The Latest Articles on Neurodegenerative Movement Disorders

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Neurodegenerative Movement Disorders.

Title: Do cerebrovascular risk factors impact the clinical expression of idiopathic isolated adult-onset dystonia?
Authors: Marcello Mario Mascia, Daniele Belvisi, Marcello Esposito, Roberta Pellicciari, Assunta Trinchillo, Carmen Terranova, Salvatore Bertino, Laura Avanzino, Francesca Di Biasio, Francesco Bono, Vincenzo Laterza, Christian Lettieri, Roberto Eleopra, Giovanni Fabbrini, Pierangelo Barbero, Laura Bertolasi, Maria Concetta Altavista, Roberto Erro, Roberto Ceravolo, Anna Castagna, Maurizio Zibetti, Anna Rita Bentivoglio, Giovanni Cossu, Luca Magistrelli, Cesa Scaglione, Alberto Albanese, Maria Sofia Cotelli, Salvatore Misceo, Antonio Pisani, Tommaso Schirinzi, Luca Maderna, Giovanna Squintani, Alfredo Berardelli, Giovanni Defazio, Italian Dystonia Registry Participants, Claudio Zaccone, Denise Cerne, Giovanni Idone, Gina Ferrazzano, Sara Rinaldo, Kais Humaidan, Grazia Devigili, Luigi Polidori, Sonia Mazzucchi, Marina Ramella, Claudia Ledda, Martina Petracca, Valentina Oppo, Elena Contaldi, Marinella Turla, Angelo Fabio Gigante, Francesca Valentino, Daniela Cassano, Nicola Modugno, Nicola Tambasco, Marco Aguggia, Marcello Romano, Lucio Marinelli
Type: Research Article
Abstract:

Backgrounde
Although acquired dystonia may develop following ischaemic/haemorrhagic stroke, the relationship between cerebrovascular disease and idiopathic dystonia has been poorly investigated. This cross sectional study aimed at evaluating the impact of cerebrovascular risk factors on the clinical expression of idiopathic adult onset dystonia (IAOD), with reference to dystonia localization and dystonia-associated features.

Methods
Data were obtained from the Italian Dystonia Registry. Patients with IAOD were stratified into two groups according to the presence of diabetes mellitus and/or arterial hypertension and/or dyslipidemia and/or heart disease. The two groups were compared for demographic features, dystonia phenotype, and dystonia-associated features (sensory trick, tremor, eye symptoms in blepharospasm, and neck pain in cervical dystonia).

Results
A total of 1108 patients participated into the study. Patients who reported one cerebrovascular factor or more (n = 555) had higher age and longer disease duration than patients who did not. On multivariable logistic regression analysis, blepharospasm was the only localization, and sensory trick was the only dystonia-associated feature that was significantly associated with cerebrovascular risk factors. Linear regression analysis showed that the strength of the association between cerebrovascular factors and blepharospasm/sensory trick increased with increasing the number of cerebrovascular factors per patient.

Conclusions
Results of the present study showed that cerebrovascular risk factors may be associated with specific features of IAOD that is development of blepharospasm and sensory trick. Further studies are needed to better understand the meaning and the mechanisms underlying this association.
Access this article: https://doi.org/10.1016/j.parkreldis.2023.105851

Title: MRgFUS of the nucleus ventralis intermedius in essential tremor modulates functional connectivity within the classical tremor network and beyond
Authors: Christine Kindler, Neeraj Upadhyay, Veronika Purrer, Frederic Carsten Schmeel, Valeri Borger, Lukas Scheef, Ullrich Wüllner, Henning Boecker
Type: Research Article
Abstract:

Backgrounde
Magnetic resonance-guided focused ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus is an incisionless lesional treatment for essential tremor.

Objective
To examine relationships between tremor severity and functional connectivity in patients with essential tremor and to assess long-term changes in the tremor network after sonication of the ventral intermediate nucleus.

Methods
Twenty-one patients with essential tremor (70.33 ± 11.32 years) were included in the final analysis and underwent resting state functional magnetic resonance imaging at 3 T before and 6 months after treatment. Tremor severity (Fahn-Tolosa-Marin Clinical Rating Scale) was evaluated and functional connectivity was investigated using independent component analysis.

Results
MRgFUS of the thalamic ventral intermediate nucleus reduced contralateral tremor effectively. Multiple regression analysis revealed exclusively negative correlations between FC and tremor severity, notably in the right cerebellar lobe VI and the left cerebellar lobe VIIIa (cerebellar network), in the left occipital fusiform gyrus (lateral visual network), the anterior division of the left superior temporal gyrus (fronto-parieto-temporal network), and in the posterior division of the left parahippocampal gyrus and the bilateral lingual gyri (default mode network). Six months after treatment, increased functional connectivity was observed in almost all tremor-associated clusters, except the cluster localized in the left cerebellum.

Conclusions
Our findings suggest that tremor-related activity in essential tremor extends beyond the classical cerebellar network, additionally involving areas related to visual processing. Functional restoration of network activity after sonication of the ventral intermediate nucleus is observed within the classical tremor network (cerebellum) and notably also in visual processing areas.
Access this article: https://doi.org/10.1016/j.parkreldis.2023.105845

Title: Restless legs syndrome: From clinic to personalized medicine
Authors: S. Chenini, L. Barateau, Y. Dauvilliers
Type: Review

Abstract:

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder that impairs sleep, mood and quality of life. RLS is defined by an urge to move the legs at rest that increases in the evening and at night, and is frequently associated with metabolic and cardiovascular diseases. Symptoms frequency, age at RLS onset, severity, familial history and consequences of RLS vary widely between patients. A genetic susceptibility, iron deficiency, dopamine deregulation, and possible hypo-adenosinergic state may play a role in the pathophysiology of RLS. Polysomnographic recordings found often periodic leg movements during sleep and wakefulness in patients with RLS. RLS can be classified as primary or comorbid with major diseases: iron deficiency, renal, neurological, rheumatological and lung diseases. First-line treatments are low-dose dopamine agonists, and alpha-2-delta ligands depending on the clinical context, and second/third line opiates for pharmacoresistant forms of RLS. Augmentation syndrome is a serious complication of dopamine agonists and should be prevented by using the recommended low dose. Despite an increase in knowledge, RLS is still underdiagnosed, poorly recognized, resulting in substantial individual health burden and socioeconomic coast, and education is urgently needed to increase awareness of this disabling disorder.

Title: Simplified muscle-recruitment strategy during walking in Parkinson's disease people: a time-frequency analysis of EMG signal
Authors: Francesco Di Nardo, Marco Romanato, Fabiola Spolaor, Daniele Volpe, Sandro Fioretti, Zimi Sawacha
Type: Original Article

Abstract:

Objective
Although gait analysis has been widely adopted to describe Parkinson's disease (PD) dysfunctions during walking, few efforts have been made to understand muscle activity role. The current study aims to characterize lower-limb-muscle recruitment during walking in time-frequency domain, based on Continuous Wavelet Transform (CWT) analysis of surface-electromyography (sEMG) signal from lower-limb muscles.

Materials and methods
sEMG signals from Tibialis Anterior (TA), Gastrocnemius Lateralis (GL), Rectus Femoris (RF), and Biceps Femoris (BF) of 20 people with PD and 10 age-matched healthy controls (HC) were acquired during gait. sEMG signals were processed applying a CWT-based approach to assess the occurrence frequency (OF, i.e., the percentage of strides of each muscle activation occurrence) and the frequency content of each muscle activation (in Hz). These parameters are rarely quantified in PD.

Results
Compared to HC, people with PD displayed a significant decrease (p<0.05) in="" median="" of="" on="" and="" indicating="" a="" tendency="" to="" reduce="" the="" global="" involvement="" lower-limb="" muscles.="" no="" significant="" differences="" p="">0.05) in OF were detected among muscle within the same population. No significant changes (p>0.05) in frequency content were revealed in PD.

Conclusions
This analysis suggests that people with PD are characterized by a reduced recruitment of those muscles typically adopted to finely control body-segment motion and a concomitant increased recruitment of those muscles mainly involved in locomotion. No substantial alteration in recruiting muscle fibers is associated with PD. These findings suggests that people with PD are inclined to adopt simpler muscular-recruitment strategies during walking, compared to HC.

Access this article: https://doi.org/10.1016/j.irbm.2023.100798

Title: Utilizing speech analysis to differentiate progressive supranuclear palsy from Parkinson's disease
Authors: Kyurim Kang, Adonay S. Nunes, Mansi Sharma, A.J. Hall, Ram Kinker Mishra, Jose Casado, Rylee Cole, Marc Derhammer, Gregory Barchard, Bijan Najafi, Ashkan Vaziri, Anne-Marie Wills, Alexander Pantelyat
Type: Short communication

Abstract:

Introduction
Distinguishing Parkinson's disease (PD) from Progressive supranuclear palsy (PSP) at early disease stages is important for clinical trial enrollment and clinical care/prognostication.

Methods
We recruited 21 participants with PSP(n = 11) or PD(n = 10) with reliable caregivers. Standardized passage reading, counting, and sustained phonation were recorded on the BioDigit Home tablet (BioSensics LLC, Newton, MA USA), and speech features from the assessments were analyzed using the BioDigit Speech platform (BioSensics LLC, Newton, MA USA). An independent t-test was performed to compare each speech feature between PSP and PD participants. We also performed Spearman's correlations to evaluate associations between speech measures and clinical scores (e.g., PSP rating scales and MoCA). In addition, the model's performance in classifying PSP and PD was evaluated using Rainbow passage reading analysis.

Results
During Rainbow passage reading, PSP participants had a significantly slower articulation rate (2.45(0.49) vs 3.60(0.47) words/minute), lower speech-to-pause ratio (2.33(1.08) vs 3.67(1.18)), intelligibility dynamic time warping (DTW, 0.26(0.19) vs 0.53(0.26)), and similarity DTW (0.43(0.27) vs 0.67(0.13)) compared to PD participants. PSP participants also had longer pause times (17.24(5.47) vs 8.45(3.13) sec) and longer total signal times (52.44(6.67) vs (36.67(6.73) sec) when reading the passage. In terms of the phonation ‘a’, PSP participants showed a significant higher spectral entropy, spectral centroid, and spectral spread compared to PD participants and no differences were found for phonation ‘e’. PD participants had more accurate reverse number counts than PSP participants (14.89(3.86) vs 7.36(4.67)). PSP Rating Scale (PSPRS) dysarthria (r = 0.79, p = 0.004) and bulbar item scores (r = 0.803, p = 0.005) were positively correlated with articulation rate in reverse number counts. Correct reverse number counts were positively correlated with total Montreal Cognitive Assessment scores (r = 0.703, p = 0.016). Machine learning models using passage reading-derived measures obtained an AUC of 0.93, and the sensitivity/specificity in correctly classifying PSP and PD participants were 0.95 and 0.90, respectively.

Conclusion
Our study demonstrates the feasibility of differentiating PSP from PD using a digital health technology platform. Further multi-center studies are needed to expand and validate our initial findings.

Access this article: https://doi.org/10.1016/j.parkreldis.2023.105835