Tremor Frequency Research Articles

Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? – Additional clinical and neuroimaging evidence

BackgroundDelayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. ObjectiveHere we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. MethodsWe retrospectively studied operationalized and quantitative analyses of tremor and gait, as well as [18F]fluorodeoxyglucose (FDG) PET of 12 patients affected by therapy escape. All examinations were carried out with activated DBS (ON) and 72 h after deactivation (OFF72h); gait and tremor were also analyzed directly after deactivation (OFF0h). Changes of normalized glucose metabolism between stimulation conditions were assessed using within-subject analysis of variance and statistical parametric mapping. Additionally, a comparison to the [18F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. ResultsOf the immediately accessible parametric tremor data (i.e. ON or OFF0h) only the rebound (i.e. OFF0h) frequency of postural tremor showed possible correlations with signs of ataxia at ON. Regional glucose metabolism was significantly increased bilaterally in the thalamus and dentate nucleus in ON compared to OFF72h. No differences in regional glucose metabolism were found in patients in ON and OFF72h compared with the healthy controls. ConclusionsRebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.

Online Tracking of the Phase Difference Between Neural Drives to Antagonist Muscle Pairs in Essential Tremor Patients.

Transcutaneous electrical stimulation has been applied in tremor suppression applications. Out-of-phase stimulation strategies applied above or below motor threshold result in a significant attenuation of pathological tremor. For stimulation to be properly timed, the varying phase relationship between agonist-antagonist muscle activity during tremor needs to be accurately estimated in real-time. Here we propose an online tremor phase and frequency tracking technique for the customized control of electrical stimulation, based on a phase-locked loop (PLL) system applied to the estimated neural drive to muscles. Surface electromyography signals were recorded from the wrist extensor and flexor muscle groups of 13 essential tremor patients during postural tremor. The EMG signals were pre-processed and decomposed online and offline via the convolution kernel compensation algorithm to discriminate motor unit spike trains. The summation of motor unit spike trains detected for each muscle was bandpass filtered between 3 to 10 Hz to isolate the tremor related components of the neural drive to muscles. The estimated tremorogenic neural drive was used as input to a PLL that tracked the phase differences between the two muscle groups. The online estimated phase difference was compared with the phase calculated offline using a Hilbert Transform as a ground truth. The results showed a rate of agreement of 0.88 ± 0.22 between offline and online EMG decomposition. The PLL tracked the phase difference of tremor signals in real-time with an average correlation of 0.86 ± 0.16 with the ground truth (average error of 6.40° ± 3.49°). Finally, the online decomposition and phase estimation components were integrated with an electrical stimulator and applied in closed-loop on one patient, to representatively demonstrate the working principle of the full tremor suppression system. The results of this study support the feasibility of real-time estimation of the phase of tremorogenic neural drive to muscles, providing a methodology for future tremor-suppression neuroprostheses.

Physiology of Tremor Reduction by Putting the Hands Together in Essential Tremor.

Essential tremor is a common movement disorder, characterized by 4-12 Hz tremor of the hands and arms that can affect many activities of daily living. It has been reported by patients that when performing tasks bimanually their tremor is reduced, but why this happens is unknown. We measured patients' tremors in different conditions when performed with 1 hand and 2 hands to observe if bimanual task performance changes the characteristics of the tremor. A total of 10 patients with essential tremor participated in the study. Electromyographic electrodes were attached bilaterally to the wrist flexor and extensor muscles, and accelerometers were attached to the dorsum of the hands. For each condition, holding a cup, wingbeat, and extending both arms up, data were collected with a single hand and bimanually with the hands touching. When the hands were touching, there was a significant decrease in both accelerometric and electromyographic power at the tremor frequency. In addition, there was a decrease in coherence between accelerometer and electromyography on the same side. There was no change in the tremor frequency. Tremor amplitude does decrease when the hands are together. Together, the characteristics underlying the decrease in tremor amplitude may indicate a decrease in power of the central oscillator driving the tremor, which we speculate is attributed to the differences in unimanual and bimanual motor control. However, given the small sample size, we note that future hypothesis-driven studies with an a priori power analysis will be required to further explore this phenomenon.

Perceptual, Aerodynamic and Acoustic Evaluation of Vocal Characteristics in Subjects With Obesity

Obesity has tripled since 1975 and affects health across many domains. Increasing body mass index increases the risk to the obese subject of many non-communicable diseases. The study evaluated the perceptive, aerodynamic, and acoustic parameters that characterize the voice of the obese population. Eighty adult subjects (40 participants in each obese and control group) aged 18-50 years were enrolled. The perceptual voice analysis was performed using the Consensus Auditory Perceptual Evaluation of Voice. The aerodynamic and acoustic voice analyses were performed using the MIR Spiro lab instrument and Doctor's Speech software. A digital stopwatch was also used to measure maximum phonation time. Statistical analysis revealed a significant difference (P-value <0.05 and t value >2) between two groups on acoustic parameters, specifically Normalized noise energy and fundamental frequency tremor (F0 tremor). Normalized noise energy and fundamental frequency tremor were greater in the obese group. Moreover, maximum phonation time and expiratory reserve volume were significantly reduced in the obese group. Results of the present study showed poor voice quality and reduced expiratory reserve volume in obese individuals. This could be credited to the adverse effects of accrued adipose on the functioning of the laryngeal and respiratory systems. Increasing body mass index escalates the risk to the obese subjects of many non-communicable diseases.

Triaxial Accelerometry Wireless System for Characterization of Parkinsonian Tremor.

Parkinsonian Tremor (PT) is the most common symptom of Parkinson's disease. Its early detection plays an important role in the diagnosis of the disease as it is often mistaken for another type of tremor, called Essential Tremor (ET). Accelerometry analysis has proven to be a trustworthy method for determining the frequency, amplitude, and occurrence of tremor. In addition, the use of portable and wearable sensors has increased due to the rapid growth of Internet of Things (IoT) technology, allowing data to be collected, processed, stored, and transmitted. In this paper, a wearable system consisting of a digital 3-axis accelerometer ADXL345 and micro-controller unit ESP32 was implemented to transmit accelerometry (ACC) signals from each upper limb simultaneously to a Graphical User Interface (GUI), that was developed in Python as an MQTT client, allowing the user to visualize both real-time and offline signals as well as to add markers to indicate events during the acquisition. Furthermore, this GUI is capable of performing an offline analysis consisting of the computing of Power Spectral Density (PSD) using Welch's method and a Spectrogram to visualize a time-frequency distribution of the ACC signals.

S1913 Antibiotic Combination Therapy Improves Symptoms of Parkinson’s Disease in Individuals With Chronic Constipation

Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons with motor symptoms of tremor, rigidity, bradykinesia and postural instability alongside non-motor symptoms such as constipation. Here we explore the effects of a novel antibiotic combination therapy (ACT) comprising Metronidazole, Vancomycin and Rifaximin for the treatment of constipation, which improved symptoms of PD in two cases. Our findings were validated by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to rank the burden of disease ranging from normal=0 to most severe=272. Case description/methods: Case 1 A 69 y/o male presented with PD and severe constipation including straining to initiate a bowel movement and inability to defecate for up to 1wk. Before commencing ACT, preliminary MDS-UPDRS was 38 and symptoms included asymmetric tremor, cogwheel rigidity, bradykinesia and shuffling gait despite treatment with Levodopa and Carbidopa. At 1yr review on ACT, constipation had abated with daily bowel motions not requiring Movicol. The MDS-UPDRS fell to 21 indicating a 45% reduction even with an unchanged PD medication regimen. Strikingly, there was a diminished tremor, milder cog-wheeling tone and minimal impairment of gait. After concluding ACT, the patient slowly regressed in line with the natural progression of disease. Case 2 A 62 y/o female presented with PD and a 10yr history of constipation, passing a bowel motion once every 4d with bloating and flatulence. Before ACT with added Colchicine was commenced, baseline MDS-UPDRS was 37 and symptoms included asymmetric tremor, rigidity, postural instability and decreased arm swing despite treatment with Pramipexole and Rasagiline. At 1yr follow-up on ACT, constipation had resolved with complete emptying daily and no bloating or flatulence. The MDS-UPDRS fell to 26 denoting a 30% reduction whilst the dosage of PD medication remained constant. Noticeably, there was a decreased frequency of tremor, absence of rigidity, improved balance and greater arm swing. Upon cessation of ACT, the patient had a sustained response and gained further success with self-initiated thiamine injections. Discussion: ACT successfully treated constipation and improved neurological symptoms of PD in two cases. Our findings suggest that treatments modulating the gut microbiota may play a role in reducing the severity and progression of PD as well as ameliorating non-motor symptoms such as constipation.Table 1.: Two cases with Parkinson’s Disease and Chronic Constipation who were treated with Antibiotic Combination Therapy PD: Parkinson’s Disease, MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (ranging from normal=0 to most severe=272), w: With, w/o: Without, BNO: Bowels not open, BO: Bowels open, i: One ii: Two, mg: Milligram, qd: Once a day, bd: Twice a day, qid: Four times a day.

Tremor Class Scaling for Parkinson Disease Patients Using an Array X-Band Microwave Doppler-Based Upper Limb Movement Quantizer

Consensus criteria for tremor classification in Parkinson’s disease (PD) patients are clinically important for automatically evaluating the PD rating scale. Wearable sensing tools with direct contact measurements can obtain physiological signals to monitor tremor symptoms. Then, machine learning algorithms (MLAs) can train the frequency-based parameters and motion features to accurately measure PD-related tremors. Noncontact measurement with customized computer information devices can also digitalize the digitized handwritten patterns with the bespoke movements that a hand makes for identifying tremor classes. However, wearable sensors need a set of multiple electrodes to be placed on a patient’s body to acquire biosignals, and the setup does not allow continuous measurement and limits the patient’s motion range. The handwritten patterns of noncontact-based methods need frequency-domain and linearization transformations. In addition, feature extraction methods and MLAs are limited in complex computations and adaptive applications. Hence, in this work, a noncontact measurement with an array X-band microwave (10 GHz) Doppler-based linear quantizer is designed to continuously measure upper limb movements for tremor class scaling. To overcome the complex computations, time-domain parametric features, including zero crossing (ZC), Willison amplitude (WAMP), and waveform length (WL) indexes, are used to extract the physical changes in the oscillation frequencies, amplitudes, and directions of tremor signals for scaling upper limb tremor (ULT) levels. In the experiments involving 10 subjects, the proposed noncontact bioradar sensor could quantify asymmetrical and irregular oscillations with a positive correlation (mean R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> > 0.85) between the three indexes (ZC, WAMP, WL) and various oscillation frequencies. The linear relationship quantizer could predict the ULT levels from 0 Hz to 8 Hz for PD patients (typical tremor frequency: 4–6 Hz). It could also map the three indexes into colored visual representation for computerized visual analysis.

Volcanic tremor of the 2010 Eyjafjallajökull eruption

SUMMARY Volcanic eruptions in Iceland generally start with an increase in tremor levels. These signals do not have clear onset, like many earthquakes. As the character of the tremor signal is variable from one volcano to another, locating the source of the tremor signal may require different techniques for different volcanoes. Continuous volcanic tremor varied considerably during the course of the Eyjafjallajökull summit eruption, 14 April to 22 May 2010, and was clearly associated with changes in eruptive style. The tremor frequencies ranged between 0.5 and 10 Hz, with increased vigour during an effusive and explosive phase, in comparison with purely explosive phases. Higher-frequency tremor bursts early in the eruption were caused by processes at the eruption site. Location of the tremor using a method based on differential phase information extracted from interstation correlograms showed the tremor to be stable near the eruption vent, through time, for signals between 0.5 and 2 Hz. Analyses of power variations of the vertical component of the tremor with distance from the eruption site are consistent with tremor waveform content being dominated by surface waves in the 0.5–2 Hz frequency range. The tremor source depth was argued to be shallow, less than about 1 km. The attenuation quality factor (Q) was found to be on the order of Q = 10–20 for paths in the area around Eyjafjallajökull and Q = 20–50 for paths outside the volcano. The pattern of radiated wave energy from the tremor source varied with time, defining ten different epochs during the eruption. Thus the tremor-source radiation did not remain isotropic, which needs to be considered when locating tremor based on amplitude, that is azimuthally variable source radiation.

Wearable sensor-driven responsive deep brain stimulation for essential tremor

BackgroundDeep brain stimulation (DBS) is an effective surgical therapy for individuals with essential tremor (ET). However, DBS operates continuously, resulting in adverse effects such as postural instability or dysarthria. Continuous DBS (cDBS) also presents important practical issues including limited battery life of the implantable neurostimulator (INS). Collectively, these shortcomings impact optimal therapeutic benefit in ET. ObjectiveThe goal of the study was to establish a physiology-driven responsive DBS (rDBS) system to provide targeted and personalized therapy based on electromyography (EMG) signals. MethodsTen participants with ET underwent rDBS using Nexus-D, a Medtronic telemetry wand that acts as a direct conduit to the INS by modulating stimulation voltage. Two different rDBS paradigms were tested: one driven by one EMG (single-sensor) and another driven by two or more EMGs (multi-sensor). The feature(s) used in the rDBS algorithms was the pow2er in the participant's tremor frequency band derived from the sensors controlling stimulation. Both algorithms were trained on kinetic and postural data collected during DBS off and cDBS states. ResultsUsing established clinical scales and objective measurements of tremor severity, we confirm that both rDBS paradigms deliver equivalent clinical benefit as cDBS. Moreover, both EMG-driven rDBS paradigms delivered less total electrical energy translating to an increase in the battery life of the INS. ConclusionsThe results of this study verify that EMG-driven rDBS provides clinically equivalent tremor suppression compared to cDBS, while delivering less total electrical energy. Controlling stimulation using a dynamic rDBS paradigm can mitigate limitations of traditional cDBS systems.

Considerations Using Harmaline for a Primate Model of Tremor.

Background:While harmaline has been used as a pharmacological model of essential tremor (ET) in rodents and pigs, less is known about the effects of this pharmacological treatment in awake-behaving non-human primates. In this study, we investigated the time-course, amplitude, frequency, and consistency of harmaline tremor in primates.Methods:Three rhesus macaques were administered doses of harmaline ranging from 2–12 mg/kg (i.m.), and tremorous movements were quantified with accelerometers. One subject was also trained to perform a self-paced cued reaching task, with task engagement assessed under harmaline doses ranging from 2–8 mg/kg (i.m.).Results:Whole-body tremors manifested within 30 minutes of threshold-dose administration, and peak oscillatory frequency ranged between 10–14 Hz. However, large differences in tremor intensity and intermittency were observed across individual subjects under similar dosing levels. Additionally, engagement with the reaching task was dependent on harmaline dose, with performance mostly unaffected at 2 mg/kg and with little task-engagement at 8 mg/kg.Discussion:We provide a detailed assessment of factors that may underlie the heterogeneous responses to harmaline, and lay out important caveats towards the applicability of the behaving harmaline-tremoring non-human primate as a preclinical model for ET.HighlightsThe harmaline-primate is revisited for its potential as a preclinical model of tremor. Spontaneous tremor was heterogenous in amplitude across subjects despite similar harmaline doses, action tremors were not consistently observed, and performance on a behavioral task degraded with higher dosages.

Shallow Slow Earthquake Episodes Near the Trench Axis off Costa Rica

AbstractSlow earthquakes are mainly distributed in regions surrounding seismogenic zones along the plate boundaries of subduction zones. In the Central American subduction zone, large regular interplate earthquakes with magnitudes of 7–8 occur repeatedly around the Nicoya Peninsula, in Costa Rica, and a tsunami earthquake occurred off Nicaragua, just north of Costa Rica, in 1992. To clarify the spatial distribution of various slip behaviors at the plate boundary, we detected and located very low frequency earthquakes (VLFEs) around the Nicoya Peninsula using a grid‐search matched‐filter technique with synthetic templates based on a regional three‐dimensional model. VLFEs were active in September 2004 and August 2005, mainly near the trench axis, updip of the seismogenic zone. The distribution of VLFEs overlapped with large slip areas of slow slip events. Low frequency tremor signals were also found in high‐frequency seismogram envelopes within the same time windows as detected VLFEs; thus, we also investigated the energy rates of tremors accompanied by VLFEs. The range of scaled energy, which is the ratio of the seismic energy rate of a tremor to the seismic moment rate of accompanying VLFE and related to the rupture process of seismic phenomena, was 10−9–10−8. The along‐dip separation of shallow slow and large earthquakes and the range of the scaled energy off Costa Rica are similar to those in shallow slow earthquakes in Nankai, which shares a similar thermal structure along the shallow plate boundary.

Seismo-acoustic characterisation of the 2018 Ambae (Manaro Voui) eruption, Vanuatu

A new episode of unrest and phreatic/phreatomagmatic/magmatic eruptions occurred at Ambae volcano, Vanuatu, in 2017–2018. We installed a multi-station seismo-acoustic network consisting of seven 3-component broadband seismic stations and four 3-element (26–62 m maximum inter-element separation) infrasound arrays during the last phase of the 2018 eruption episode, capturing at least six reported major explosions towards the end of the eruption episode. The observed volcanic seismic signals are generally in the passband 0.5–10 Hz during the eruptive activity, but the corresponding acoustic signals have relatively low frequencies (< 1 Hz). Apparent very-long-period (< 0.2 Hz) seismic signals are also observed during the eruptive episode, but we show that they are generated as ground-coupled airwaves and propagate with atmospheric acoustic velocity. We observe strongly coherent infrasound waves at all acoustic arrays during the eruptions. Using waveform similarity of the acoustic signals, we detect previously unreported volcanic explosions at the summit vent region based on constant-celerity reverse-time-migration (RTM) analysis. The detected acoustic bursts are temporally related to shallow seismic volcanic tremor (frequency content of 5–10 Hz), which we characterise using a simplified amplitude ratio method at a seismic station pair with different distances from the vent. The amplitude ratio increased at the onset of large explosions and then decreased, which is interpreted as the seismic source ascent and descent. The ratio change is potentially useful to recognise volcanic unrest using only two seismic stations quickly. This study reiterates the value of joint seismo-acoustic data for improving interpretation of volcanic activity and reducing ambiguity in geophysical monitoring.

Myogenic tremor - a novel tremor entity.

Tremor is a common neurological symptom with a plethora of potential etiologies. Apart from physiological tremor, the vast majority of tremor syndromes are linked to a pacemaker in the central nervous system (CNS) or, less common, in the peripheral nervous system. Myogenic tremor is a novel tremor entity, first reported in 2019 and believed to originate in the muscle itself. In this review, we describe the clinical properties of myogenic tremor and discuss its presumed pathogenesis on the basis of all of the patient cases published so far. Myogenic tremor manifests itself as a high frequency, postural, and kinetic tremor with onset in infancy. To date, only myopathies affecting the contractile elements, in particular myosin and a myosin-associated protein, have been recognized to feature myogenic tremor. The generator of the tremor is believed to be located in the sarcomere, with propagation and amplification of sarcomeric oscillatory activity through CNS reflex loops, similar to neuropathic tremor. True myogenic tremor must be distinguished from centrally mediated tremor due to myopathies with central nervous system involvement, i.e., mitochondrial myopathies or myotonic dystrophies. The presence of myogenic tremor strongly points toward a sarcomere-associated mutation and may thus be a valuable clinical tool for the differential diagnosis of myopathies.

Symposium 2: Movement Disorders SY2.1. Evaluation of Tremor

Tremor is defined as an involuntary, rhythmic (regularly recurrent) and oscillatory (rotating around a central plane) movement of the body part. The evaluation of tremor should begin with careful history taking and a focused clinical examination on tremor phenomenology and associated neurological signs. The first step of the approach is to exclude tremor mimics such as myoclonus, clonus or other hyperkinetic movements. The second step is to carefully evaluate clinical features and establish whether the tremor is isolated or combined with other neurological problems and the predominant tremor is at rest or action. Tremor can be classified into syndromes depending on the characteristics (e.g. activation of tremor, distribution of tremor) and prominent additional signs. The common tremor syndromes during action are essential tremor, enhanced physiologic tremor, dystonic tremor, drug-induced tremor, cerebellar tremor, rubral tremor, and orthostatic tremor while the common tremor syndromes at rest are parkinsonian tremor. A detailed tremor history and neurological examination are usually enough for the clinical evaluation of tremor syndromes. However, the clinical presentations are sometimes complex and electrophysiologic investigations can be helpful in making the diagnosis of tremor subtypes. The basic neurophysiologic test is a multi-channel surface EMG combined with accelerometry to assess the distribution of tremor, tremor frequency, and amplitude during various types of activation of tremor, the effect of loading and distraction on tremor frequency and amplitude. The characteristics of central tremor syndromes are more stable tremor frequency and less influenced by loading compared to peripheral tremor syndromes. The peak tremor frequency can be overlapped among tremor subtypes but a unique tremor frequency can be found in some syndrome such as orthostatic tremor, cerebellar tremor and rubral tremor. The specific neurophysiologic procedures including distractibility and entrainment are sensitive and specific for functional tremors. Recently, more advanced neurophysiologic tests have emerged. There is a promising role of intermuscular coherence analysis in the differential diagnosis of tremor subtypes. Evaluation of tremor based on clinical and neurophysiological features are important, leading to the appropriate diagnosis and treatment.

P-MD009. A neurophysiological characteristic of holme’s tremor with thalamic lesion

Introduction. Holme’s tremor (HT) is defined as a slow frequency tremor with irregular amplitude that mostly occurs at rest and worsens with voluntary movements. Dystonia can be occurred with HT and almost all patients had thalamic lesions. The neurophysiological characteristics of HT are limited. The objective of this case report is to highlight the neurophysiological finding of HT with co-occurrence of dystonia from the thalamic lesion. Results. We reported a 46-year-old female patient with 13-year-history of left cerebellar infarction with bilateral vertebral artery dissection post left cerebellar hemispherectomy with full recovery. Recently she presented with left hemiparesis, hemiataxia and left hemianesthesia, diagnosed as the right thalamic hemorrhage. Seven months later, she developed irregular jerky movement of the left hand as well as dystonic posture. The neurophysiological test was done to distinguish among HT, myorhythmia and dystonic tremor. The one-axis accelerometer (ACC) was put on the left thumb and surface EMG was placed on the abductor pollicis brevis (APB), the flexor digitorum superficialis of the left index (FDS 2) and the left extensor indicis proprius (EIP). The ACC and EMG data showed regular sinusoidal movement of left hand at the peak frequency of 3 Hz with synchronous contractions of the antagonist pairs at rest. The similar pattern with larger amplitude of movement was demonstrated during postural holding at several positions. These findings were consistent with the definition of HT with concomitant dystonia rather than myorhythmia or dystonic tremor. The functional imaging also revealed hypometabolism of right thalamus, cerebral peduncle, medulla and left cerebellum. Botulinum toxin injection was done with good benefit. Conclusion. The neurophysiological test is capable to differentiate HT from mimics. Sinusoidal rhythmic slow oscillation with co-contraction of the antagonist pairs at rest with worsening at voluntary movements might indicate HT with concomitant dystonia.

White Matter Hyperintensities Are Associated With Severity of Essential Tremor in the Elderly.

Background: Essential tremor (ET) occurs with steeply increasing prevalence in the elderly, and apart from disease duration, age is independently associated with an increase of tremor amplitude and a decrease of frequency. White matter hyperintensities (WMHs) are a common finding in the elderly, and their role in the pathophysiology of ET is unknown. The aims of this study were to examine whether ET patients differ in their total or region-specific WMH volumes from healthy controls and to determine the impact of WMH on tremor characteristics.Methods: A total of 47 elderly ET patients with a mean age of 72 years and 39 age-matched healthy controls underwent a thorough clinical assessment and 3T MRI. Total WMH volumes were derived from T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Additionally, region of interest-based WMH volumes for the Johns Hopkins University (JHU) white matter tracts and labels were calculated, and WMHs were assessed semiquantitatively using the Fazekas scale.Results: Essential tremor patients and healthy controls did not differ in their total or tract-specific WMH volumes or Fazekas scores. However, WMH volume was significantly positively correlated with tremor severity on the TETRAS scale, and there was a significant negative correlation with the mean accelerometric tremor frequency. In a multiple linear regression model including disease duration, age, and age-adjusted total WMH volume, only the WMH volume significantly predicted tremor severity, while age and disease duration were not significant.Conclusion: We found evidence for a direct association between WMH volume and tremor severity. If confirmed by larger studies, our findings could explain the well-known relation between age and tremor severity.

Parkinson’s Disease Patient Monitoring: A Real-Time Tracking and Tremor Detection System Based on Magnetic Measurements

Reliable diagnosis of early-stage Parkinson’s disease is an important task, since it permits the administration of a timely treatment, slowing the progression of the disease. Together with non-motor symptoms, other important signs of disease can be retrieved from the measurement of the movement trajectory and from tremor appearances. To measure these signs, the paper proposes a magnetic tracking system able to collect information about translational and vibrational movements in a spatial cubic domain, using a low-cost, low-power and highly accurate solution. These features allow the usage of the proposed technology to realize a portable monitoring system, that may be operated at home or in general practices, enabling telemedicine and preventing saturation of large neurological centers. Validation is based on three tests: movement trajectory tracking, a rest tremor test and a finger tapping test. These tests are considered in the Unified Parkinson’s Disease Rating Scale and are provided as case studies to prove the system’s capabilities to track and detect tremor frequencies. In the case of the tapping test, a preliminary classification scheme is also proposed to discriminate between healthy and ill patients. No human patients are involved in the tests, and most cases are emulated by means of a robotic arm, suitably driven to perform required tasks. Tapping test results show a classification accuracy of about 93% using a k-NN classification algorithm, while imposed tremor frequencies have been correctly detected by the system in the other two tests.

MO204CHRONIC KIDNEY DISEASE, SLEEPINESS, MILD COGNITIVE IMPAIRMENT AND FINE MOTOR CONTROL

Abstract Background and Aims Chronic kidney disease (CKD) is a systemic condition because it modifies all organs' function due to an imbalance in plasma volume, electrolytes, hormones, and proteins. Indeed, at the nervous system level, mild cognitive impairment (MCI), sleep disorders and depression often accompany CKD. MCI partially explains the low quality of life of CKD patients, comparable to that of metastatic cancer patients. Mild Cognitive Impairment (MCI) has a high prevalence in this cohort (27-62%). Nevertheless, scattered literature data suggest that CKD patients can also have poor motor control, evidenced by a higher risk of falls, postural instability, reduced gait speed. In this cohort, few data are available regarding the motor circuits called central pattern generators, which control physiological tremor. Specifically, uraemic encephalopathy accentuates physiological tremor, which is regulated by central and peripheral oscillators. Overall, subtle changes in motor control often accompany other forms of MCI. Therefore, this study aimed at evaluating the effects of chronic kidney disease on cognitive and motor functions using up-to-date technologies to record physiological tremor and innovative data analysis. Method This retrospective case-control study enrolled 313 patients (139 controls, 79 CKD patients stage III-IV, 35 kidney transplant (Tx), 60 dialysis (HD) patients). These groups were comparable for age and weight. Creatininemia, azotemia, LDL, HDL, hemoglobin, and proteinuria were used for correlative analyses. We evaluated the chronotype using the Morningness-Eveningness Questionnaire (MEQ) and the degree of sleepiness using the Epworth Sleepiness Scale (ESS). Cognitive impairment was assessed by the Montreal Cognitive Assessment test (MoCA). Cognitive domains of the MoCA score were projected onto brain regions using CerebroViz library in R and a new transformation matrix derived from fMRI literature data. UMAP algorithm was used to identify patients' subgroups. The physiological tremor was recorded on patients maintaining the dominant arm extended using the smartphone App Phyphox. The tremor frequency spectrum was extracted by Fourier analysis. Results The sleepiness score (ESS) was significantly increased in HD (ESS = 5±0.4) compared to the healthy controls (ESS= 4±0.41) whereas was not significantly modified in CKD patients (3.24± 0.32). The chronotype was also not significantly different among the various groups. The mean score of the MoCA test was significantly lower in CKD, Tx, and HD groups (CKD MoCA =24.5±0.3; Tx MoCA =25.4±0.6; HD MoCA =24.6±0.7) than controls (MoCA score=28±0.1). A different pattern of impairment in the cognitive domains of MoCA was evidenced in the various groups using the CerebroViz projection and UMAP tools. MoCA score was inversely correlated with proteinuria (Pearson coefficient=-0.47; p&amp;lt;0.05). The higher frequencies of the physiological tremor (11-13 Hz) were significantly more represented in Tx patients compared to controls (p&amp;lt;0.05). Conversely, the lower frequencies (1-4 Hz) were significantly less represented in the HD group compared to controls (p&amp;lt;0.05). The peak frequency was inversely correlated with age in all patients (Pearson coefficient= -0.45; p&amp;lt;0.05) and inversely associated with azotemia levels, particularly in HD patients (Pearson coefficient=0.43; p&amp;lt;0.05). Conclusion Our results suggest that CKD patients present altered cognitive and motor control patterns, linked in part to the proteinuria level, suggesting a pathogenetic role of endothelial dysfunction. The characteristic motor, sleepiness and cognitive patterns of HD patients might be due to the arteriovenous fistula or the other peculiarities of these patients. These results might help identify new early markers of brain dysfunction in these patients, with the possibility of delaying or reversing cognitive decay.

Electroencephalography in Orthostatic Tremor: A Prospective Study of 30 Patients.

Background:Orthostatic tremor (OT) is characterized by a sensation of instability while standing, associated with high frequency (1318 Hz) tremor in the legs. Small retrospective series have reported electroencephalography (EEG) findings in OT with discordant results.Methods:We prospectively enrolled 30 OT subjects. Mean age = 68.3 (range 5487) with mean disease duration 16.3 years (range 444). A modified 1020 system EEG recording with additional midline electrodes was obtained. EMG electrodes were placed on quadricep muscles. EEG recording was performed at rest, during sleep and while standing unassisted.Results:In all subjects, EEG showed normal background, normal drowsiness and/or stage 2 sleep, and normal responses to hyperventilation and photic stimulation. These normal results persisted during stance. EEG abnormalities were found in 3 subjects (anterior-mid temporal slow activity), but were not position-dependent and were judged unlikely to be related to OT. Tremor artifact while standing was noted in all subjects, however it was measurable in 26 with frequency in the OT range in 25. When compared with EMG, the average difference in frequency was small at 1.2 Hz (range 0.52.5, p 0.46). Visual EEG analysis in OT patients did not reveal electrographic abnormalities even upon standing unassisted.Discussion:EEG was normal on this prospective, relatively large OT series. Clinicians interpreting video-EEGs should be aware of the OT artifact that can be seen in EEG and EKG leads mostly while standing.

Directionality of corticomuscular coupling in essential tremor and cortical myoclonic tremor

ObjectiveA role of the motor cortex in tremor generation in essential tremor (ET) is assumed, yet the directionality of corticomuscular coupling is unknown. Our aim is to clarify the role of the motor cortex. To this end we also study ‘familial cortical myoclonic tremor with epilepsy’ (FCMTE) and slow repetitive voluntary movements with a known cortical drive. MethodsDirectionality of corticomuscular coupling (EEG-EMG) was studied with renormalized partial directed coherence (rPDC) during tremor in 25 ET patients, 25 healthy controls (mimicked) and in seven FCMTE patients; and during a self-paced 2 Hz task in eight ET patients and seven healthy controls. ResultsEfferent coupling around tremor frequency was seen in 33% of ET patients, 45.5% of healthy controls, all FCMTE patients, and, around 2 Hz, in all ET patients and all healthy controls. Ascending coupling, seen in the majority of all participants, was weaker in ET than in healthy controls around 5–6 Hz. ConclusionsPossible explanations are that tremor in ET results from faulty subcortical output bypassing the motor cortex; rate-dependent transmission similar to generation of rhythmic movements; and/or faulty feedforward mechanism resulting from decreased afferent (sensory) coupling. SignificanceA linear cortical drive is lacking in the majority of ET patients.