Welcome to the WCN 2021 Interactive Program
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- Claudia Trenkwalder (Germany)
PROFILING THE BIOCHEMICAL LYSOSOMAL ACTIVITIES IN BLOOD OF PATIENTS WITH MULTIPLE SYSTEM ATROPHY
- Tatiana Usenko (Russian Federation)
Abstract
Background and Aims:
Existed criteria cannot reliably differentiate of multiple system atrophy (MSA)) with other synucleinophaties (Parkinson’s disease (PD), dementia with Lewy bodies (DLB)) due to the unknown molecular mechanism. Last data suggest that lysosomal dysfunction may play a pivotal role in the pathogenesis of synucleinopathies.The objective of the current study was to define a biochemical profile that could distinguish MSA with other synucleinophaties.
Methods:
163 PD patients, 28 patients with PD dementia (PDD), 44 patients DLB patients, 30 MSA patients and 159 controls were enrolled. GLA, GBA, SMPD1 expressions were analyzed by real-time PCR in CD45+ blood cells. Enzyme activities (Alpha-galactosidase (GLA), glucoceresobridase (GCase), acid sphingomyelinase (ASMase)), substrate concentrations (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM)) were measured by LS-MS/MS in blood.
Results:
Increased HexSph concentration was found in DLB, PDD, MSA patients compared to PD and controls (p<0.01) and it was associated with higher risk of DLB, PDD, MSA and earlier age at onset (AAO) of DLB. SMPD1 expression was decreased in MSA compared to PDD patients and controls (p=0.034, p=0.025, respectively). ASMase activity was decreased in DLB, PDD, MSA patients compared to PD patients (p<0.0001, p=0.012, p<0.0001, respectively) and in MSA compared to controls (p<0.0001). ASM activity in DLB, PDD, MSA patients was decreased compared to PD patients (p<0.01). Lower ASMase activity was associated with higher risk of DLB, PDD, MSA and earlier AAO of PD.
Conclusions:
Our data support the role of lysosomal dysfunction in the pathogenesis of synucleinopathies and more pronounced alteration of lysosomal activities, in particularly, alteration of ASMase activities (SMPD1, ASMase, LysoSM) in MSA. The study was supported by RFBR grant №20-015-00116.
STRIATAL DOPAMINE TRANSPORTER IMAGING AND REST TREMOR PATTERN IN EARLY-STAGE TREMULOUS PATIENTS: IMPLICATIONS FOR CLINICAL PRACTICE
- Andrea Quattrone (Italy)
Abstract
Background and Aims:
The differential diagnosis of rest tremor (RT) disorders is challenging, and often requires single photon emission computed tomography with 123I-ioflupane (DaTscan). We investigated the performance of several tremor electrophysiological features in distinguishing RT patients with and without striatal dopaminergic deficit.
Methods:
Two-hundred and five early-stage RT patients were consecutively enrolled. All patients underwent neurological examination, electrophysiological assessment of RT, and DaTscan. The performance of RT electrophysiological features in distinguishing patients with abnormal and normal DaTscan (RT-DaT+ and RT-DaT-, respectively) were analyzed using Receiver Operating Curve. The association between RT features and DaTscan was evaluated by a logistic regression model.
Results:
RT patients with abnormal DaTscan showed higher tremor amplitude and phase values, lower frequency and similar burst duration than RT patients without dopaminergic deficit. The phase was the tremor feature which performed the best (Area Under the Curve, AUC=0.85) in distinguishing RT-DaT+ from RT-DaT- patients. High phase values (>62°, corresponding to alternating pattern) were strongly associated with abnormal Datscan (Odds =9.46) whereas lower phase values (<62°, synchronous pattern) were associated with normal DaTscan (Odds=3.74). One hundred-fifteen/205 patients showed alternating tremor, and 104/115 (90.4%) had abnormal DaTscan, while 90/205patients had synchronous pattern, and 71/90 (78.9%) had normal DATscan.
Conclusions:
The alternating pattern of RT is a powerful, simple and wide available biomarker of striatal dopaminergic deficit in early-stage tremulous patients. The evaluation of tremor pattern could help clinicians distinguish parkinsonian RT associated with dopaminergic deficit from non-parkinsonian RT with intact dopaminergic neurons, and guide decision-making in clinical practice.
ABILITY OF A SET OF TRUNK ACCELERATION-DERIVED GAIT STABILITY INDEXES TO IDENTIFY GAIT UNBALANCE AND RECURRENT FALLERS IN SUBJECTS WITH PARKINSON’S DISEASE.
- Stefano Filippo Castiglia (Italy)
Abstract
Background and Aims:
Gait abnormality is one of the most invalidating features of subjects with Parkinson’s disease (PD) which leads to a high risk of falls, impairs patients’ autonomy and decreases quality of life. The aims of this study were: (i) to assess the ability of 16 gait stability indexes to identify gait instability and recurrent fallers in persons with Parkinson’s Disease (pwPDs) irrespective of age and gait speed and (ii) to investigate their correlation with clinical and kinematic variables.
Methods:
Fifty-five walking trials from subjects with PD and 55 age-and-speed matched healthy subjects (HS) acquired with an inertial sensor system and included in the study. Based on the acceleration patterns provided by the inertial measurement unit, we calculated the harmonic ratios (HR), percent recurrence and percent determinism (RQAdet), coefficient of variation, normalized jerk score and the longest Lyapunov exponent.
Results:
A value ≤ 1.50 at the HR in the antero-posterior direction (HRAP) discriminated between pwPDs subjects at Hoehn & Yahr stage (HY) 3 and HS with a 67% probability, between pwPDS at HY 3 and pwPDs at lower HY stages with a probability of 73% and it identified recurrent fallers with a probability of 77%. HRAP correlated with pelvic obliquity and rotation. RQAdet in the AP direction discriminated between pwPDs and HS with a 67% probability, irrespective of the HY stage and was correlated with stride duration and cadence. 
Conclusions:
HRAP and RQAdet in the AP direction can be used as age- and speed-independent markers of gait instability.
GAIT ANALYSIS IN NORMAL PRESSURE HYDROCEPHALUS: A META-ANALYSIS
- Massimiliano Passaretti (Italy)
Abstract
Background and Aims:
Gait analysis is a useful instrument to assess gait impairment in Normal Pressure Hydrocephalus (NPH) patients. This is the first meta-analysis to summarize quantitative gait data in NPH. Specifically, we investigated which gait parameters are more likely to improve after tap-test (TT) and CSF shunt surgery (CSS), and differentiate responders (R) from non-responders (NR).
Methods:
A literature review was conducted by accessing PubMed. Papers were selected using search criteria of idiopathic NPH with at least one instrumented measure of gait. We defined three time points of gait assessment: baseline (PRE), after TT (POST-TT) and after CSS (POST-CSS). Five gait metrics were consistently reported and taken into account for the meta-analysis: gait velocity, cadence, step length, stride length, and double limb support time (DLS). Findings were categorized as iNPH (total sample), NPH-NC, not classified according to diversion procedures responsiveness, R (TT-R and CSS-R), and NR (TT-NR and CCS-NR). Healthy controls (HC) were included when reported.
Results:
Twenty studies met the inclusion criteria. TT-R patients improve significantly POST-TT and POST-CSS in each meta-analyzable gait metric. NPH-NC improved in gait velocity, stride length and DLS POST-TT, whereas only in gait velocity POST-CSS. Several gait parameters consistently discriminated R from NR and HC.
Conclusions:
This meta-analysis demonstrates gait analysis is a reproducible quantitative instrument to assess gait in NPH, and is useful in selecting responders to shunt placement. Specific parameters seem to delineate the gait pattern of TT-R, providing a critical opportunity to select patients that will respond to CSS.
BOTULINUM TOXIN INJECTION IN LONGISSIMUS AND ILIOCOSTALIS MUSCLES FOR TREATING PISA SYNDROME: SHORT- AND LONG-TERM EFFECT
- Carlo Alberto Artusi (Italy)
Abstract
Background and Aims:
Pisa syndrome (PS), a reversible ³10° lateral trunk flexion, is a frequent complication of Parkinson's disease (PD). Botulinum toxin (BoNT) showed preliminary short-term efficacy in PS. However, the best muscles to target remain unclear. We sought to analyze the efficacy of BoNT in PS targeting specific paraspinal muscles ipsilateral to the trunk flexion side.
Methods:
Ten PD patients with PS (mean angle 18.6±7.3°) were treated with ultrasound- and electromyography-guided BoNT injections in longissimus-thoracis (50U) and iliocostalis-lumborum (50U) at the flexion side (T0). The primary endpoint was the number of patients improving the lateral trunk flexion angle ³5° (responders) 1 month after BoNT (T1). Secondary endpoints were: improvement of PS-associated pain, as per the visual-analog scale (VAS), and residual BoNT effect after 4 months (T2).
Results:
40% of patients were responders at T1; 50% showed minimal/no improvement, and 10% worsened. Trunk flexion improved by 19.4% (3.2±8°) in the entire group, and 48.8% (10.2±1.2°) in the responders' group. VAS scores improved by 53.6% (1.7±1.9). Seven patients received the 4-month follow-up (T2). Four of them showed further flexion improvement when compared to T1, with T2vs.T0 improvement of 19.2%. VAS score worsened, with T2vs.T0 36.7% higher score.
Conclusions:
BoNT might require differential muscle targeting, according to the different patterns of muscle hyperactivity, and may have a long-lasting effect on trunk flexion, but not on the associated back pain. The findings support the hypothesis of PS being related to altered sensorimotor integration and BoNT acting on the interruption of maladaptive proprioceptive feedback.
INTRINSIC BRAIN FUNCTIONAL CONNECTIVITY PREDICTS TREATMENT-RELATED MOTOR COMPLICATIONS IN EARLY PARKINSON’S DISEASE PATIENTS
- Rosa De Micco (Italy)
Abstract
Background and Aims:
Dopamine replacement therapy (DRT) is the most effective treatment for patients with Parkinson’s disease (PD). However, DRT is complicated by the evolution of treatment-related motor complications which may develop progressively over the disease course. Using resting-state functional MRI, we investigated intrinsic brain networks connectivity at baseline in a cohort of drug-naïve PD patients which successively developed treatment-related motor complications over a 4-year follow-up period compared with patients who did not.
Methods:
Baseline 3Tesla MRI images of 88 drug-naïve PD patients and 20 healthy controls (HC) were analyzed. At the 4-year follow-up, 35 patients have developed treatment-related motor complications (PD-Comp) whereas 53 had not (PD-no-Comp). Single-subject and group-level independent component analysis was used to investigate functional connectivity changes within the major resting-state networks at baseline. Additionally, a region-of-interest analysis was performed within the basal ganglia. Sex and age were run as covariates. Regression analysis was used to investigate baseline predictors of motor complications development.
Results:
At baseline, PD-Compl patients showed a preserved sensorimotor connectivity compared to HC. Moreover, an increased connectivity within the default-mode and the frontoparietal networks as well as within the basal ganglia were detected in PD-Compl compared with PD-no-Compl. Functional connectivity changes at baseline showed to be an independent predictor of motor complications after 4 years.
Conclusions:
Our findings demonstrated that specific functional connectivity changes may characterize drug-naïve PD patients more prone to develop treatment-related complications. We hypothesize that these findings may reflect the presence of early differences within the dopaminergic pathways and might predict development of motor complications over time.
3T MAGNETIC RESONANCE-GUIDED FOCUSED ULTRASOUND THALAMOTOMY IN PATIENTS WITH ESSENTIAL TREMOR: THREE-YEAR CLINICAL EXPERIENCE FROM A SINGLE CENTER
- Stefano Tamburin (Italy)
Abstract
Background and Aims:
Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermedius (Vim) nucleus is emerging as a minimally invasive treatment for patients with disabling and medication-refractory essential tremor (ET). We report our preliminary three-year experience on 52 patients with ET treated from January 2018 to December 2020 in a single center.
Methods:
From January 2018 to December 2020, 52 patients (31 men, 21 women, age: 73.5 ± 7.8 years) underwent MRgFUS thalamotomy of the Vim nucleus for disabling and refractory ET (tremor duration: 22.6 ± 12.1 years) with a 3T magnetic resonance scanner at Verona University Hospital.
Results:
At baseline the total Clinical Rating Scale for Tremor (CRST) score was 45.8 ± 15.6, and the Quality of Life in Essential Tremor Questionnaire (QUEST) score was 40.8 ± 13.8. At one-month follow-up, the total CRST score was 12.8 ± 6.3 and the QUEST score was 10.5 ± 4.1. Response persisted in the majority of patients at three-month, six-month, one-year, two-year and three-year follow-up. Side effects related to Vim nucleus thalamotomy included ataxia, speech disorder, ballism, paresthesia, and lower limb hypasthenia and were mild and transitory in most patients.
Conclusions:
Our data confirm that MRgFUS thalamotomy of the Vim nucleus is an effective and safe treatment for disabling and refractory ET and its effects are long-lasting.
IN-DEPTH PHENOTYPING OF MOVEMENT DISORDERS IN WARS2 ENCEPHALOPATHY
- Federica Rachele Danti (Italy)
Abstract
Background and Aims:
Mitochondrial aminoacyl-tRNA synthetases are essential components of the mitochondrial translation machinery recently associated with a wide spectrum of human diseases. Biallelic mutations in WARS2 gene, which encodes mitochondrial tryptophanyl‐tRNA synthetase, result in early onset neurological disorders, including lethal neonatal encephalomyopathy and milder presentations with pyramidal and extra-pyramidal signs. We aim to assess the neurological phenotype of children with WARS2 related disorders with a focus on movement disorders.
Methods:
We collected clinical, biochemical, genetic, and neuroimaging data of 5 genetically confirmed patients with WARS2 encephalopathy (1 already published and 4 newly reported). Movement disorder phenomenology was characterized in-depth through serial video recordings and medical records review.
Results:
Disease presented within the first 2 years of life with a peculiar action, postural and rest low frequency tremor, which was variably accompanied by deterioration of postural control with axial hypotonia, parkinsonism-dystonia, cerebellar, and pyramidal signs. Three out of five patients, all with severe parkinsonism, carried the recurrent c.37T>G (p.Trp13Gly) variant. Dysautonomic features, dysphagia, gastroparesis, psychiatric issues, epilepsy, and spasticity emerged during the disease course. CSF reduction of homovanillic acid, suggesting brain dopamine depletion, was reported in all patients. An initial good response to levodopa vanished within 2-3 years with residual on-off phenomena in the oldest subjects.
Conclusions:
This cohort confirms WARS2 encephalopathy as an important cause of infantile degenerative parkinsonism with secondary dopamine deficiency. Differently from primary monogenic amines disorders, response to levodopa deteriorates over time mimicking the clinical course observed in Parkinson Disease.