available in over half of the countries. CONCLUSIONS: In this overview, we present the current state of dystonia management within ERN-RND. Management has slightly improved since 2016 in several fields, including diagnostics, availability of DBS, and research. The results highlight that future challenges in dystonia management are accessibility of experts, and diagnostic tools and treatments, education on adult and childhood dystonia, and optimization of referral pathways. These findings are important for improving dystonia care across Europe.

Potential clinical and economic benefits of remote deep brain stimulation programming.

Deep brain stimulation (DBS) teleprogramming may help reducing travel-related and other financial burdens for patients and maintaining DBS care in special situations. To determine travel-related burdens of DBS patients and explore effects of COVID-19 on DBS care. Travel- and visit-related data of 319 patients were retrospectively analyzed for the first year, five years, and ten years after initiating DBS. Frequencies of in-person and telemedicine visits over the 18-month periods just before and after the outbreak of COVID-19 in Hungary were also compared. Average travel distance during an in-person visit was 415.2 ± 261.5 km, while average travel time was 342.1 ± 199.4 min. Travel costs for the first year, five years, and ten years were 151.8 ± 108.7, 461.4 ± 374.6, and 922.7 ± 749.1 Euros, respectively. Travel distance, age, and type and severity of disease could help identify patients who would particularly benefit from teleprogramming. We detected a significant decrease in the number of visits during COVID-19 pandemic (from 3.7 ± 2.1 to 2.4 ± 2.7; p < 0.001) which mainly resulted from the decreased frequency of in-person visits (3.6 ± 2.0 vs. 1.7 ± 1.8; p < 0.001). Our results support the introduction of DBS teleprogramming in Hungary which could save money and time for patients while maintaining a secure delivery of DBS.

[Telecare in Parkinson's disease: A nationwide survey among Hungarian neurologists]. / Távellátás Parkinson-kórban: országos felmérés a magyar neurológusok körében.

Background and purpose: COVID-19 has made providing in-person care difficult. In most countries, including Hungary, telemedicine has partly served as a resolution for this issue. Our purpose was to explore the effects of COVID-19 on neurological care, the knowledge of neurology specialists on telemedicine, and the present state of telecare in Hungary, with a special focus on Parkinson's disease (PD). Methods: Between July and October 2021, a nationwide online survey was conducted among actively practicing Hungarian neurology specialists who were managing patients with PD. Results: A total of 104 neurologists were surveyed. All levels of care were evaluated in both publicly funded and private healthcare. Both time weekly spent on outpatient specialty consultation and the number of patients with PD seen weekly significantly decreased in public healthcare, while remained almost unchanged in private care (p<0.001); higher portion of patients were able to receive in-person care in private care (78.8% vs. 90.8%, p<0.001). In telecare, prescribing medicines has already been performed by the most (n=103, 99%). Electronic messages were the most widely known telemedicine tools (n=98, 94.2%), while phone call has already been used by most neurologists (n=95, 91.3%). Video-based consultation has been more widely used in private than public care (30.1% vs. 15.5%, p=0.001). Teleprocedures were considered most suitable for monitoring progression and symptoms of Parkinson's disease and evaluating the need for adjustments to antiparkinsonian pharmacotherapy. Conclusion: COVID-19 has had a major impact on the care of patients with PD in Hungary. Telemedicine has mitigated these detrimental effects; however, further developments could make it an even more reliable component of care.

The effects of CRF and the urocortins on the hippocampal acetylcholine release in rats.

Corticotropin-releasing factor (CRF) and the urocortins (Ucn1, Ucn2 and Ucn3) are structurally related neuropeptides which act via two distinct CRF receptors, CRF1 and CRF2, with putatively antagonistic effects in the brain. CRF and Ucn1 activate both CRF1 and CRF2, while Ucn2 and Ucn3 activate selectively CRF2. The aim of the present study was to investigate the effects of CRF, Ucn1, Ucn2 and Ucn3 on the hippocampal acetylcholine release through which they may modulate cognitive functions, including attention, learning and memory. In this purpose male Wistar rats were used, their hippocampus was isolated, dissected, incubated, superfused and stimulated electrically. The hippocampal slices were first pretreated with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B, and then treated with non-selective CRF1 agonists, CRF or Ucn1, and selective CRF2 agonists, Ucn2 or Ucn3. The hippocampal acetylcholine release was increased significantly by CRF and Ucn1 and decreased significantly by Ucn2 and Ucn3. The increasing effect of CRF and Ucn1 was reduced significantly by antalarmin, but not astressin2B. In contrast, the decreasing effect of Ucn2 and Ucn3 was reversed significantly by the selective CRF2, but not the selective CRF1 antagonist. Our results demonstrate that CRF and Ucn1 stimulate the hippocampal acetylcholine release through CRF1, whereas Ucn2 and Ucn3 inhibit the hippocampal acetylcholine release through CRF2. Therefore, the present study suggests the existence of two apparently opposing CRF systems in the hippocampus, through which CRF and the urocortins might modulate cholinergic activity and thereby cognitive functions.

Trimetazidine Use in Parkinson's Disease: Is It a Resolved Problem?

Trimetazidine (TMZ), an antianginal drug, can worsen the symptoms of movement disorders, therefore, the European Medicines Agency (EMA) recommended avoiding the use of this drug in Parkinson's disease (PD). We investigated the impact of this recommendation on the observed trend of TMZ use in PD in Hungary from 2010 to 2016 by conducting a nationwide, retrospective study of health administrative data of human subjects. Interrupted time series analyses were performed to explore changes in user trends after the EMA recommendations. We found that TMZ use in PD decreased by 6.56% in each six-month interval after the EMA intervention [a change in trend of -530.22, 95% confidence interval (CI) = -645.00 to -415.44, p < 0.001 and a decrease in level of -567.26, 95% CI = -910.99 to -223.53, p = 0.005 12 months postintervention]. TMZ discontinuation was the highest immediately after the intervention, however, its rate slowed down subsequently (a change in trend of -49.69, 95% CI = -85.14 to -14.24, p = 0.11 without significant level effects). The rate of new TMZ prescriptions did not reduce significantly, therefore, the decreased overall use was mainly attributable to the increased rate of discontinuation only. The main indications for TMZ use were circulatory system disorders, especially angina pectoris, however, off-label utilization was also considerable (40%). The EMA recommendations on TMZ use seem to be only moderately effective in Hungary. Although the number of patients with PD on the drug modestly decreased after the EMA restrictions, TMZ is still widely used in PD for both on-label and off-label indications.

Fast 3 T nigral hyperintensity magnetic resonance imaging in Parkinson's disease.

The absence of nigral hyperintensity is a promising MR marker for Parkinson's disease (PD), but its small size imposes limitations on its routine use. Our aim was to compare Multi Echo Data Image Combination (MEDIC), segmented echo-planar imaging (EPISEG) and fluid-attenuated inversion recovery (FLAIR) sequences, as well as both magnitude (MAG) and susceptibility-weighted imaging (SWI) reconstructions of single-echo gradient echo for nigral hyperintensity imaging. Twenty-five healthy and twenty PD subjects were included. Sensitivity to motion artefacts, confidence of the radiologist in interpretation, rate of nondiagnostic scans and diagnostic accuracy were assessed. EPISEG was less motion-sensitive than MEDIC, MAG, and SWI, while FLAIR was less motion-sensitive than MAG and SWI. The reviewers were more confident when using EPISEG compared to any other techniques and MEDIC was superior to FLAIR. The proportions of nondiagnostic scans were lower for EPISEG than for other sequences. The best diagnostic performance was achieved for EPISEG (sensitivity = 65%, specificity = 96%). Using EPISEG, the absence of nigral hyperintensity in PD was associated with higher Hoehn-Yahr stage and MDS-UPDRS II + III. Nigral hyperintensity may be intact at the very early stages of PD. The promising properties of EPISEG may help the transfer of nigral hyperintensity imaging into daily clinical practice.

Complications of Ileal Conduits after Radical Cystectomy: Interventional Radiologic Management.

Since their introduction into clinical practice in the 1950s, ileal conduits have been the most common type of urinary diversion used after radical cystectomy worldwide. Although ileal conduits are technically simpler to construct than other forms of urinary diversion, a variety of complications can occur in the early and late postoperative periods. Early complications include urine leakage, urinary obstruction, postoperative fluid collection (eg, urinoma, hematoma, lymphocele, or abscess), and fistula formation. Late complications include ureteroileal anastomotic stricture, stomal stenosis, conduit stenosis, and urolithiasis. Although not directly related to ileal conduits, ureteroarterial fistula can occur in patients with an ileal conduit. Interventional radiologists can play a pivotal role in diagnosis and management of these complications by performing image-guided minimally invasive procedures. In this article, the authors review the surgical anatomy of an ileal conduit and the underlying pathophysiology of and diagnostic workup for complications related to ileal conduits. The authors also discuss and illustrate current approaches to interventional radiologic management of these complications, with emphasis on a collaborative approach with urologists or endourologists to best preserve patients' renal function and maintain their quality of life. ©RSNA, 2020.

The Impact of Trimetazidine on Disease Severity and Quality of Life in Parkinson's Disease.

Trimetazidine is contraindicated in movement disorders, however, a not negligible part of trimetazidine users is still patients with Parkinson's disease (PD). The present study aimed to objectively determine the impact of trimetazidine on the severity of symptoms and the health-related quality of life of patients with PD by measuring changes after its withdrawal. A consecutive series of 42 patients with PD using trimetazidine underwent detailed neurological and neuropsychological assessments at baseline and three months after the discontinuation of trimetazidine. Clinically relevant improvements were achieved with discontinuation of trimetazidine according to changes in scores of each part of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (Part I: -25.7%, p < 0.001; Part II: -23.8%, p < 0.001; Part III: -28.5%, p < 0.001; Part IV: -30.1%, p = 0.004) and total scores of the Non-Motor Symptoms Scale (-25.6%, p = 0.004) and the Montgomery-Asberg-Depression Rating Scale (-20.1%, p = 0.001). Benefits resulting from the withdrawal of the drug also manifested in the improvement of the health-related quality of life based on changes in the summary index of the 39-item Parkinson's Disease Questionnaire (-18.2%, p = 0.031). Our results provide clinical rationale for strictly avoiding the use of trimetazidine in PD. Discontinuation of trimetazidin results in clinically relevant improvements in Parkinsonian symptoms.

Minimal Clinically Important Differences for Burke-Fahn-Marsden Dystonia Rating Scale and 36-Item Short-Form Health Survey.

BACKGROUND: Although an increasing number of trials are reported on the treatment of generalized or segmental isolated dystonia, the minimal clinically important difference thresholds for the most frequently reported outcome measures are still undetermined. OBJECTIVES: To estimate the minimal clinically important difference for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey in generalized or segmental dystonia. METHODS: A total of 898 paired examinations of 198 consecutive patients, aged >18 years, with idiopathic and inherited (torsin family 1 member A positive) segmental and generalized isolated dystonia were analyzed. To calculate the minimal clinically important difference thresholds, both anchor- and distribution-based methods were used simultaneously. RESULTS: Any improvement >16.6% or worsening larger than 21.5% on the Burke-Fahn-Marsden Dystonia Rating Scale indicates a minimal, yet clinically relevant, change. Threshold values for the Burke-Fahn-Marsden Dystonia Disability Scale were 0.5 points for both decline and improvement. Cut-off scores for the Physical Component Summary, the Mental Component Summary, and the Global (Total or Overall) Score of the 36-Item Short-Form Health Survey were 5.5 and 5.5, 6.5 and 7.5, and 7.5 and 8.5 points for clinically meaningful improvement and deterioration, respectively. CONCLUSIONS: The minimal clinically important difference represents the smallest change in an outcome measure that is meaningful to patients. Our estimates for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey may allow more reliable judgment of the clinical relevance of different treatments for segmental and generalized isolated dystonia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Which Scale Best Detects Treatment Response of Tremor in Parkinsonism?

BACKGROUND: Several scales are available for rating the severity of tremor at present. However, the sensitivity to change of these instruments has remained to be clarified. OBJECTIVE: To compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments. METHODS: Enrolling subjects with parkinsonism associated with tremor, we analyzed two scenarios: (1) tremor changes associated with acute levodopa challenge (n = 287) and (2) a 12-month outcome of different treatment options (n = 512) including deep brain stimulation (n = 146), levodopa/carbidopa intestinal gel infusion (n = 30), and initiating (n = 63) or adjusting oral antiparkinsonian medication (n = 273). Changes in tremor scales were assessed by effect size values (Cohen's d and eta-square). RESULTS: Part B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen's d = -1.04, η2 = 0.12). However, Part A of the Fahn-Tolosa-Marin Tremor Rating Scale showed the highest effect size, which was a small one (Cohen's d = -0.33, η2 = 0.03), for detecting a treatment-related change in the severity of tremor during long-term follow-up. CONCLUSIONS: The Fahn-Tolosa-Marin Tremor Rating Scale has a better ability to capture changes due to levodopa challenge or antiparkinsonian treatment than MDS-UPDRS Part III or MDS-UPDRS Tremor Scale.

The Parkinson's Disease Composite Scale Is Adequately Responsive to Acute Levodopa Challenge.

BACKGROUND: The Parkinson's Disease Composite Scale (PDCS) is a recently developed easy-to-use tool enabling a timely but comprehensive assessment of Parkinson's disease (PD)-related symptoms. Although the PDCS has been extensively validated, its responsiveness to acute levodopa challenge has not been demonstrated yet. OBJECTIVE: To investigate the correlation between changes in the motor examination part of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the PDCS motor scores during acute levodopa challenge and calculate a cutoff range on the PDCS indicating clinically relevant improvement. METHODS: A consecutive series of 100 patients with parkinsonism were assessed using the motor examination sections of the MDS-UPDRS and the PDCS at least 12 hours after the last levodopa dose and after the administration of a single dose of a suprathreshold immediate formulation of levodopa/benserazide reaching the "best ON." Results. There was a high correlation between changes in the MDS-UPDRS and the PDCS motor scores (Spearman's rho = 0.73, p < 0.001). Receiver operating characteristic analysis revealed that a 14.6%-18.5% improvement in the PDCS motor scores corresponds to a 20-30% improvement in the MDS-UPDRS motor examination. CONCLUSIONS: The PDCS can reliably and adequately respond to an acute levodopa challenge. Any improvements in PDCS motor scores exceeding the 14.6-18.5% threshold could represent a clinically relevant response to levodopa.

Screening for Problematic Internet Use May Help Identify Impulse Control Disorders in Parkinson's Disease.

BACKGROUND: Impulse control disorders in Parkinson's disease (PD) represent emerging problems with potentially devastating consequences. The standard screening methods for impulse control disorders are clinically imperfect. Although it is rarely reported, many patients utilize the Internet to fulfill their compulsive behaviors because of its easy accessibility. We designed a study to test the hypothesis that an active screening for excessive Internet use and Internet addiction might improve the sensitivity of identification of impulse control disorders. METHODS: The standard screening method included the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease and the modified Minnesota Impulsive Disorders Interview. In the second round, the Problematic Internet Use Questionnaire was also assessed for detecting excessive Internet use. RESULTS: While the standard approach identified 19 patients out of 106 (17.9%) with any type of impulse control disorders, screening for the problematic Internet use detected 29 patients with impulse control disorders (27.4%) having significantly better efficacy over the standard method (p = 0.004, the McNemar test). CONCLUSIONS: Our study suggests that the screening for problematic Internet use by the Problematic Internet Use Questionnaire is an effective, feasible, and easy-to-use add-on method for identifying PD patients with impulse control disorders more efficiently and probably at earlier stages.

[Selection of the optimal device-aided therapy in Parkinson's disease]. / Elorehaladott Parkinson-kór kezelési lehetoségei: az optimális terápia kiválasztásának szempontjai.

For the treatment of advanced Parkinson's disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary. Although they may have similar impact on the health-related quality of life and disabilities associated with the disease, they have different indications, and inclusion- and exclusion criteria. Consequently, the patient population treated with DBS and LCIG may be different. In the present review, the authors try to help the process of selection of the optimal device-aided therapy for the patients with advanced Parkinson's disease.

Changes in striatal dopamine release and locomotor activity following acute withdrawal from chronic nicotine are mediated by CRF1, but not CRF2, receptors.

The aim of the present study was to investigate the participation of corticotropin-releasing factor (CRF) receptors (CRF1 and CRF2) in the alterations of the dorsal and ventral striatal dopamine release and the vertical and horizontal locomotor activity observed in rats following chronic nicotine treatment and consequent acute withdrawal. In this purpose, male Wistar rats were exposed to repeated intraperitoneal (ip) injection with nicotine or saline solution for 7 days. On the 8th day or the 9th day the rats were injected intracerebroventricularly (icv) with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B or saline solution. Thirty minutes after the icv injection the changes of the horizontal and vertical locomotor activity were recorded in an in vivo conducta system. Immediately after the behavioral recordings the changes of the dorsal and ventral striatal dopamine release were determined in an in vitro superfusion system. On the 8th day, the horizontal and vertical locomotor activities and the dorsal and ventral striatal dopamine releases increased significantly in nicotine-treated rats, compared to the saline-treated ones. On the 9th day, the horizontal locomotor activity and the dorsal striatal dopamine release increased significantly, whereas the vertical locomotor activity and the ventral striatal dopamine release decreased significantly in nicotine-treated rats, compared to the saline-treated ones. All the changes observed were attenuated significantly by antalarmin, but not astressin2B. The present study demonstrates that the changes of striatal dopamine release and locomotor activity observed following chronic nicotine treatment and consequent acute withdrawal are mediated by CRF1, but not CRF2, receptor.