The neural correlates of mental fatigue and reward processing: A task-based fMRI study.

Increasing time spent on the task (i.e., the time-on-task (ToT) effect) often results in mental fatigue. Typical effects of ToT are decreasing levels of task-related motivation and the deterioration of cognitive performance. However, a massive body of research indicates that the detrimental effects can be reversed by extrinsic motivators, for example, providing rewards to fatigued participants. Although several attempts have been made to identify brain areas involved in mental fatigue and related reward processing, the neural correlates are still less understood. In this study, we used the psychomotor vigilance task to induce mental fatigue and blood oxygen-level-dependent functional magnetic resonance imaging to investigate the neural correlates of the ToT effect and the reward effect (i.e., providing extra monetary reward after fatigue induction) in a healthy young sample. Our results were interpreted in a recently proposed neurocognitive framework. The activation of the right middle frontal gyrus, right insula and right anterior cingulate gyrus decreased as fatigue emerged and the cognitive performance dropped. However, after providing an extra reward, the cognitive performance, as well as activation of these areas, increased. Moreover, the activation levels of all of the mentioned areas were negatively associated with reaction times. Our results confirm that the middle frontal gyrus, insula and anterior cingulate cortex play crucial roles in cost-benefit evaluations, a potential background mechanism underlying fatigue, as suggested by the neurocognitive framework.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

BACKGROUND: Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. PURPOSE: To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. STUDY TYPE: Prospective. POPULATION: Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). FIELD STRENGTH/SEQUENCE: Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. ASSESSMENT: MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. RESULTS: In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3 , η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3 , η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). DATA CONCLUSION: Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Urinary titin in myotonic dystrophy type 1.

INTRODUCTION/AIMS: Urinary titin, an easy-to-obtain marker, has been investigated in muscular dystrophies, but not in myotonic dystrophy type 1 (DM1). We investigated the role of titin as a biomarker of muscle injury in DM1. METHODS: We compared the urinary titin N-fragment/creatinine ratio in 29 patients with DM1 vs. 30 healthy controls. We also recorded clinical data such as muscle strength, serum creatine kinase, DM1-related outcome measures, and the 20-item DM1-activ questionnaire. The severity of the disease was graded using the Muscular Impairment Rating Scale (MIRS). RESULTS: The titin/creatinine ratio was significantly higher in the urine samples of DM1 patients than of healthy controls (median ± mean absolute deviation [MAD]: 39.313 ± 26.546 vs. 6.768 ± 5.245 pmol/mg creatinine; P < .001), and was related to muscle impairment graded by MIRS (τ = 0.503, P = .038). DISCUSSION: Urinary titin may be a biomarker for DM1. Long-term follow-up of DM1 patients is needed to investigate the potential role of titin as a biomarker for disease activity and progression.

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.

Sudden gamer death: non-violent death cases linked to playing video games.

BACKGROUND AND AIMS: Internet gaming disorder (IGD) is an emerging problem. Rarely, media reports about people, who have died during playing video games, but thus far no systematic, scientific study is available about the topic. We investigated such cases, looking for common characteristics, connection between gaming and death, and the possible reasons leading to death. METHODS: Cases were collected through internet search with general keywords, with ones specific to identified cases, and by working along cross references. RESULTS: 24 cases were found: one from 1982, the others between 2002 and 2021. Twenty-three of the victims were male, age ranged from 11 to 40 years. More than half of the cases originated from Southeast Asia, and 12 deaths happened in internet cafes. Gamers played action-rich multiplayer games. In 18 cases the gaming session before death was extremely long (around a day or even several days) with minimal rest. The cause of death was pulmonary embolism in 5 cases, cerebral hemorrhage in 2 cases, most of the rest was presumably due to fatal cardiac arrhythmia. DISCUSSION: Long sedentary position and dehydration may precipitate thromboembolism, acute blood pressure elevation during gaming may promote cerebral hemorrhage, and several factors (including acute and chronic sleep deprivation, exhaustion, stress) can lead to acute autonomic dysfunction and fatal arrhythmia. CONCLUSION: Incidence of non-violent death cases linked to playing video games is presumably very low. It mostly occurs in young males and it is often characterized by extremely long gaming time.

[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 role of intravenous thrombolysis before mechanical thrombectomy in the treatment of large vessel occlusion strokes]. / A mechanikus thrombectomiát megelozo intravénás thrombolysis szerepe az akut agyi nagyérelzáródások kezelésében.

BACKGROUND AND PURPOSE: The efficacy of intravenous thrombolysis (IVT) is moderate in the proximal vascular segments of intracranial arteries, as opposed to mecha-nical thrombectomy (MT). In the management of acute ischemic stroke (AIS) caused by large vessel occlusions (LVO), IVT prior to MT is highly recommended based on the latest guidelines, but the necessity of IVT has been questioned by the latest studies of the past years. The aim of our study was to investigate and compare the efficacy and safety of direct mechanical thrombectomy (dMT) and combined therapy (CT) for patients who suffered an AIS with LVO and were treated in our department. METHODS: We investigated patients with AIS caused by LVO who were admitted up to 4.5 hours after symptom onset and underwent MT in our department between November 2017 and August 2019. Patients' data were collected in our stroke register. Patients enrolled in our study were divided into two groups depending on whether dMT or CT was used. Our primary outcome was the 30- and 90- day functional outcome measured by modified Rankin Scale (mRS). Mortality at 30- and 90- day, successful recanalization rates, and symptomatic intracranial hemorrhage were considered as secondary outcomes. RESULTS: A total of 142 patients (age: 68.3 ± 12.6 years, 53.5% female) were enrolled in our study, including 81 (57.0%) dMT cases, and 61 (43.0%) patients who received CT. The vascular risk factors and comorbidities were significantly higher in the dMT-treated group. At day 30, the rate of favorable functional outcomes was 34.7% in dMT vs. 43.6% among those who received CT (p = 0.307), by day 90 this ratio changed to 40.8% vs. 46.3% (p = 0.542). Mortality rates at day 30 were 22.2% and 23.6% (p = 0.851), and at day 90 33.8% and 25.9% (p = 0.343). The rate of effective recanalization was 94.2% for dMT-treated patients and 98.0% for CT-treated patients (p = 0.318). Symptomatic intracranial hemorrhage was detected in 2.5% of dMT-treated patients and 3.4% of CT-treated group (p = 0.757). CONCLUSION: Our results suggest that CT is associated with a moderately better outcome compared to dMT. IVT prior to MT did not increase the risk of symptomatic intracranial hemorrhages.

Low test-retest reliability of the Epworth Sleepiness Scale within a substantial short time frame.

The Epworth Sleepiness Scale (ESS) is a widely used, validated questionnaire for effectively examining patients' sleepiness in a range of different situations. Test-retest reliability is an important aspect of a questionnaire, which, according to only a few studies, was found to be low in the case of the ESS. All these studies applied long intervals between the tests, thereby increasing the possibility of fundamental change in circumstances, which in turn affect the reliability of the test. The aim of the present study was to investigate the test-retest reliability of the ESS in a short time frame to provide stability of the test circumstances. We also compared the originally used and current accepted statistical methods of test-retest evaluation. We examined 100 unselected patients consecutively referred to the sleep laboratory with the ESS questionnaire, using a test-retest paradigm with an interval of 1 h between two ESS tests. The Lin's concordance coefficient was found to be low, whereas the Pearson's correlation revealed good reliability. Our result provides evidence on the poor test-retest reliability of the ESS, despite the examination protocol excluding changes in test circumstances.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

Cost-effectiveness analysis of invasive EEG monitoring in drug-resistant epilepsy.

PURPOSE: Our aim was to determine the cost-effectiveness of two intracranial electroencephalography (iEEG) interventions: 1) stereoelectroencephalography (SEEG) and 2) placement of subdural grid electrodes (SDGs) both followed by resective surgery in patients with drug-resistant, partial-onset epilepsy, compared with medical management (MM) in Hungary from payer's perspective. METHODS: The incremental health gains and costs of iEEG interventions have been determined with a combination of a decision tree and prevalence Markov process model over a 30-year time horizon in a cost-utility analysis (CUA). To address the effect of parameter uncertainty on the incremental cost-effectiveness ratio (ICER), deterministic and probabilistic sensitivity analyses were performed. RESULTS: Our results showed that both SEEG and SDG interventions represent a more expensive but more effective strategy than MM representing the current standard of care. The total discounted cost of SEEG and SDG were € 32,760 and € 25,028 representing € 18,108 and € 10,375 additional cost compared with MM, respectively. However, they provide an additional 3.931 (in SEEG group) and 3.444 quality-adjusted life years (QALYs; in SDG group), correspondingly. Thus, the ICER of SEEG is € 4607 per QALY gain, while the ICER for SDG is € 3013 per QALY gain, compared with MM. At a cost-effectiveness threshold of € 41,058 per QALY in Hungary, both subtypes of iEEG interventions are cost-effective and provide good value for money. SIGNIFICANCE: Because of the high cost of implanting electrodes and monitoring, the invasive EEG for patients with refractory epilepsy is currently not available in the Hungarian national healthcare system. Our study demonstrated that these procedures in Hungary are cost-effective compared with the MM. As a result, the introduction of iEEG interventions to the reimbursement list of the National Health Insurance Fund Administration was initiated.

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.

[Intracranial EEG monitoring methods]. / Intracranialis EEG-monitorozási eljárások.

Resective surgery is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy. Intracranial EEG (iEEG) is necessary if the seizure-onset zone is localized near to an eloquent cortical area, or if the results of presurgical examinations are discordant, or if an extratemporal epilepsy patient is MRI-negative. Nowadays, 3 kinds of electrodes are used: (1) foramen ovale (FO) electrodes; (2) subdural strip or grid electrodes (SDG); (3) deep electrodes (stereo-electroencephalographia, SEEG). The usage of FO electrode is limited to bitemporal cases. SDG and SEEG have a distinct philosophical approach, different advantages and disadvantages. SDG is appropriate for localizing seizure-onset zones on hemispherial or interhemispherial surfaces; it is preferable if the seizure-onset zone is near to an eloquent cortical area. SEEG is excellent in exploration of deeper cortical structures (depths of cortical sulci, amygdala, hippocampus), although a very precise planning is required because of the low spatial sampling. The chance for seizure-freedom is relatively high performing both methods (SDG: 55%, SEEG: 64%), beside a tolerable rate of complications.

Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke.

BACKGROUND: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored. METHODS: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome. RESULTS: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4% and a specificity of 77.3% (area under the curve: .851, 95% confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value. CONCLUSIONS: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.

[The applicability of 123I-FP-CIT SPECT dopamine transporter imaging in clinical practice]. / A 123I-FP-CIT SPECT dopamin transzporter képalkotás jelentosége a klinikai gyakorlatban.

The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer's disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.

[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.

Are the MDS-UPDRS-Based Composite Scores Clinically Applicable?

BACKGROUND: The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. OBJECTIVES: To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. METHODS: Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. RESULTS: Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. CONCLUSIONS: Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society.

Minimal clinically important differences for the experiences of daily living parts of movement disorder society-sponsored unified Parkinson's disease rating scale.

BACKGROUND: The minimal clinically important difference is the smallest change of scores clinically meaningful to patients. OBJECTIVES: We aimed to calculate these threshold values in association with the International Parkinson and Movement Disorder Society UPDRS (MDS-UPDRS) Parts I and II and to evaluate the feasibility of the composite score of Part I and II (MDS-UPDRS I+II) as an outcome. METHODS: Nine hundred eighty-five paired investigations of 365 patients were reviewed, implementing three different techniques simultaneously. RESULTS: Based on the ordinal regression modeling, the MDS-UPDRS I+II score is an applicable outcome measure. Any improvement greater than 2.64 points or any worsening more than 2.45 points on MDS-UPDRS Part I represent a minimal, yet clinically meaningful change. In reference to Part II, the smallest changes considered clinically relevant were 3.05 and 2.51 points for improvement and deterioration, respectively. The thresholds for MDS-UPDRS I+II were 5.73 points for improvement and 4.70 points for worsening. CONCLUSIONS: Our minimal clinically important difference thresholds can be utilized in clinical practice in judging clinical relevance. © 2016 International Parkinson and Movement Disorder Society.

Changes in Quality of Life in Parkinson's Disease: How Large Must They Be to Be Relevant?

BACKGROUND: Minimal clinically important difference (MCID) is the smallest change in an outcome, which a patient identifies as meaningful. Although the 2 most frequently applied Parkinson's disease (PD) "quality of life" questionnaires (the PDQ-39 and PDQ-8) provide encouragingly similar results, their MCID thresholds appear to be vastly different. Our aim was to calculate the MCID estimates for both PDQ-39 and PDQ-8 Summary Indices (PDQ-39-SI and PDQ-8-SI) by the utilization of both anchor- and distribution-based techniques. METHODS: Nine hundred eighty-five paired investigations of 365 patients were included. Three different techniques were used simultaneously to calculate the MCID values. RESULTS: First, we replicated the previously published results demonstrating how both PDQ-39-SI and PDQ-8-SI provide similar values and respond in a similar way to changes. Subsequently, we calculated the MCID thresholds. The most optimal estimates for MCID thresholds for PDQ-39-SI were -4.72 and +4.22 for detecting minimal clinically important improvement and worsening. For PDQ-8-SI, these estimates were -5.94 and +4.91 points for detecting minimal clinically important improvement and worsening respectively. CONCLUSIONS: Our study is the first one that directly compared the MCID estimates for both PDQ-39-SI and PDQ-8-SI on a large pool of patients including all disease severity stages. These MICD estimates varied across PD severity.

Ictal asystole: A systematic review.

OBJECTIVE: To comprehensively analyze ictal asystole (IA) on a large number of subjects. METHODS: We performed a systematic review of case report studies of patients diagnosed with IA (1983-2016). Each included case was characterized with respect to patient history, IA seizure characteristics, diagnostic workup, and therapy. In addition, comparative analyses were also carried out: two alignments were developed based on the delay between epilepsy onset and IA onset ("new-onset" if <1 year, "late-onset" if ≥1 year) and asystole duration (asystole was "very prolonged" if lasted >30 s). RESULTS: One hundred fifty-seven cases were included. All patients had focal epilepsy. In 7% of cases IA developed during a secondary generalized tonic-clonic seizure. Both the seizure-onset zone and the focal seizure activity at asystole beginning were usually temporal (p < 0.001 and p = 0.001, respectively) and were lateralized to the left hemisphere in 62% (p = 0.005 and p = 0.05, respectively). Asystole duration was 18 ± 14 s (mean±SD) (range 3-96 s); 73% of patients had late-onset, 27% had new-onset IA. Compared to late-onset IA, new-onset IA was associated with female gender (p = 0.023), preexisting heart condition (p = 0.014), focal seizure activity at asystole beginning (p = 0.012), normal neuroimaging (p = 0.013), normal interictal EEG (p < 0.001), auditory aura (p = 0.012), and drug-responsive epilepsy (p < 0.001). "Very prolonged" asystole was associated with secondary generalized tonic-clonic seizures (p = 0.003) and tended to occur in extratemporal lobe seizures (p = 0.074). No IA-related death was reported. SIGNIFICANCE: Characteristics considered to be typical of IA (focal, left temporal seizures appearing on grounds of a long-lasting, intractable epilepsy) seem only partially legitimate. We suggest that in new-onset IA, female gender and a preexisting heart condition could serve as predispositions in an otherwise benign epilepsy. We speculate that in late-onset IA, male-predominant changes in neuronal networks in chronic, intractable epilepsy and an accompanying autonomic dysregulation serve as facilitating factors.