Cardiometabolic factors may influence migraine biology through metabolic, inflammatory, and vascular mechanisms, but studies examining insulin resistance and dyslipidaemia in migraine have yielded inconsistent results, partly due to heterogeneity in study design, fasting status, and timing of blood sampling relative to migraine attacks. We evaluated insulin-resistance indices and lipid profiles, including derived lipid ratios, in episodic migraine compared with healthy controls under standardised interictal fasting conditions. In this cross-sectional case-control study, 45 adults with episodic migraine and 45 healthy controls aged 18–50 years underwent 12-hour fasting blood sampling during the interictal period. Co-primary endpoints were homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C ratio), and atherogenic index of plasma (AIP). Multivariable linear regression models were adjusted for age, sex, body mass index, and smoking. After adjustment for age, sex, BMI, and smoking, episodic migraine remained associated with a higher TC/HDL-C ratio (B = 0.956, p < 0.001), higher AIP (B = 0.122, p = 0.008), higher total cholesterol, LDL-C, non-HDL-C, and fasting glucose, and lower HDL-C, whereas no adjusted association was found for HOMA-IR or fasting insulin. In unadjusted analyses, triglycerides were also higher in the migraine group. Monthly migraine days and attack intensity were not associated with the co-primary metabolic indices. Exploratory subgroup analyses showed nominal lipid-related differences by aura status, which did not remain significant after false discovery rate correction. Under standardised interictal fasting conditions, episodic migraine was associated with a more atherogenic lipid profile, including higher TC/HDL-C ratio and AIP. In contrast, fasting surrogate markers of insulin resistance were not associated with episodic migraine after adjustment for selected covariates, although small effects cannot be excluded. Larger longitudinal studies with more detailed metabolic assessment are needed to confirm these findings.

Although Parkinson’s disease (PD) is primarily defined by motor symptoms, non-motor manifestations—including deficits in social cognition—are increasingly recognized for their impact on daily functioning. Emotion recognition impairment is one such deficit, but prior research has mainly focused on facial expressions, neglecting other socially relevant cues such as body postures. This study examined recognition of emotions from both faces and bodies and their cognitive and neuroanatomical correlates in non-demented patients with PD. We enrolled 25 individuals with mild to moderate PD and 24 age-matched healthy controls. Emotion recognition was assessed with validated facial (ER-40) and bodily (BR-40) tasks. Cognitive function was evaluated with the Montreal Cognitive Assessment, Dementia Rating Scale-2 and Frontal Assessment Battery. Motor symptoms were rated using the MDS-UPDRS Part III. Structural MRI data were analyzed with FreeSurfer. Compared with controls, patients with PD showed a specific impairment in recognizing emotions from body postures, despite comparable overall performance to controls. Within the PD group, poorer recognition was associated with greater cognitive impairment and higher bradykinesia subscores. MRI volumetry linked emotion recognition performance to the volumes of the cerebellar white matter, hippocampus, and left nucleus accumbens. In addition to these structures, facial emotion recognition was specifically related to cerebellar cortical volume, whereas body posture recognition showed associations with the rightputamen, and right amygdala. These findings highlight modality-specific social cognitive deficits in PD, related to both cognition and structural brain changes.

IntroductionSubclinical impulsive-compulsive behaviors (s-ICBs) in Parkinson's disease (PD) are common, clinically relevant, and frequently underdiagnosed. Objective behavioral measures reflecting vulnerability to impulsive-compulsive behavior are lacking. We investigated whether oculomotor measures of inhibitory control are associated with s-ICBs in dopaminergically treated PD patients without clinically manifest impulse control disorders.MethodsTwenty-nine patients with PD (Hoehn and Yahr stages 1-2) and twenty age-matched healthy controls completed prosaccade and antisaccade eye-tracking tasks. Executive functioning, trait impulsivity, quality of life and s-ICBs were assessed. Group comparisons and association analyses were performed using nonparametric methods with false discovery rate correction. Exploratory mediation analysis examined relationships between levodopa equivalent daily dose (LEDD), s-ICBs severity, and express prosaccades. All assessments were performed in the ON-medication state.ResultsCompared with healthy controls, patients with PD showed a higher frequency of express prosaccades and prolonged antisaccade latencies. Within the PD group, express prosaccades were moderately to strongly associated with s-ICBs severity and LEDD and were also related to reduced quality of life. Mediation analysis revealed a significant statistical indirect effect of dopaminergic medication on express prosaccades through s-ICBs severity, indicating that behavioral symptoms statistically accounted for a substantial proportion of this association.ConclusionsThese findings demonstrate a close relationship between oculomotor control, subclinical impulsive-compulsive behaviors, and dopaminergic treatment in PD. The results highlight the complexity of non-motor manifestations in PD and underscore the need for longitudinal and mechanistic studies to clarify their clinical significance.

IntroductionAbout half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. Although up to 40% of adults with mild TBI experience persistent functional deficits, there is no proven-effective treatment to facilitate recovery after it.Methods and analysisThis randomized placebo-controlled multi-centre study was aimed to examine the efficacy of herbal supplement MLC901 on complex attention following mild TBI at 6 months post-randomisation, as a primary outcome measured by CNS Vital signs (CNS-VS). Adults aged 18-65 years, who were 1-12-months post-mild TBI and experienced cognitive impairment, were randomly assigned to receive either MLC901 two capsules (0.4g/capsule) or placebo three times a day for 6 months using centralized stratified permuted block randomization. Secondary outcomes: Rivermead Post-Concussion Symptoms Questionnaire (RPQ; neurobehavioral sequelae); Health Related Quality of Life (QOLIBRI); Hospital Anxiety and Depression Scale (HADS); and safety. Mixed effects models of repeated measures with intention to treat analysis were employed. A Least Square Mean Difference (LSMD) from baseline to 3-, 6-, and 9-month follow-up was calculated with 95% confidence intervals (CI).ResultsIn the analysis, 182 participants (47.8% females) were included. Multivariable mixed effects model analysis did not reveal significant improvements in complex attention (LSMD = -1.18 [95% CI -5.40; 3.03; p = 0.58]) and other cognitive domains at 6 months in the MLC901 group compared to the Placebo group. There were significant improvements in RPQ, QOLIBRI, anxiety and depression in the MLC901 group compared to the Placebo group at 6 and 9 months (LSMD -4.36 [-6.46; -2.26] and -4.07 [-6.22; -1.92], 4.84 [1.58; 8.10] and 3.74 [0.44; 7.03], -1.50 [-2.29; -0.71 and -0.96 [-1.84; -0.08], -1.14 [-1.92; -0.35] and -1.14 [-1.94; -0.34]), respectively. MLC901 tested was proven safe.ConclusionsAlthough the 6-month treatment with MLC901 did not result in a statistically significant difference with placebo for CNS-VS measurement of cognitive domains in individuals with mild TBI, the study showed a clinically and statistically significant improvement in all clinical scales assessed by the investigators.Trial registrationClinicalTrials.gov identifier NCT04861688.

IntroductionParkinson’s disease (PD) is a progressive neurodegenerative disorder, in advanced stages characterized by motor and non-motor fluctuations, significantly impacting patients’ quality of life (QoL). Advanced therapies, such as levodopa/carbidopa intestinal gel or carbidopa/levodopa enteral suspension (LCIG/CLES) and levodopa/entacapone/carbidopa intestinal gel (LECIG), offer continuous levodopa administration to reduce fluctuations and improve QoL. However, these therapies require invasive percutaneous endoscopic gastrostomy with jejunal extension (PEG-J), which can lead to complications. This study aimed to analyze the incidence of complications related to gastrojejunostomy in patients treated with LCIG/CLES or LECIG and their impact on therapy outcomes.MethodsThis retrospective study included PD patients treated with LCIG/CLES or LECIG at our center over 15 years. Patients were included if they had a PEG-J inserted and had been on LCIG/CLES or LECIG for at least 3 months. Complications were analyzed to identify trends and practical solutions for management.ResultsOf 111 PEG-J insertions, we analyzed 106 patients treated with LCIG/CLES or LECIG. A total of 77.4% experienced at least one adverse event (AE), predominantly device-related (69.8%). Common complications included knotting (24.4%), disconnection (22.8%), and occlusion (17.1%) of the inner tube. Serious AEs were rare but included three deaths within 30 days post-procedure, severe skin phlegmon in two patients, and severe gastrointestinal discomfort in one patient. The duration of PEG-J significantly correlated with AEs.ConclusionGastrojejunostomy-related AEs in LCIG/CLES and LECIG therapies are common but generally manageable with proper intervention. Serious complications are rare, with less than 10% discontinuing treatment due to dissatisfaction.

Neuroinflammation plays a critical role in the pathophysiology of multiple sclerosis (MS), involving complex interactions between reactive oxygen species (ROS), cytokines, chemokines, and immune cells. Among these, neutrophils contribute to sustained inflammation through degranulation, ROS production, and the release of neutrophil extracellular traps (NETs). Extracellular DNA (ecDNA), a key component of NETs, may act as an autoantigen, promoting chronic inflammation and tissue damage. Additionally, impaired NETs and ecDNA degradation by deoxyribonucleases (DNases) may contribute to persistence of inflammation. The aim of the present study was to determine the levels of ecDNA and DNase activity in both blood plasma and cerebrospinal fluid (CSF) in newly diagnosed, treatment-naïve adult patients with relapsing–remitting MS and whether it correlates with disease severity and inflammatory activity in MS. Fifty-one treatment-naïve relapsing–remitting MS patients without disease-modifying therapy and 16 healthy controls (HC) were included in our study. Blood and CSF samples were analyzed for ecDNA, mitochondrial DNA (mtDNA) levels, and DNase activity. Correlations with inflammatory cytokines, oxidative stress, MRI lesion burden, and the expanded disability status scale (EDSS) were analyzed. MS patients exhibited significantly elevated ecDNA levels and reduced DNase activity in blood plasma compared to HC. EcDNA levels positively correlated with inflammatory cytokines, oxidative stress, and disease severity (EDSS). Furthermore, ecDNA and mtDNA levels in CSF positively correlated with inflammatory gadolinium-enhancing MRI lesions. Interestingly, no DNase activity was detected in CSF in both MS patients and HC. Our findings demonstrate that MS patients exhibit significantly elevated ecDNA levels and reduced DNase activity in blood plasma, which correlate with inflammatory cytokines, oxidative stress, and disease severity (EDSS). Additionally, increased ecDNA and mtDNA levels in CSF are associated with higher inflammatory activity, as reflected by gadolinium-enhancing MRI lesions. Considering the pro-inflammatory nature of ecDNA in perpetuating sterile inflammation, these results suggest a potential role of circulating nucleic acids in MS pathogenesis. Furthermore, impaired DNase activity may contribute to the persistence of ecDNA, potentially sustaining pro-inflammatory state in MS. Nevertheless, it remains unclear whether elevated ecDNA actively contributes to neuroinflammation or simply reflects ongoing immune activation. Further research is needed to elucidate the mechanisms underlying ecDNA release and degradation and its implications in MS progression.

Parkinson's disease (PD) impairs balance and gait, increases fall risk, and reduces quality of life. While levodopa remains the primary treatment, it has limited effects on postural instability. Exercise training offers complementary benefits. This study examined the effects of supervised aerobic-strength exercise on postural stability and gait in PD patients, focusing on differences between ON and OFF medication states and relationships between static balance and dynamic balance during normal and dual-task walking. Fifteen PD patients completed a 4-month exercise training, with pre- and post-intervention assessments in both medication states using trunk accelerometry for static balance assessment during stance with eyes open and closed on firm and foam surfaces; and a markerless camera system for dynamic balance assessment during walking. The MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Berg Balance Scale (BBS) were utilized. Post-intervention, motor MDS-UPDRS scores improved significantly in both ON (p = 0.013) and OFF (p < 0.001) states. BBS scores increased (p = 0.005), and several postural parameters decreased in the OFF state in multiple conditions. During dual-task walking, stance time decreased in both ON (p = 0.048) and OFF (p = 0.026) states, while walking speed increased ON medication (p = 0.018). Trunk sway reduction correlated positively with stance time during dual-task walking. However, correlations between postural and gait changes without dual-task were either absent or inverse. These findings suggest that aerobic-strength exercise enhances postural stability and dual-task gait performance, particularly OFF medication. The distinct correlations between changes in postural and gait parameters indicate that specific tasks uniquely affect motor function outcomes, highlighting the need to fine-tune examination strategies in movement disorder research.

Non-adherence to pharmacotherapy in Parkinson’s disease (PD) is associated with worse clinical outcomes and poor quality of life (QoL). Early identification of non-adherent patients is crucial, as appropriate interventions can improve clinical conditions and QoL. Our study aimed to use cluster analysis to identify risk profiles of patients with lower adherence rates. We included 124 cognitively intact patients with PD. Validated diagnostic instruments were used to measure adherence, QoL, non-motor symptoms (NMS), motor involvement, and complications. K-Means clustering was employed to create empirical subtypes based on these variables. Cluster analysis identified four distinct PD subtypes. Subtype 1 was characterized by worse motor state, frequent NMS, and poor QoL without complications. Subtype 2 had higher LEDD and complications but lower scores in other parameters. Subtype 3 showed low scores across all parameters, indicating a relatively good clinical condition. Subtype 4 showed higher scores in all observed parameters. Adherence levels significantly differed between subtypes (Cramer's V = 0.262, p = 0.009), with subtypes 1 and 4 showing lower adherence and subtype 3 showing higher adherence. Patients with worsened motor state, NMS, and complications are more prone to lower adherence, which correlates with poorer QoL. Early identification and targeted interventions are essential to enhance adherence in these groups.

Physical exercise improves clinical state of patients with Parkinson’s disease (PD), and evidence from experimental models suggests it has a potential to slow down the disease progression. Improved glucose metabolism as well as exerkines, bioactive molecules released into circulation with each exercise bout, contribute to the synchronized exercise-induced adaptive response at a systemic level. Our aim was to assess effects of exercise on clinical state and molecular changes in cerebrospinal fluid (CSF) and blood of patients with PD. Patients with PD (H&Y score I-III, 9F/17M; age 63.3 ± 8.4yrs; BMI 26.5 ± 5.9kg/m 2 ) underwent supervised 4-month aerobic-strength training (3×1h/week). Clinical state (MDS-UPDRS), body composition (BIA/MRI), cognitive functions (CogState, ACE-R, TMT-A&B, DSST, RAVL test), VO 2 max (Rockport 1 mile walk test), muscle strength (dynamometry), resting metabolic rate, metabolic substrate flexibility (indirect calorimetry), and insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed and CSF was sampled by atraumatic lumbar puncture (in a subpopulation) before / after 4-month intervention. Extracellular vesicles (EVs) were isolated from serum and CSF by size exclusion chromatography (SEC). Proteomic analysis (mass spectrometry) of the samples is currently ongoing. Four-month aerobic-strength exercise improved or tended to improve clinical state (MDS-UPDRS, p<0.05), body composition (reduced: BMI, p = 0.007; body fat, p = 0.08; visceral fat, p = 0.038) and cognitive performance (ACE-R verbal production subscore, p = 0.029; psychomotor function, p = 0.04; visual learning & short-term memory, p = 0.009) in patients with PD. Training reduced circulating HbA1C, improved whole-body metabolic flexibility (substrate preference based on the substrate availability, the hallmark of healthy metabolism) and muscle strength (all p<0,05). Proteomic analysis of the samples obtained before and after training is in progress. A relatively short aerobic-strength exercise has favorable effects on cognition and clinical state in patients with PD which could be, at least in part, related to the improvements in patients’ physical fitness and metabolism. It is plausible to speculate that the specific training-induced changes in the proteome of CSF, blood and EVs could be involved in the adaptive response underlying the exercise-induced health benefits in PD. Funding : APVV-20-0466, VEGA-2/0076/22, ADDIT-CE Horizon Europe 101087124

OBJECTIVE:To evaluate the efficacy and safety of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) in patients with focal drug-resistant epilepsy (DRE) using a randomized, single-blinded, crossover design (NCT06681480 on ClinicalTrials.gov). METHODS:Eighteen patients with focal DRE completed two 5-day treatment phases with either active or sham LF rTMS (0.5 Hz, 90 % rMT, 3000 pulses/session), separated by a 3-month washout period. The epileptogenic focus was targeted using MRI-guided neuronavigation. Primary outcomes included monthly seizure frequency, responder and seizure-free rates, and duration of seizure freedom. Secondary outcomes included weekly seizure frequency, interictal epileptiform discharges (IEDs), seizure severity, and quality of life. Crossover-specific analyses were performed with baseline correction. RESULTS:Active rTMS resulted in a significant reduction in monthly seizure frequency compared to sham (p = 0.0399), with 50 % of patients classified as responders and 16.7 % achieving seizure freedom. The seizure reduction was most prominent during the first two weeks after stimulation. Active rTMS also significantly reduced seizure severity (p < 0.0001) and improved quality of life (p = 0.0212). Although a trend toward reduction in IEDs was observed, this did not reach statistical significance. No serious adverse events occurred, and treatment was well tolerated. SIGNIFICANCE:LF rTMS targeting the epileptogenic focus appears to be a safe and potentially effective non-invasive adjunctive therapy for focal DRE. Its short-term efficacy and favorable safety profile support further investigation, including studies incorporating maintenance stimulation protocols and biomarker-guided treatment strategies.

Background and Objectives: Spinal muscular atrophy (SMA) is a progressive, autosomal recessive, rare neuromuscular disorder caused by a genetic defect in the SMN1 gene, where the SMN2 gene cannot sufficiently compensate. Patients experience progressive and predominantly proximal muscular weakness and atrophy. Oculomotor disorders are currently not regarded as a typical feature of SMA. The aim of this study was to determine whether oculomotor abnormalities are present in subjects with SMA and to assess a potential relationship between the oculomotor parameters and disease duration. Materials and Methods: An analysis of 15 patients with SMA type 2 and type 3 and 15 age-matched healthy controls was conducted. The oculomotor performance, including the analysis of smooth pursuit velocity gain and saccades parameters (latency, velocity, accuracy) in the horizontal and vertical directions, was compared between both groups. Results: The analysis of smooth pursuit gain in the participants revealed a marginally significant reduction between the SMA patients and the healthy controls in the horizontal direction at a frequency of 0.2 Hz (p = 0.051), but no significant differences were observed at any other frequency or direction. The vertical velocity of the saccade eye movements of the SMA patients was increased compared with the healthy subjects, which was statistically significant for the amplitude of ±10° (p = 0.030), but not for the amplitude of ±16.5° (p = 0.107). The horizontal saccade latency, saccade velocity and saccade accuracy did not differ significantly between the SMA patients and the controls. None of the oculomotor parameters were associated with disease duration. Conclusions: While certain oculomotor abnormalities, such as increased vertical saccade velocity, were observed in the SMA patients, these findings do not indicate a defining role of oculomotor impairment in SMA pathology or its clinical characteristics.

BACKGROUND:Most of the patients with multiple sclerosis (MS) suffer from cognitive impairment, fatigue and/or mood disturbances. These symptoms are usually resistant to both disease-modifying and symptomatic treatment. Since there is a trend to a holistic approach to MS patients, we aimed to confirm the effect of combined cold exposure, controlled breathing and mindfulness - Wim Hof Method (WHM) - on neuropsychiatric symptoms of MS. METHODS:In this randomized interventional study we examined the change in the score of specific neuropsychiatric scales/questionnaires before and after the 12-week WHM-based training program. We compared the change with a control group with no intervention. RESULTS:We obtained complete data from 12 patients in the WHM group and 13 patients in the control group. After 12 weeks, the WHM group had significantly higher improvement in cognition - SDMT (p = 0.045), TMT-A (p = 0.041), TMT-B (p < 0.001); fatigue - FSMCC (p = 0.039); anxiety - GAD (p = 0.015), and depression - PHQ-9 (p = 0.033). CONCLUSION:Our results indicate that the Wim Hof method appears to be a suitable complementary non-pharmacological treatment for neuropsychiatric symptoms of MS.

BACKGROUND:Leucine-rich repeat kinase 2 (LRRK2) p.L1795F variant was proposed as a genetic risk factor for Parkinson's disease (PD). However, its prevalence, phenotype, and origin remain unknown. OBJECTIVE:The aim was to evaluate the frequency and phenotype of p.L1795F in early-onset PD (EOPD) and familial PD compared to healthy controls (HC) in Central Europe. METHODS:Whole-exome sequencing was used to screen 219 EOPD and familial PD patients of Central Europeans compared to HC. Sanger sequencing assessed segregation. Detailed clinical phenotype was evaluated for all positive carriers. RESULTS:p.L1795F was identified in 1.37% (3/219) and 3.23% of familial cases (3/93), with no carriers among HCs (0/303). Segregation analysis confirmed association with PD. Carriers were traced to the eastern Slovak-Hungarian region. It also appears to be associated with a more aggressive phenotype. CONCLUSION:Our data indicate that p.L1795F contributes to PD in Central Europe. Further exploration in larger cohorts is warranted to establish its contribution to global PD risk.

Background: Headache is a prevalent and disabling non-respiratory symptom of COVID-19, posing a persistent challenge in post-COVID syndrome. This study aimed to determine the prevalence, phenotypes, risk factors and biomarkers associated with COVID-related headaches. Methods: A retrospective analysis of 634 hospitalized COVID-19 patients was conducted, with 295 participants being followed up 12–15 months post-discharge via telephone call. Initial laboratory workups, including complete blood count and various biochemical parameters, were compared between headache and non-headache groups. Results: One-third of hospitalized patients experienced headaches, predominantly younger individuals (p < 0.001) and women (p = 0.002). Non-dominant headaches were characterized as dull (56.9%) and holocranial (26.5%), while dominant headaches were unilateral (31.3%) with photophobia (34.3%) and nausea (56.3%). Persistent headaches were unilateral (40%) and pulsating (38%) with phonophobia (74%). Decreased CD4 T cells independently predicted COVID-associated headaches, with elevated IL-6 levels noted in the dominant-headache group (p = 0.040). Remarkably, 50% of patients reported persistent headaches 12–15 months post-infection. Dexamethasone administration significantly reduced the likelihood of long-COVID headaches (52% vs. 73%, p = 0.029). Conclusions: Headache was present in one-third of patients with heterogenous phenotypes: tension headache in the non-dominant group, and migraine in the dominant and persistent headache groups. Persistent headache remains a challenge, with dexamethasone showing potential in reducing its incidence, emphasizing the need for tailored approaches in managing long-COVID headaches.

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IntroductionBradykinesia is an essential diagnostic criterion for Parkinson’s disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either “pure” dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT).MethodsThe protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings.ResultsThirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group.DiscussionClinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.

AIM OF STUDY:To determine whether a high dose of levodopa-carbidopa intestinal gel (LCIG), expressed as levodopa equivalent daily dose (LE daily dose), is a risk factor for acute polyneuropathy in patients treated with LCIG. CLINICAL RATIONALE FOR STUDY:Treatment with LCIG is an effective device-assisted therapy in the advanced stages of Parkinson's Disease (PD). Polyneuropathy is a well-known complication of PD treatment. Patients treated with oral levodopa usually suffer from sub-clinical or mild chronic sensory polyneuropathy. However, severe acute polyneuropathy occurs in patients treated with LCIG, which is causally related to the treatment and leads to its immediate discontinuation. The etiology is not yet clear, but some patients with acute polyneuropathy have been given high doses of LCIG. MATERIAL AND METHODS:A retrospective multicentre study of patients treated with LCIG was performed. Patients with acute polyneuropathy were subjected to a detailed analysis including statistical processing. RESULTS:Of 183 patients treated with LCIG in seven centres, six patients (five females, median age 63 years) developed acute polyneuropathy with LCIG discontinuation. The median (interquartile range) initial and final LE daily dose in patients with and without acute polyneuropathy was 3,015 (2,695-3,184) and 1,898 (1,484-2,167) mg, respectively. The final LE daily dose of 2,605 mg cut-off had 83% sensitivity and 93% specificity for the prediction of acute polyneuropathy. CONCLUSIONS AND CLINICAL IMPLICATIONS:The risk of acute polyneuropathy in LCIG-treated patients was associated with a daily LE dose of greater than 2,605 mg or with more than a 62% increase in the daily LE dose during LCIG treatment.