The Pathophysiology of Dystonic Tremors and Comparison With Essential Tremor.

There are two types of dystonic tremor syndromes (DTS), dystonic tremor (DT) and tremor associated with dystonia (TAWD), and neither is understood. DTS likely share some mechanisms with nontremulous dystonia, and there may also be overlaps with essential tremor (ET). We studied 21 ET (8 females, 13 males) and 22 DTS human patients (10 females, 12 males), including 13 human patients with DT (writer's cramp with writing tremor) and 9 human patients with tremor associated with dystonia (TAWD; cervical dystonia with hand tremor). Tremors were analyzed using accelerometry and surface EMG of the antagonist pairs of arm muscles during posture, simple kinetic movement, and writing. Cerebellar inhibition was performed to assess cerebello-thalamo-cortical involvement. DT exhibited higher variability of peak frequency and greater instability of tremor burst intervals over time (higher tremor stability index) than ET or TAWD regardless of tasks. Intermuscular coherence magnitude between the antagonist pairs increased during the writing task in DT, but not ET or TAWD. ET and TAWD exhibited different phase relationships of the temporal fluctuations of voluntary movement and tremor in the kinetic condition. A linear discriminant classifier based on these tremor parameters was able to distinguish the three groups with a classification accuracy of 95.1%. Cerebellar inhibition was significantly reduced in DT, but not in TAWD, compared with ET and healthy controls. Our study shows that the two DTS are distinct entities with DT closer to nontremorous dystonia and TAWD closer to ET.SIGNIFICANCE STATEMENT This study provides novel findings about characteristics and pathophysiology of the two different types of dystonic tremor syndromes compared with essential tremor. Patients with DTS are classified into DT who have dystonia and tremor in the same area, and tremor associated with dystonia (TAWD) who have dystonia and tremor elsewhere. Our results showed that DT exhibits increased tremor variability, instability, and intermuscular coherence, and decreased cerebello-thalamo-cortical inhibition compared with TAWD. Our study shows that DT and TAWD are distinct phenotypes, and that the physiological characteristics of DT are more similar to nontremorous dystonia, and TAWD is closer to ET.

The patchy tremor landscape: recent advances in pathophysiology.

PURPOSE OF REVIEW: We focus on new insights in the pathophysiology of Parkinson's disease tremor, essential tremor, tremor in dystonia, and orthostatic tremor. RECENT FINDINGS: Neuroimaging findings suggest that Parkinson's disease resting tremor is associated with dopaminergic dysfunction, serotonergic dysfunction, or both. Not all tremors in Parkinson's disease have the same pathophysiology: postural tremor in Parkinson's disease can be subdivided into pure postural tremor, which involves nondopaminergic mechanisms, and re-emergent tremor, which has a dopaminergic basis. Unlike Parkinson's disease tremor, essential tremor has an electrophysiological signature suggestive of a single (or several tightly coupled) oscillators. Visual feedback increases essential tremor and enhances cerebral activity in the cerebello-thalamo-cortical circuit, supplementary motor area, and parietal cortex. Little is known about dystonic tremor but the available evidence suggests that both the basal ganglia and the cerebellum play a role. Finally, recent work in orthostatic tremor points towards the role of the pontine tegmentum and dysfunctional cerebellar-SMA circuitry. SUMMARY: Many pathological tremors involve the cerebello-thalamo-cortical circuitry, and the clinical and pathophysiological boundaries between tremor disorders are not always clear. Differences between tremor disorders - or even individual patients - may be explained by the specific balance of neurotransmitter degeneration, by distinct circuit dynamics, or by the role of regions interconnected to the cerebello-thalamo-cortical circuit.

Cerebellar brain inhibition in the target and surround muscles during voluntary tonic activation.

Motor surround inhibition is the neural mechanism that selectively favours the contraction of target muscles and inhibits nearby muscles to prevent unwanted movements. This inhibition was previously reported at the onset of a movement, but not during a tonic contraction. Cerebellar brain inhibition (CBI) is reduced in active muscles during tonic activation; however, it has not been studied in the surround muscles. CBI was evaluated in the first dorsal interosseus (FDI) muscle as the target muscle, and the abductor digiti minimi, flexor carpi radialis and extensor carpi radialis muscles as surround muscles, during rest and tonic activation of the FDI muscle in 21 subjects. Cerebellar stimulation was performed under magnetic resonance imaging-guided neuronavigation targeting lobule VIII of the cerebellar hemisphere. Stimulus intensities for cerebellar stimulation were based on the resting motor cortex threshold (RMT) and adjusted for the depth difference between the cerebellar and motor cortices. We used 90-120% of the adjusted RMT as the conditioning stimulus intensity during rest. The intensity that generated the best CBI at rest in the FDI muscle was selected for use during tonic activation. During selective tonic activation of the FDI muscle, CBI was significantly reduced only for the FDI muscle, and not for the surround muscles. Unconditioned motor evoked potential sizes were increased in all muscles during FDI muscle tonic activation as compared with rest, despite background electromyography activity increasing only for the FDI muscle. Our study suggests that the cerebellum may play an important role in selective tonic finger movement by reducing its inhibition in the motor cortex only for the relevant agonist muscle.

Inducing LTD-Like Effect in the Human Motor Cortex with Low Frequency and Very Short Duration Paired Associative Stimulation: An Exploratory Study.

Introduction. Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency of PAS10 ms protocols in human M1. Methods. Six protocols of low frequency PAS10 ms (ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applying PAS10 ms up to 30 minutes. After we found PAS10 ms protocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects. Results. One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes. Conclusion. Low frequency and very short duration of PAS10 ms potentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort.

Nocturnal manifestations of atypical and vascular parkinsonism: how do they differ from Parkinson's disease?

While nocturnal disturbances of Parkinson's disease (PD) are increasingly recognized as being part of a continuum that includes daytime manifestations, there is still little analysis in the medical literature that assesses these complex phenomena in patients with atypical (AP) and vascular parkinsonisms (VP). The objective of our study was to determine the prevalence of these disturbances in patients with AP and VP and to determine the range of nighttime symptoms that occur compared with those in patients with PD. This comparison was done using a semi-structured interview and self-rated questionnaires in 63 AP and VP patients (PSP 24, MSA 24, CBD 5, and VP 10), and 208 PD patients. 61 AP and VP patients (96.8%) and 201 PD patients (96.6%) reported at least one nocturnal symptom with a score of less than 6 on the Modified Parkinson's Disease Sleep Scale (MPDSS). Nocturnal akinesia, as measured on the Nocturnal Akinesia, Dystonia, and Cramp Score, was found to be significantly greater in patients with PSP (p = 0.006), MSA (p = 0.002), and CBD (p = 0.012) than PD patients, but not VP patients (p = 0.428). Like those with PD, patients with AP and VP identified the problem of getting up at night to urinate (MPDSS item 8) as being the most frequent and troublesome nocturnal symptom. MSA and PSP patients reported more frequent (p = 0.001) and troublesome (p < 0.001) urinary incontinence (MPDSS item 9) than PD patients and MSA patients had more severe problems with unexpectedly falling asleep during the day (MPDSS item 15) than PD patients (p = 0.003). In summary, our study determined that nocturnal manifestations are commonly experienced by patients with AP and VP and highlighted specific nocturnal symptoms, which are more prevalent and troublesome in certain AP syndromes. The concept of 24-h control of symptoms should not be limited to only PD and we recommend that all who are involved in the care of AP and VP patients should realize that many nocturnal symptoms are experienced by these patients and a multidisciplinary approach should be utilized to address these problems.

Nocturnal journey of body and mind in Parkinson's disease: the manifestations, risk factors and their relationship to daytime symptoms. Evidence from the NIGHT-PD study.

Nocturnal manifestations of Parkinson's disease (PD) are myriad, have diverse etiologies and include motor, sleep, urinary, and neuropsychiatric symptoms which are often associated with daytime somnolence. While most patients perceive these symptoms as troublesome, the recognition of nocturnal problems related to PD is still low in clinical practice. We conducted a survey using semi-structured interviews and self-rated questionnaires of 215 consecutive patients with PD enrolled in three centers in Thailand to determine the prevalence and risk factors of nocturnal disabilities and their relationship to daytime symptoms. We found that 96.6% of patients reported the presence of nocturnal symptoms as determined by the modified version of Parkinson's Disease Sleep Scale (MPDSS). Our survey indicated that the most frequent and distressing symptom was the interruption of sleep to pass urine (56.7%, 4.4 ± 3.9). The severity of symptoms revealed in the MPDSS increased along with the disease duration (p < 0.05) and Hoehn and Yahr stages (p = 0.01). There were similar to findings of the Nocturnal Akinesia Dystonia and Cramp Score (NADCS) where patients with advanced disease had significantly higher NADCS scores than early/moderate disease (p < 0.001). There was a significant correlation of total MPDSS scores with the total scores of the 9-item Wearing-Off Questionnaire (WOQ-9); (r = -0.43, p < 0.05) [motor (r = -0.35, p < 0.05) and nonmotor subscores (r = -0.43, p < 0.05)]; total nonmotor symptoms (NMS) scores (r = -0.55, p < 0.05); Parkinson's Disease Questionnaire-8 Summary Index (PDQ-8 SI) (r = -0.52, p < 0.05); and the total NADCS (r = -0.35, p < 0.05). Multiple regression analysis identified PDQ-8 SI (ß = -0.27, p = 0.005) as the most significant predictor of nocturnal manifestations of PD, followed by the nonmotor subscore of WOQ (ß = -0.24, p = 0.006), and the NMS item 20 (feeling light-headed, dizzy, or weak when standing from sitting or lying) (ß = -0.22, p = 0.003). Our study found that nocturnal symptoms of PD are very common and we suggest that good clinical practice should include a comprehensive review of nighttime manifestations, particularly for those patients who already experience "wearing-off" symptoms.

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

Self-treatment of freezing of gait in Parkinson's disease patients using silicone pads to apply Thai acupressure to plantar acupoints: A randomised, controlled trial.

Introduction: Freezing of gait (FOG) involves dysfunction of the motor and sensory systems. Peripheral sensory stimuli, including Thai acupressure, can improve proprioceptive function and decrease FOG episodes. Here, we sought to determine the efficacy of acupressure as a self-treatment to alleviate FOG in patients with Parkinson's disease (PD). Methods: We conducted an open-label, controlled trial of 60 PD patients with FOG while medicated, randomised into two groups: an active-treatment group using silicone pads to apply pressure to plantar acupoints on the head of the big toe and the base of the first metatarsal bone on each foot for 6 s using patient body weight while seated, repeated four times for each acupoint bilaterally, and a sham-treatment group using a similar protocol without the silicone pads. The primary outcome was stride length. Secondary outcomes included FOG episodes, FOG duration, percent duration of FOG to total gait time (%FOG), and gait parameters. A baseline-adjusted analysis of covariance was used to compare outcomes between the two groups. Results: Compared with the sham treatment, the active treatment increased stride length, gait velocity, and cadence (all p < 0.001), and decreased FOG episodes and duration (both p < 0.001), %FOG (p = 0.011), and double-support time (p < 0.001). No adverse effects were noted. Conclusions: Acupressure using silicone pads to stimulate plantar acupoints for self-treatment is a noninvasive, simple, safe way to improve gait and alleviate FOG in patients with PD. Clinical Trial Registration: We registered the study prospectively in the Thai Clinical Trial Registry No. TCTR20200317001.

The rise of Parkinson's disease is a global challenge, but efforts to tackle this must begin at a national level: a protocol for national digital screening and "eat, move, sleep" lifestyle interventions to prevent or slow the rise of non-communicable diseases in Thailand.

The rising prevalence of Parkinson's disease (PD) globally presents a significant public health challenge for national healthcare systems, particularly in low-to-middle income countries, such as Thailand, which may have insufficient resources to meet these escalating healthcare needs. There are also many undiagnosed cases of early-stage PD, a period when therapeutic interventions would have the most value and least cost. The traditional "passive" approach, whereby clinicians wait for patients with symptomatic PD to seek treatment, is inadequate. Proactive, early identification of PD will allow timely therapeutic interventions, and digital health technologies can be scaled up in the identification and early diagnosis of cases. The Parkinson's disease risk survey (TCTR20231025005) aims to evaluate a digital population screening platform to identify undiagnosed PD cases in the Thai population. Recognizing the long prodromal phase of PD, the target demographic for screening is people aged ≥ 40 years, approximately 20 years before the usual emergence of motor symptoms. Thailand has a highly rated healthcare system with an established universal healthcare program for citizens, making it ideal for deploying a national screening program using digital technology. Designed by a multidisciplinary group of PD experts, the digital platform comprises a 20-item questionnaire about PD symptoms along with objective tests of eight digital markers: voice vowel, voice sentences, resting and postural tremor, alternate finger tapping, a "pinch-to-size" test, gait and balance, with performance recorded using a mobile application and smartphone's sensors. Machine learning tools use the collected data to identify subjects at risk of developing, or with early signs of, PD. This article describes the selection and validation of questionnaire items and digital markers, with results showing the chosen parameters and data analysis methods to be robust, reliable, and reproducible. This digital platform could serve as a model for similar screening strategies for other non-communicable diseases in Thailand.

The spectrum of preclinical gait disorders in early Parkinson's disease: subclinical gait abnormalities and compensatory mechanisms revealed with dual tasking.

Patients with early Parkinson's disease (PD) may not complain of gait difficulties but subtle gait abnormalities may be revealed as part of a "preclinical gait syndrome" when they are challenged by dual tasks. 21 early PD patients (n = 21, mean age 63.5 years, H&Y 1.62, disease duration <5 years, mean UPDRS-III 7.7) who did not have gait complaints were as compared to age- and gender-matched healthy controls (n = 21). Memory function was not different between the two groups. Under normal walking conditions, there were no significant differences in gait parameters between the patients and the control group. In both groups, normalized gait velocity decreased in response to dual tasking in a parallel fashion (p < 0.001). Similarly, gait variability increased in both groups with dual tasking although not statistically significant. In PD patients, the performance of an additional task resulted in an increased number of cadences (p = 0.04), a reduction in swing time (p = 0.02) and cycle time (p = 0.04) compared with the control group but there was no significant reduction in normalized velocity. Stride width also increased in the PD patients. The addition of a cognitive task may affect certain aspects of gait and is able to elicit subclinical deficits in early PD patients. In an attempt to maintain velocity, early PD patients develop compensatory mechanisms by increasing cadence and decreasing swing time and cycle time. Increased step width helps support balance, and prevents going beyond the base-of-support which may predispose to unsteadiness and falls. We propose that these findings occur as part of a spectrum of a "preclinical gait syndrome" and longitudinal studies are needed to assess the predictive values of these early markers of gait deficits.

Residual effects of combined vibratory and plantar stimulation while seated influences plantar pressure and spatiotemporal gait measures in individuals with Parkinson's disease exhibiting freezing of gait.

Introduction: Combined plantar pressure and vibratory stimulation has been shown to decrease freezing of gait (FOG) episodes and improve spatiotemporal gait parameters compared to single stimulation in Parkinson's disease (PD) patients with FOG. However, the effect of combined plantar stimulations on plantar pressure analysis has never been explored. Methods: Forty PD patients with frequent FOG were allocated to either FOG shoes embedded with a 100 Hz vibratory stimulation at the Achilles tendons and a soft thickened silicone pad at the hallux and sole, or sham shoes with a non-working vibratory motor and a flat non-pressure silicone pad (20 patients per arm) while seated for 96 s. The objective gait and plantar pressure analysis were measured immediately after the stimulation. Outcomes included the normalized percentage of changes in percent FOG (%FOG) and plantar pressure in the heel-strike and push-off phase that were compared between pre- and post-stimulations. Results: The FOG shoes group showed significantly decreased %FOG (81.5 ± 28.9% vs. 6.8 ± 22.1%, p < 0.001), plantar pressure in the heel-strike (47.8 ± 43.7% vs. 4.3 ± 9.8%, p < 0.001), plantar pressure in the push-off (57.7 ± 59.6% vs. 6.2 ± 11.6%, p < 0.001), force time integral (FTI) (40.9 ± 32.5% vs. 6.6 ± 17.3%, p < 0.001), and decreased heel contact time (19.3 ± 12.3% vs. 22.7 ± 32.5%, p < 0.001) when compared to the sham group. There was a strong negative correlation between %FOG and peak plantar pressure (r = -0.440, p = 0.005), plantar pressure in the heel-strike (r = -0.847, p < 0.001). Conclusion: Our study demonstrated that the FOG shoe could decrease FOG episodes by improving the heel-strike pressure, toe push-off and normalized heel-to-toe plantar pressure, suggesting that modification inputs from the peripheral sensory systems might significant improvement in FOG in PD.

Exploring the Complex Phenotypes of Impaired Finger Dexterity in Mild-to-moderate Stage Parkinson's Disease: A Time-Series Analysis.

BACKGROUND: Impaired dexterity is an early motor symptom in Parkinson's disease (PD) that significantly impacts the daily activity of patients; however, what constitutes complex dexterous movements remains controversial. OBJECTIVE: To explore the characteristics of finger dexterity in mild-to-moderate stage PD. METHODS: We quantitatively assessed finger dexterity in 48 mild-to-moderate stage PD patients and 49 age-matched controls using a simple alternating two-finger typing test for 15 seconds. Time-series analyses of various kinematic parameters with machine learning were compared between sides and groups. RESULTS: Both the more and less affected hands of patients with PD had significantly lower typing frequency and slower typing velocity than the non-dominant and the dominant hands of controls (p = 0.019, p = 0.016, p < 0.001, p < 0.001). The slope of the typing velocity decreased with time, indicating a sequence effect in the PD group. A typing duration of 6 seconds was determined sufficient to discriminate PD patients from controls. Typing error, repetition, and repetition rate were significantly higher in the more affected hands of patients with PD than in the non-dominant hand of controls (p < 0.001, p = 0.03, p < 0.001). The error rate was constant, whereas the repetition rate was steep during the initiation of typing. A predictive model of the more affected hand demonstrated an accuracy of 70% in differentiating PD patients from controls. CONCLUSION: Our study demonstrated complex components of impaired finger dexterity in mild-to-moderate stage PD, namely bradykinesia with sequence effects, error, and repetition at the initiation of movement, suggesting that multiple neural networks may be involved in dexterity deficits in PD.

Clinical features, pathophysiology, treatment, and controversies of tremor in dystonia.

Dystonia and tremor frequently co-occur. In some cases, they have shared biological mechanisms, while in others dystonia and tremor are two comorbid conditions. The term "dystonic tremor" is used to describe tremor in those who have dystonia. Two mutually exclusive definitions of "dystonic tremor" were proposed. According to one definition, dystonic tremor is the tremor in the dystonic body part. An alternate definition of dystonic tremor entails irregular and jerky oscillations that have saw tooth appearance with or without overt dystonia. This paper outlines the differences in two definitions of dystonic tremor and identifies their limitations. Given the diverse views defining "dystonic tremor", this paper will use the term "tremor in dystonia". In addition, we will outline different ways to separate the subtypes of tremor in dystonia. Then we will discuss pathophysiological mechanisms derived from the objective measures and single neuron physiology analyses of tremor in dystonia. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.

Vibratory and plantar pressure stimulation: Steps to improve freezing of gait in Parkinson's disease.

INTRODUCTION: Freezing of gait (FOG) is a devastating symptom that develops in patients with advanced Parkinson's disease (PD) and is often unresponsive to pharmacological treatment. Recent research suggests that FOG may result from dysfunctional plantar peripheral sensory systems. The impact of combined plantar pressure and vibratory stimulation over vibratory or pressure alone on FOG remains unexplored. METHODS: PD patients with FOG were randomised into four groups and treated with combined vibratory and pressure stimulation, vibratory stimulation alone, pressure stimulation alone, or controls (no stimulation). Vibratory stimulation targeted both Achilles' tendons. Simultaneous bilateral pressure stimulation was applied to the first hallux, first metatarsal bone, and the sole. The primary outcome included normalized percent changes in percent FOG measured both pre- and immediately post-stimulation. Other outcomes including clinical rating scale, response to questionnaires, number and duration of freezing episodes, and spatiotemporal gait parameters at pre- and freezing episodes were also explored. RESULTS: Sixty PD patients participated in the study. Patients who were treated with combined vibratory and pressure stimulation responded with significant decreases in normalized percent changes of percent FOG (62.75 ± 25.54%, p < 0.001) compared with those treated with vibration alone (11.38 ± 8.29%, p < 0.001), pressure alone (15.15 ± 16.18%, p < 0.001), or controls (8.59 ± 16.85%, p < 0.001). CONCLUSION: Our study demonstrated the benefit of combined vibratory and pressure stimulation on FOG suggesting that this strategy might be developed as a novel treatment modality for PD patients with FOG.

Multimodal imaging of essential tremor and dystonic tremor.

Despite recent advances in tremor and dystonia classification, it remains difficult to discriminate essential tremor from dystonic tremor as they are similar in appearance and no biomarker exists. Further, tremor can appear in the same or a different body part than the dystonia. The aim of the current study was to better understand the differential pathophysiology of these tremors. We designed a cross-sectional case-control study and recruited 16 patients with essential tremor, 16 patients with dystonic tremor, and 17 age-matched healthy volunteers. We used multi-modal imaging combining resting-state functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy. We measured functional connectivity of resting-state fMRI to assess connectivity in the tremor network, fractional anisotropy and mean diffusivity with diffusion tensor imaging, and GABA+, Glutamate/Glutamine, Choline, and N-Acetylaspartate with spectroscopy (adjusted to Creatine). Our results showed reduced functional connectivity of resting-state fMRI between the cerebellum and dentate nucleus bilaterally for the essential tremor group, but not the dystonic tremor group, compared to healthy volunteers. There was higher fractional anisotropy in the middle cerebellar peduncle bilaterally for the dystonic tremor group compared to the essential tremor group as well as for essential tremor group compared to healthy volunteers. There was also higher fractional anisotropy in the red nucleus and corticospinal tract for essential tremor and dystonic tremor groups compared to healthy volunteers. We also showed reduced mean diffusivity in the cerebellum of both essential tremor and dystonic tremor groups compared to healthy volunteers. Finally, we found elevated GABA+/Cr in the cerebellum of the essential tremor and dystonic tremor groups compared to healthy volunteers, but no difference emerged between essential tremor and dystonic tremor groups. We did not find group differences in the other metabolites. Our results indicate cerebellar alterations in essential tremor and dystonic tremor patients compared to healthy volunteers, and further changes in the cerebellum network for the dystonic tremor patients. suggesting that the cerebellum is affected differently in both tremors.

Role of supplementary motor area in cervical dystonia and sensory tricks.

Sensory trick is a characteristic feature of cervical dystonia (CD), where a light touch on the area adjacent to the dystonia temporarily improves symptoms. Clinical benefit from sensory tricks can be observed before tactile contact is made or even by imagination. The supplementary motor area (SMA) may dynamically interact with the sensorimotor network and other brain regions during sensory tricks in patients with CD. In this study, we examined the functional connectivity of the SMA at rest and during sensory trick performance and imagination in CD patients compared to healthy controls using functional magnetic resonance imaging. The functional connectivity between the SMA and left intraparietal sulcus (IPS) region was lower in CD patients at rest and it increased with sensory trick imagination and performance. SMA-right cerebellum connectivity also increased with sensory trick imagination in CD patients, while it decreased in healthy controls. In CD patients, SMA connectivity increased in the brain regions involved in sensorimotor integration during sensory trick performance and imagination. Our study results showed a crucial role of SMA in sensorimotor processing during sensory trick performance and imagination and suggest the IPS as a novel potential therapeutic target for brain modulation.

The clinical and electrophysiological investigation of tremor.

The various forms of tremor are now classified in two axes: clinical characteristics (axis 1) and etiology (axis 2). Electrophysiology is an extension of the clinical exam. Electrophysiologic tests are diagnostic of physiologic tremor, primary orthostatic tremor, and functional tremor, but they are valuable in the clinical characterization of all forms of tremor. Electrophysiology will likely play an increasing role in axis 1 tremor classification because many features of tremor are not reliably assessed by clinical examination alone. In particular, electrophysiology may be needed to distinguish tremor from tremor mimics, assess tremor frequency, assess tremor rhythmicity or regularity, distinguish mechanical-reflex oscillation from central neurogenic oscillation, determine if tremors in different body parts, muscles, or brain regions are strongly correlated, document tremor suppression or entrainment by voluntary movements of contralateral body parts, and document the effects of voluntary movement on rest tremor. In addition, electrophysiologic brain mapping has been crucial in our understanding of tremor pathophysiology. The electrophysiologic methods of tremor analysis are reviewed in the context of physiologic tremor and pathologic tremors, with a focus on clinical characterization and pathophysiology. Electrophysiology is instrumental in elucidating tremor mechanisms, and the pathophysiology of the different forms of tremor is summarized in this review.

Validation of the Thai Version of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale.

OBJECTIVE: This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). METHODS: The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing. RESULTS: The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions. CONCLUSION: The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.

Using machine learning-based analytics of daily activities to identify modifiable risk factors for falling in Parkinson's disease.

BACKGROUND: Although risk factors that lead to falling in Parkinson's disease (PD) have been previously studied, the established predictors are mostly non-modifiable. A novel method for fall risk assessment may provide more insight into preventable high-risk activities to reduce future falls. OBJECTIVES: To explore the prediction of falling in PD patients using a machine learning-based approach. METHOD: 305 PD patients, with or without a history of falls within the past month, were recruited. Data including clinical demographics, medications, and balance confidence, scaled by the 16-item Activities-Specific Balance Confidence Scale (ABC-16), were entered into the supervised machine learning models using XGBoost to explore the prediction of fallers/recurrent fallers in two separate models. RESULTS: 99 (32%) patients were fallers and 58 (19%) were recurrent fallers. The accuracy of the model to predict falls was 72% (p = 0.001). The most important factors were item 7 (sweeping the floor), item 5 (reaching on tiptoes), and item 12 (walking in a crowded mall) in the ABC-16 scale, followed by disease stage and duration. When recurrent falls were analysed, the models had higher accuracy (81%, p = 0.02). The strongest predictors of recurrent falls were item 12, 5, and 10 (walking across parking lot), followed by disease stage and current age. CONCLUSION: Our machine learning-based study demonstrated that predictors of falling combined demographics of PD with environmental factors, including high-risk activities that require cognitive attention and changes in vertical and lateral orientations. This enables physicians to focus on modifiable factors and appropriately implement fall prevention strategies for individual patients.