Movement disorders in hereditary spastic paraplegias.

BACKGROUND: Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. OBJECTIVE: To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. METHODS: We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. RESULTS: Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. CONCLUSION: Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

ANTECEDENTES: As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. OBJETIVO: Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. MéTODOS: Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. RESULTADOS: O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. CONCLUSãO: Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Towards a Modular Pathological Tremor Simulation System Based on the Stewart Platform.

Wearable technologies have aided in reducing pathological tremor symptoms through non-intrusive solutions that aim to identify patterns in involuntary movements and suppress them using actuators positioned at specific joints. However, during the development of these devices, tests were primarily conducted on patients due to the difficulty of faithfully simulating tremors using simulation equipment. Based on studies characterizing tremors in Parkinson's disease, the development of a robotic manipulator based on the Stewart platform was initiated, with the goal of satisfactorily simulating resting tremor movements in the hands. In this work, a simulator was implemented in a computational environment using the multibody dynamics method. The platform structure was designed in a virtual environment using SOLIDWORKS® v2017 software and later exported to Matlab® R17a software using the Simulink environment and Simscape multibody library. The workspace was evaluated, and the Kalman filter was used to merge acceleration and angular velocity data and convert them into data related to the inclination and rotation of real patients' wrists, which were subsequently executed in the simulator. The results show a high correlation and low dispersion between real and simulated signals, demonstrating that the simulated mechanism has the capacity to represent Parkinson's disease resting tremors in all wrist movements. The system could contribute to conducting tremor tests in suppression devices without the need for the presence of the patient and aid in comparing suppression techniques, benefiting the development of new wearable devices.

The hand tremor spectrum is modified by the inertial sensor mass during lightweight wearable and smartphone-based assessment in healthy young subjects.

Tremors are common disorders characterized by an involuntary and relatively rhythmic oscillation that can occur in any part of the body and may be physiological or associated with some pathological condition. It is known that the mass loading can change the power spectral distribution of the tremor. Nowadays, many instruments have been used in the evaluation of tremors with bult-in inertial sensors, such as smartphones and wearables, which can significantly differ in the device mass. The aim of this study was to compare the quantification of hand tremor using Fourier spectral techniques obtained from readings of accelerometers built-in a lightweight handheld device and a commercial smartphone in healthy young subjects. We recruited 28 healthy right-handed subjects with ages ranging from 18 to 40 years. We tested hand tremors at rest and postural conditions using lightweight wearable device (5.7 g) and smartphone (169 g). Comparing both devices at resting tremor, we found with smartphone the power distribution of peak ranging 5 and 12 Hz in both hands. With wearable, the result was similar but less evident. When comparing both devices in postural tremor, there were significant differences in both frequency ranges in peak frequency and peak amplitude in both hands. Our main findings show that in resting condition the hand tremor spectrum had a higher peak amplitude in the 5-12 Hz range when the tremor was recorded with smartphones, and in postural condition there was a significantly (p < 0.05) higher peak power spectrum and peak frequency in the dominant hand tremors recorded with smartphones compared to those obtained with lightweight wearable device. Devices having different masses can alter the features of the hand tremor spectrum and their mutual comparisons can be prejudiced.

Drug-induced tremor, clinical features, diagnostic approach and management.

Tremor is the most common movement disorder and there are numerous causes of tremor. In many individuals, tremor can be due to drugs. The most common drugs associated with tremor include amiodarone, selective serotonin (and norepinephrine) reuptake inhibitors (SSRIs/SNRIs), amitriptyline, lithium, valproate, ß-adrenoceptor agonists, dopamine receptor antagonists, VMAT2 inhibitors, or drugs of abuse: ethanol, cocaine, etc. Drug-induced tremor usually resembles essential or parkinsonian tremor, depending on the offending drug; however, features such as unilateral, task-specific, position-dependent tremor or sudden onset, distractibility, entrainment and arrest with contralateral movements suggest etiologies such as dystonic or functional (psychogenic) tremor. Risk factors for drug-induced tremor include polypharmacy, male gender, older age, high doses and immediate-release preparations or reaching toxic levels of the offending drugs. Drug-induced tremor usually resolves once the offending medication is discontinued, however, persistent tremor may be observed in some cases (tardive tremor). In this manuscript, we discuss the most common causes of drug-induced tremor. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.

On the use of histograms of oriented gradients for tremor detection from sinusoidal and spiral handwritten drawings of people with Parkinson's disease.

Parkinson's disease (PD), whose cardinal signs are tremor, rigidity, bradykinesia, and postural instability, gradually reduces the quality of life of the patient, making early diagnosis and follow-up of the disorder essential. This study aims to contribute to the objective evaluation of tremor in PD by introducing and assessing histograms of oriented gradients (HOG) to the analysis of handwriting sinusoidal and spiral patterns. These patterns were digitized and collected from handwritten drawings of people with PD (n = 20) and control healthy individuals (n = 20). The HOG descriptor was employed to represent relevant information from the data classified by three distinct machine-learning methods (random forest, k-nearest neighbor, support vector machine) and a deep learning method (convolutional neural network) to identify tremor in participants with PD automatically. The HOG descriptor allowed for the highest discriminating rates (accuracy 83.1%, sensitivity 85.4%, specificity 80.8%, area under the curve 91%) on the test set of sinusoidal patterns by using the one-dimensional convolutional neural network. In addition, ANOVA and Tukey analysis showed that the sinusoidal drawing is more appropriate than the spiral pattern, which is the most common drawing used for tremor detection. This research introduces a novel and alternative way of quantifying and evaluating tremor by means of handwritten drawings.

Valproate-induced rest tremor and parkinsonism.

Tremor and parkinsonism are recognized side effects of valproate; however, the relationship between rest tremor and other signs of parkinsonism has not been addressed in patients taking valproate. We studied a cohort of 125 consecutive patients treated with valproate due to epilepsy or migraine, evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). A total of 14 (11.2%) patients had rest tremor (bilateral n = 10, unilateral n = 4). Patients with rest tremor had significant higher scores in the FTM-TRS (P < 0.001), but only one was diagnosed with parkinsonism. Patients may have valproate-induced parkinsonism or exacerbated motor features of Parkinson's disease by valproate. The frequency of parkinsonism was 1.6% in this cohort and of 3% in the pooled data of 717 patients from previous reports. Rest tremor is observed in 11.2% of patients treated with valproate and is related to the burden of valproate-induced tremor, rather than the presence of parkinsonism.

How can neurophysiological studies help with movement disorders characterization in clinical practice? A review.

BACKGROUND: Neurophysiological studies are ancillary tools to better understand the features and nature of movement disorders. Electromyography (EMG), together with electroencephalography (EEG) and accelerometer, can be used to evaluate a hypo and hyperkinetic spectrum of movements. Specific techniques can be applied to better characterize the phenomenology, help distinguish functional from organic origin and assess the most probable site of the movement generator in the nervous system. OBJECTIVE: We intend to provide an update for clinicians on helpful neurophysiological tools to assess movement disorders in clinical practice. METHODS: Non-systematic review of the literature published up to June 2019. RESULTS: A diversity of protocols was found and described. These include EMG analyses to define dystonia, myoclonus, myokymia, myorhythmia, and painful legs moving toes pattern; EMG in combination with accelerometer to study tremor; and EEG-EMG to study myoclonus. Also, indirect measures of cortical and brainstem excitability help to describe and diagnose abnormal physiology in Parkinson's disease, atypical parkinsonism, dystonia, and myoclonus. CONCLUSION: These studies can be helpful for the diagnosis and are usually underutilized in neurological practice.

How can neurophysiological studies help with movement disorders characterization in clinical practice? A review / Como os exames neurofisiológicos podem ajudar na caracterização dos transtornos do movimento na prática clínica? Uma revisão

ABSTRACT Background: Neurophysiological studies are ancillary tools to better understand the features and nature of movement disorders. Electromyography (EMG), together with electroencephalography (EEG) and accelerometer, can be used to evaluate a hypo and hyperkinetic spectrum of movements. Specific techniques can be applied to better characterize the phenomenology, help distinguish functional from organic origin and assess the most probable site of the movement generator in the nervous system. Objective: We intend to provide an update for clinicians on helpful neurophysiological tools to assess movement disorders in clinical practice. Methods: Non-systematic review of the literature published up to June 2019. Results: A diversity of protocols was found and described. These include EMG analyses to define dystonia, myoclonus, myokymia, myorhythmia, and painful legs moving toes pattern; EMG in combination with accelerometer to study tremor; and EEG-EMG to study myoclonus. Also, indirect measures of cortical and brainstem excitability help to describe and diagnose abnormal physiology in Parkinson's disease, atypical parkinsonism, dystonia, and myoclonus. Conclusion: These studies can be helpful for the diagnosis and are usually underutilized in neurological practice.

RESUMO Introdução: Os estudos neurofisiológicos são métodos auxiliares para compreender melhor as características e a natureza dos distúrbios do movimento. A eletromiografia (EMG), em associação com o eletroencefalograma (EEG) e o acelerômetro, podem ser utilizados para avaliar um espectro de movimentos hipo e hipercinéticos. Técnicas específicas podem ser aplicadas para melhor caracterizar a fenomenologia, ajudar a distinguir a origem psicogênica da orgânica e avaliar o local mais provável de geração do movimento no sistema nervoso. Objetivo: Pretendemos fornecer ao clínico uma atualização sobre ferramentas neurofisiológicas úteis para avaliar distúrbios do movimento na prática clínica. Métodos: Revisão não sistemática da literatura publicada até junho de 2019. Resultados: Uma diversidade de protocolos foi encontrada e descrita. Dentre eles, inclui-se o uso de EMG para a definição do padrão de distonia, mioclonia, mioquimia, miorritmia e painfull legs moving toes, além do uso de EMG em associação ao acelerômetro para avaliar tremor e, em associação ao EEG para avaliar mioclonia. Ademais, técnicas para medida indireta de excitabilidade cortical e do tronco encefálico ajudam a descrever e diagnosticar a fisiologia anormal da doença de Parkinson, parkinsonismo atípico, distonia e mioclonia. Conclusão: Esses estudos podem ser úteis para o diagnóstico e geralmente são subutilizados na prática neurológica.

Item Response Theory Analysis of the MDS-UPDRS Motor Examination: Tremor vs. Nontremor Items.

BACKGROUND: In PD, tremor severity behaves differently from other core motor features. However, the most commonly used assessment of overall motor severity, total MDS-UPDRS Motor Examination (Part 3) score, does not account for this distinction. OBJECTIVES: To investigate the Motor Examination (Part 3) using Item Response Theory approaches focusing on sample-independent strategies that assess how well items measure latent models of PD motor severity. METHODS: Data from 6,298 PD patients were analyzed with graded response model Item Response Theory approaches involving two analyses all 33 Part 3 items versus the 10 tremor items and 23 bradykinesia, rigidity, gait, and posture items considered separately. The strength of relationship between items and the latent measure of parkinsonian motor severity (discrimination parameter) and calculated thresholds (location parameters) were assessed using the mirt program implemented in R (R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Analyzing all Part 3 items together, nontremor items demonstrated good discrimination parameters (mean = 1.83 ± 0.37) and range of thresholds (-1.73 to +4.42), but tremor items had poor discrimination (mean = 0.52 ± 0.76) and thresholds (-0.69 to 14.29). Segregating nontremor from tremor items in two independent analyses provided markedly improved discrimination and location parameters for both. CONCLUSIONS: MDS-UPDRS Part 3 tremor and nontremor items have very different relations to the construct of PD severity. Strongly improved clinimetric properties for Part 3 are obtained when tremor and nontremor items are considered separately. We suggest that evaluating PD motor severity, as an operationalized summary measure, is best attained through separate analyses with tremor and nontremor motor scores. © 2020 International Parkinson and Movement Disorder Society.

Motor Dysfunction as a Prodrome of Parkinson's Disease.

BACKGROUND: Recognition of motor signs in the prodromal stage could help identify those at risk of developing Parkinson's disease (PD). OBJECTIVE: This study identified motor symptoms and signs in individuals suspected of having PD but who did not have a progressive reduction in the speed and amplitude of finger tapping or other physical signs indicative of bradykinesia. METHODS: 146 patients, who had symptoms or signs suggestive of PD, were serially evaluated by a movement disorder specialist, using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and video recordings. If the patients 'converted' to PD during follow-up, they were categorized as cases and compared with those who did not meet PD criteria during follow-up (non-cases). RESULTS: The 82 cases were more likely to have action dystonia or postural/action/rest tremor of a limb (OR 2.8; 95% CI 1.1-7.1; p = 0.02), a reduced blink rate at rest (OR 2.3; 95% CI 1.2-4.6; p = 0.01), anxiety (OR 8.9; 95% CI 2.6-31.1; p < 0.001), depression (OR 7.0; 95% CI 2.9-17.2; p < 0.001), or a frozen shoulder (OR 3.1; 95% CI 1.6-6.2) than the 64 'non-cases'.A reduction of the fast blink rate was common in patients who met the criteria for PD (p < 0.001). CONCLUSIONS: This study emphasizes that motor dysfunction is a component of the clinical prodrome seen in some patients with PD.

Contrast and Homogeneity Feature Analysis for Classifying Tremor Levels in Parkinson's Disease Patients.

Early detection of different levels of tremors helps to obtain a more accurate diagnosis of Parkinson's disease and to increase the therapy options for a better quality of life for patients. This work proposes a non-invasive strategy to measure the severity of tremors with the aim of diagnosing one of the first three levels of Parkinson's disease by the Unified Parkinson's Disease Rating Scale (UPDRS). A tremor being an involuntary motion that mainly appears in the hands; the dataset is acquired using a leap motion controller that measures 3D coordinates of each finger and the palmar region. Texture features are computed using sum and difference of histograms (SDH) to characterize the dataset, varying the window size; however, only the most fundamental elements are used in the classification stage. A machine learning classifier provides the final classification results of the tremor level. The effectiveness of our approach is obtained by a set of performance metrics, which are also used to show a comparison between different proposed designs.

Stereotactic Lesion in the Forel's Field H: A 2-Years Prospective Open-Label Study on Motor and Nonmotor Symptoms, Neuropsychological Functions, and Quality of Life in Parkinson Disease.

BACKGROUND: Stereotactic lesion in the Forel's field H (campotomy) was proposed in 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on this approach have emerged. Additionally, no study has assessed its effects on nonmotor symptoms, neuropsychological functions and quality of life. OBJECTIVE: To provide a prospective 2-yr assessment of motor, nonmotor, neuropsychological and quality of life variables after unilateral campotomy. METHODS: Twelve PD patients were prospectively evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson's disease quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, neuropsychiatric, neuropsychological and quality of life variables were assessed. The impact of PD on global health was also rated. RESULTS: A significant reduction in contralateral rest tremor (65.7%, P < .001), rigidity (87.8%, P < .001), bradykinesia (68%, P < .001) and axial symptoms (24.2%, P < .05) in offmedication condition led to a 43.9% reduction in UPSDRS III scores 2 yr after campotomy (P < .001). Gait improved by 31.9% (P < .05) and walking time to cover 7 m was reduced by 43.2% (P < .05). Pain decreased by 33.4% (P < .01), while neuropsychiatric and neuropsychological functions did not change. Quality of life improved by 37.8% (P < .05), in line with a 46.7% reduction of disease impact on global health (P < .001). CONCLUSION: A significant 2-yr improvement of motor symptoms, gait performance and pain was obtained after unilateral campotomy without significant changes to cognition. Quality of life markedly improved in parallel with a significant reduction of PD burden on global health.

Resting Tremor after Mild Head Injury: Case Report

Over the past few decades, it has been recognized that traumatic brain injury (TBI) may result in various movement disorders. However, moderate or mild TBI only rarely causes persistent post-traumatic movement disorders. In the present report, we describe a case of secondary tremor due to amild head injury with a transitory loss of consciousness. A 26- year-old man developed an isolated rest tremor of the hands and legs without other neurologic signs. The interval between the head trauma and the onset of the symptomswas 4 months. Neuroimaging studies reveled gliosis in the lentiform nucleus. Haloperidol administration resulted in tremor reduction. A rest tremor, similar to essential tremor, can be a rare complication of head trauma. Haloperidolmay be an effective and safe treatment modality for post-traumatic tremor. Further studies are needed to clarify the optimal drug for the treatment of post-traumatic tremor.

Sensitivity and specificity of different hand positions to assess upper limb rest tremor.

BACKGROUND: Hand position for rest tremor evaluation in PD is not standardized. We evaluated the sensitivity and specificity of different hand positions commonly used to evaluate rest tremor. METHODS: Twenty patients with PD and rest tremor were included as cases and 20 patients with essential tremor without rest tremor as controls. Video and accelerometric recordings were conducted in semiprone, completely prone, and with hands hanging down from armrest positions. Three movement disorder specialists rated tremor in each different position using Movement Disorder Society UPDRS items 3.17 and 3.18. RESULTS: Hands hanging showed the highest amplitude (P = 0.004) and constancy (P = 0.015) scores. Sensitivity and specificity analysis for each position showed the following sensitivity/specificity results: semiprone, 95%/80%; completely prone, 85%/98.33%; and hands hanging, 96.66%/63.33%, respectively. CONCLUSIONS: The hands-hanging position was shown to be the most suitable for evaluating rest tremor amplitude in PD, whereas the completely prone position proved to be more specific to detect rest tremor. The preferred hand position would depend on the purpose of the examination. © 2019 International Parkinson and Movement Disorder Society.

A Treatable Rare Cause of Progressive Ataxia and Palatal Tremor.

Background: Cerebrotendinous xanthomatosis is a rare autosomal recessive neurometabolic disorder characterized by chronic diarrhea, tendon xanthomas, juvenile cataracts, and neurological symptoms. Case Report: An adult patient with cerebrotendinous xanthomatosis exhibited ataxia and palatal tremor in the absence of tendon xanthomas and cataracts. Discussion: The importance of this case resides on the fact that cerebrotendinous xanthomatosis should be considered as a possible etiology of the syndrome of progressive ataxia with palatal tremor, even in the absence of tendon xanthomas and cataracts. Early diagnosis is critical to the institution of specific treatment with chenodeoxycholic acid.