[Analysis of 9 patients with adolescence-onset methylenetetrahydrofolate reductase deficiency].

Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 µmol/L) was found in all patients, and decreased to 20-70 µmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Patterns and assessment of spastic hemiplegic gait.

Hemiparetic gait disorders are common in stroke survivors. A circumductory gait is often considered the typical hemiparetic gait. In clinical practice, a wide spectrum of abnormal gait patterns is observed, depending on the severity of weakness and spasticity, and the anatomical distribution of spasticity. Muscle strength is the key determinant of gait disorders in hemiparetic stroke survivors. Spasticity and its associated involuntary activation of synergistic spastic muscles often alter posture of involved joint(s) and subsequently the alignment of hip, knee, and ankle joints, resulting in abnormal gait patterns. Due to combinations of various levels of muscle weakness and spasticity and their interactions with ground reaction force, presentations of gait disorders are variable. From a neuromechanical perspective, a stepwise visual gait analysis approach is proposed to identify primary underlying causes. In this approach, the pelvic and hip joint movement is examined first. The pelvic girdle constitutes three kinematic determinants. Its abnormality determines the body vector and compensatory kinetic chain reactions in the knee and ankle joints. The second step is to assess the ankle and foot complex abnormality. The last step is to examine abnormality of the knee joint. Assessment of muscle strength and spasticity of hip, knee, and ankle/foot joints needs to be performed before these steps. Lidocaine nerve blocks can be a useful diagnostic tool. Recognizing different patterns and identifying the primary causes are critical to developing clinical interventions to improve gait functions.

Neuro-orthopaedic assessment and management in patients with prolonged disorders of consciousness: A review.

BACKGROUND: Following a severe acquired brain injury, neuro-orthopaedic disorders are commonplace. While these disorders can impact patients' functional recovery and quality of life, little is known regarding the assessment, management and treatment of neuro-orthopaedic disorders in patients with disorders of consciousness (DoC). OBJECTIVE: To describe neuro-orthopaedic disorders in the context of DoC and provide insights on their management and treatment. METHODS: A review of the literature was conducted focusing on neuro-orthopaedic disorders in patients with prolonged DoC. RESULTS: Few studies have investigated the prevalence of spastic paresis in patients with prolonged DoC, which is extremely high, as well as its correlation with pain. Pilot studies exploring the effects of pharmacological treatments and physical therapy show encouraging results yet have limited efficacy. Other neuro-orthopaedic disorders, such as heterotopic ossification, are still poorly investigated. CONCLUSION: The literature of neuro-orthopaedic disorders in patients with prolonged DoC remains scarce, mainly focusing on spastic paresis. We recommend treating neuro-orthopaedic disorders in their early phases to prevent complications such as pain and improve patients' recovery. Additionally, this approach could enhance patients' ability to behaviourally demonstrate signs of consciousness, especially in the context of covert awareness.

An integrated rehabilitation system for the upper limb spasticity assessment and treatment: the Rehabotics passive exoskeletal system.

Limb spasticity is caused by stroke, multiple sclerosis, traumatic brain injury and various central nervous system pathologies such as brain tumors resulting in joint stiffness, loss of hand function and severe pain. This paper presents with the Rehabotics integrated rehabilitation system aiming to provide highly individualized assessment and treatment of the function of the upper limbs for patients with spasticity after stroke, focusing on the developed passive exoskeletal system. The proposed system can: (i) measure various motor and kinematic parameters of the upper limb in order to evaluate the patient's condition and progress, as well as (ii) offer a specialized rehabilitation program (therapeutic exercises, retraining of functional movements and support of daily activities) through an interactive virtual environment. The outmost aim of this multidisciplinary research work is to create new tools for providing high-level treatment and support services to patients with spasticity after stroke.Clinical Relevance- This paper presents a new passive exoskeletal system aiming to provide enhanced treatment and assessment of patients with upper limb spasticity after stroke.

Validity of Accelerometer-Based Sensor System for Muscle Tightness Estimation through Vibration on the Upper Limb.

Spasticity is a condition that profoundly impacts the ability to perform everyday tasks. However, its diagnosis requires trained physicians and subjective evaluations that may vary depending on the evaluator. Focal vibration of spastic muscles has been proposed as a non-invasive, pain-free alternative for spasticity modulation. We propose a system to estimate muscular tightness based on the propagation of elastic waves in the skin generated by focal vibration of the upper limb. The developed system generates focalized displacements on the biceps muscle at frequencies from 50 to 200 Hz, measures the vibration acceleration on the vibration source (input) and the distant location (output), and extracts features of ratios between input and output. The system was tested on 5 healthy volunteers while lifting 1.25 - 11.25 kg weights to increase muscle tone resembling spastic conditions, where the vibration frequency and weight were selected as explanatory variables. An increase in the ratio of the root mean squares proportional to the weight was found, validating the feasibility of the current approach to estimating muscle tightness.Clinical Relevance- This work presents the feasibility of a vibration-based system as an alternative method to objectively diagnose the degree of spasticity.

Using sEMG Signal Frequency to Evaluate Post-Stroke Elbow Spasticity.

Spasticity is a motor disorder with high prevalence and critical consequences following a stroke. Reliable and sensitive measurements are important to guide the selection and evaluation of treatment strategies. Technology-assisted methods, such as the surface electromyography (sEMG) technique, have been developed to measure spasticity as sensitive and accurate alternatives to commonly used clinical scales. However, sEMG amplitude based measures may confound spasticity-induced muscle activities with other types of muscle contractions. This study thus introduces the idea of using sEMG frequency information to detect spasticity as a potential solution to overcome the limitations of existing sEMG based measures. The preliminary results of three patients demonstrate the possibility and future research directions for this approach.

Spasticity assessment with muscle coactivation of elbow flexors during passive stretch in Post-stroke Hemiplegia.

the assessment of muscle properties is an essential prerequisite in the treatment of post-stroke muscle spasticity. Previous studies have shown that muscle coactivation, which reflects the simultaneous activation of agonist and antagonist muscle groups, is associated with muscle spasticity during voluntary contraction. However, current spasticity assessment approaches do not often consider muscle coactivation for passive contraction measured with surface electromyography (sEMG). The purpose here is to evaluate the validity and reliability of muscle co-activation based on sEMG for assessing spasticity of post-stroke patients. This study was conducted on 39 chronic hemiplegia post-stroke patients with varying degrees of elbow flexor spasticity. The severity of spasticity was assessed with Modified Ashworth Scale (MAS). The patients produced elbow flexion passively on affected arm. Two-channel surface sEMG recordings were acquired simultaneously for the biceps and triceps muscles. The effectiveness and reliability of the EMG-based spasticity assessment method were evaluated using Spearman's correlation analysis and intra class correlation coefficients (ICCs). The results showed that there was a statistically significant positive relationship between the level of activity and the coactivation index (R=0.710, P=0.003), while the ICCs for intra trial measures ranged between 0.928 and 0.976. Muscle coactivation is a promising tool for continuously quantifying muscle spasticity in post-stroke patients, suggesting that the EMG-based muscle coactivation index could be useful for assessing motor function.

[Surgical procedures for treatment of spasticity]. / Chirurgische Verfahren zur Therapie von Spastik.

BACKGROUND: The causes of spasticity are various and include cerebral palsy, spinal cord injury, stroke, multiple sclerosis or other congenital or acquired lesions of the central nervous system (CNS). While there is often a partial functional component, spasticity also results in varying degrees of impairment of the quality of life. OBJECTIVE: A review of surgical treatment options for spasticity. MATERIAL AND METHODS: A systematic PubMed review of the literature on epidemiology and treatment options with a focus on neurosurgical interventions for spasticity and developments in the last 20 years as well as inclusion of still valid older landmark papers was carried out. Illustration of indications, technique, follow-up, and possible pitfalls of the different methods for the surgical treatment of spasticity. RESULTS: Depending on the affected region, the number of muscle groups, and the extent of spasticity, focal (selective peripheral neurotomy, nerve transfer), regional (selective dorsal rhizotomy), or generalized (baclofen pump) procedures can be performed. The indications are usually established by an interdisciplinary team. Conservative (physiotherapy, oral medications) and focally invasive (botulinum toxin injections) methods should be performed in advance. In cases of insufficient response to treatment or only short-term relief, surgical methods can be evaluated. These are usually preceded by test phases with, for example, trial injections. CONCLUSION: Surgical methods are a useful adjunct in cases of insufficient response to conservative treatment in children and adults with spasticity.

Comparison of the immediate effects of plantar vibration of both feet with the plantar vibration of the affected foot on balance in patients with stroke: Preliminary findings.

OBJECTIVE: Plantar vibration is one of the strategies to enhance balance in stroke patients. This study compared the effects of the plantar vibration of both feet and the plantar vibration of the most affected side in patients with stroke. METHODS: This study was a single-blind clinical trial. Post-stroke patients with balance impairment were enrolled in the study and underwent two treatment sessions with a one-week interval. They received both feet's plantar vibration in one session and plantar vibration of the most affected side in the other session (frequency 100 Hz, 5 min). Mini-BESTest, Modified Modified Ashworth Scale (MMAS), and Semmes-Weinstein monofilament examination (SWME) were used to evaluate balance, spasticity, and plantar sensation, before and after the treatment sessions. RESULTS: Ten patients with a mean age of 52.9 (SD = 5.48) years were enrolled in the study. Mini-BESTest scores of balance and plantar flexor muscle spasticity were significantly improved after both feet plantar vibration and plantar vibration of the more affected side. There was no significant difference between the effectiveness of both sides plantar vibration and the most affected side plantar vibration. There were no significant improvements in SWME sensory scores after plantar vibration of either both sides or the most affected side. CONCLUSION: Plantar vibration of both sides had no additional benefits in this group of patients with chronic stroke. Plantar vibration of more affected side can be used for improving balance and plantar flexor spasticity post-stroke. The Plantar vibration had no effects on the affected foot sensibility.

Expert consensus on the surgical evaluation and management of upper extremity spasticity in adults.

In the last decade there has been incredible interest and advancement in the surgical care of adult patients with upper motor neuron (UMN) injuries. Spasticity represents a prevalent and debilitating feature of UMN syndrome, which can result from cerebral palsy, spinal cord injury, cerebrovascular accident and traumatic or anoxic brain injury. While several diagnostic tools and management strategies have been described for upper limb spasticity, evidence-based practice guidelines do not currently exist due to low patient volume and a paucity of surgeons routinely performing surgeries in UMN syndrome patients. As such, expert consensus may help provide guidance for patients, therapists and clinicians alike. In this article an expert panel was assembled, and the Delphi method was utilized to present diagnostic considerations, define operative indications, discuss surgical treatment modalities and encourage a standard set of outcome measures for patients with upper extremity spasticity.

Clinical Reasoning: A 48-Year-Old Man With Spasticity and Progressive Ataxia.

A 48-year-old man was referred to the movement disorders clinic for 10 years of progressive slurred speech, spasticity, limb incoordination, and wide-based gait. Extensive neurologic workup was inconclusive, including serum and CSF testing, neuroimaging, EMG/NCS, exome sequencing, and mitochondrial testing. An ataxia repeat expansion panel ultimately revealed the final diagnosis. In this report, we review the clinical characteristics of a rare, late-onset, autosomal recessive cerebellar ataxia and discuss the importance of pursuing targeted gene testing to avoid diagnostic delays, especially as new treatments for this and other genetic diseases become available.

Modeling, Control, and Clinical Validation of an Upper-Limb Medical Education Task Trainer for Elbow Spasticity and Rigidity Assessment.

The goal of this study was to validate a series elastic actuator (SEA)-based robotic arm that can mimic three abnormal muscle behaviors, namely lead-pipe rigidity, cogwheel rigidity, and spasticity for medical education training purposes. Key characteristics of each muscle behavior were first modeled mathematically based on clinically-observed data across severity levels. A controller that incorporated feedback, feedforward, and disturbance observer schemes was implemented to deliver haptic target muscle resistive torques to the trainee during passive stretch assessments of the robotic arm. A series of benchtop tests across all behaviors and severity levels were conducted to validate the torque estimation accuracy of the custom SEA (RMSE: ~ 0.16 Nm) and the torque tracking performance of the controller (torque error percentage: < 2.8 %). A clinical validation study was performed with seven experienced clinicians to collect feedback on the task trainer's simulation realism via a Classification Test and a Disclosed Test. In the Classification Test, subjects were able to classify different muscle behaviors with a mean accuracy > 87 % and could further distinguish severity level within each behavior satisfactorily. In the Disclosed Test, subjects generally agreed with the simulation realism and provided suggestions on haptic behaviors for future iterations. Overall, subjects scored 4.9 out of 5 for the potential usefulness of this device as a medical education tool for students to learn spasticity and rigidity assessment.

Assessment of the quality and reliability of the information on spasticity on youtube.

BACKGROUND: Youtube has become an influential source of health. This study aimed to evaluate the reliability and quality of YouTube videos on spasticity. METHODS: The keywords " spasticity, spasticity treatment, spasticity exercises" were used to search for videos. According to the search results, 180 videos were analyzed, videometric characteristics of the videos were recorded, and 2 groups were formed as health professionals and non-health professionals according to the video source. In addition, low, medium and high quality groups were formed using the global quality score (GQS). The reliability of the videos was evaluated using the modified DISCERN (mDISCERN) scale. Video popularity was assessed using the video power index (VPI). RESULTS: After excluding videos that met the exclusion criteria, the remaining 68 videos were analyzed. The videos were uploaded by healthcare professionals (n = 47, 69.1%) and non-healthcare professionals (n = 21, 30.9%). The popularity (VPI), reliability (mDISCERN) and quality (GQS) of videos uploaded by healthcare professionals were significantly higher (p = 0.002, p = 0.001, p = 0.021, respectively). Most of the videos were of high quality according to GQS (n = 40, 58.8%). All of the high quality videos were of healthcare professionals. The number of sources from healthcare professionals was significantly higher in high quality videos than in both low (p = 0.001) and medium (p = 0.001) quality videos. CONCLUSION: We can conclude that most of the YouTube videos on spasticity are reliable and of high quality. However, it should be kept in mind that patients may be exposed to low-quality and unreliable videos with misleading content.

Application of tenotomy on Korean native cattle (Hanwoo) with spastic paresis symptoms in the field.

Bovine spastic paresis (BSP) is a neuromuscular disorder characterized by hypertension and stiffness of hindlimb. Two Korean native cattle (Hanwoo) calves developed BSP or BSP-like symptoms, and a tenotomy of superficial tendon of medial head and deep tendon of lateral head of gastrocnemius muscle was performed for treatment. A cast was applied postoperatively to prevent muscle rupture and was removed three weeks later. The prognosis was evaluated at 3 weeks, 6 and 18 months postoperatively. Neither calf showed any other postoperative sequelae. This is the first case study to report the diagnosis, treatment, and prognosis of BSP in Hanwoo.

Spasticity evaluation and management tools.

Spasticity is a complex and often disabling symptom for patients with upper motor neuron syndromes. Although spasticity arises from neurological disease, it often cascades into muscle and soft tissue changes, which may exacerbate symptoms and further hamper function. Effective management therefore hinges on early recognition and treatment. To this end, the definition of spasticity has expanded over time to more accurately reflect the spectrum of symptoms experienced by persons with this disorder. Once identified, clinical and research quantitative assessments of spasticity are hindered by the uniqueness of presentations both for individuals and for specific neurological diagnoses. Objective measures in isolation often fail to reflect the complex functional impact of spasticity. Multiple tools exist to quantitatively or qualitatively assess the severity of spasticity, including clinician and patient-reported measures as well as electrodiagnostic, mechanical, and ultrasound measures. A combination of objective and patient-reported outcomes is likely required to better reflect the burden of spasticity symptoms in an individual. Therapeutic options exist for the treatment of spasticity along a broad spectrum from nonpharmacologic to interventional procedures. Treatment strategies may include exercise, physical agent modalities, oral medications, injections, pumps, and surgery. Optimal spasticity management most often requires a multimodal approach, combining pharmacological management with interventions that match the functional needs, goals, and preferences of the patient. Physicians and other healthcare providers who manage spasticity must be familiarized with the full array of spasticity interventions and must frequently reassess results of treatment to ensure the patient's goals of treatment are met.

Reliability and validity of the Turkish version of the Selective Control Assessment of the Lower Extremity (SCALE) in children with spastic cerebral palsy.

PURPOSE: This study aims to translate the Selective Control Assessment of the Lower Extremity (SCALE) into Turkish language, assess its reliability and validity in children with spastic cerebral palsy. MATERIALS AND METHODS: Fifty-two children with CP (mean age 9 years 8 months, range 4-18 years) included in this cross-sectional study. Intra- and interrater reliability was assessed by intraclass correlation coefficient (ICC). The SCALE was correlated with the Gross Motor Function Classification System (GMFCS), the Physician's Rating Scale (PRS), and Gross Motor Function Measurement (GMFM) to assess validity. RESULTS: Intra- and interrater reliability of the SCALE were excellent (ICC > 0.75). SCALE and GMFCS (r = -0.786, p < 0.001), SCALE and PRS (r = 0.761, p < 0.001), SCALE and GMFM (r = 0.863, p < 0.001) were highly correlated. SCALE scores differed significantly between GMFCS levels and between types of spastic CP. CONCLUSIONS: The Turkish version of the SCALE appears to be a valid and reliable tool to assess selective voluntary motor control of the lower limbs in children with spastic CP.IMPLICATIONS FOR REHABILITATIONThe Turkish version of the Selective Control Assessment of the Lower Extremity is a valid and reliable assessment for children with spastic CP.The SCALE scores differed significantly between Gross Motor Function Classification System levels I versus II and levels II versus III as well as between types of spastic CP.The current study suggests that the SCALE is a quick and easy outcome measure to assess selective motor control in patients with spastic CP.

A Velocity Stretch Reflex Threshold Based on Muscle-Tendon Unit Peak Acceleration to Detect Possible Occurrences of Spasticity during Gait in Children with Cerebral Palsy.

Spasticity might affect gait in children with cerebral palsy. Quantifying its occurrence during locomotion is challenging. One approach is to determine kinematic stretch reflex thresholds, usually on the velocity, during passive assessment and to search for their exceedance during gait. These thresholds are determined through EMG-Onset detection algorithms, which are variable in performance and sensitive to noisy data, and can therefore lack consistency. This study aimed to evaluate the feasibility of determining the velocity stretch reflex threshold from maximal musculotendon acceleration. Eighteen children with CP were recruited and underwent clinical gait analysis and a full instrumented assessment of their soleus, gastrocnemius lateralis, semitendinosus, and rectus femoris spasticity, with EMG, kinematics, and applied forces being measured simultaneously. Using a subject-scaled musculoskeletal model, the acceleration-based stretch reflex velocity thresholds were determined and compared to those based on EMG-Onset determination. Their consistencies according to physiological criteria, i.e., if the timing of the threshold was between the beginning of the stretch and the spastic catch, were evaluated. Finally, two parameters designed to evaluate the occurrence of spasticity during gait, i.e., the proportion of the gait trial time with a gait velocity above the velocity threshold and the number of times the threshold was exceeded, were compared. The proposed method produces velocity stretch reflex thresholds close to the EMG-based ones. For all muscles, no statistical difference was found between the two parameters designed to evaluate the occurrence of spasticity during gait. Contrarily to the EMG-based methods, the proposed method always provides physiologically consistent values, with median electromechanical delays of between 50 and 130 ms. For all subjects, the semitendinosus velocity during gait usually exceeded its stretch reflex threshold, while it was less frequent for the three other muscles. We conclude that a velocity stretch reflex threshold, based on musculotendon acceleration, is a reliable substitute for EMG-based ones.

Technology-assisted assessment of spasticity: a systematic review.

BACKGROUND: Spasticity is defined as "a motor disorder characterised by a velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks". It is a highly prevalent condition following stroke and other neurological conditions. Clinical assessment of spasticity relies predominantly on manual, non-instrumented, clinical scales. Technology based solutions have been developed in the last decades to offer more specific, sensitive and accurate alternatives but no consensus exists on these different approaches. METHOD: A systematic review of literature of technology-based methods aiming at the assessment of spasticity was performed. The approaches taken in the studies were classified based on the method used as well as their outcome measures. The psychometric properties and usability of the methods and outcome measures reported were evaluated. RESULTS: 124 studies were included in the analysis. 78 different outcome measures were identified, among which seven were used in more than 10 different studies each. The different methods rely on a wide range of different equipment (from robotic systems to simple goniometers) affecting their cost and usability. Studies equivalently applied to the lower and upper limbs (48% and 52%, respectively). A majority of studies applied to a stroke population (N = 79). More than half the papers did not report thoroughly the psychometric properties of the measures. Analysis identified that only 54 studies used measures specific to spasticity. Repeatability and discriminant validity were found to be of good quality in respectively 25 and 42 studies but were most often not evaluated (N = 95 and N = 78). Clinical validity was commonly assessed only against clinical scales (N = 33). Sensitivity of the measure was assessed in only three studies. CONCLUSION: The development of a large diversity of assessment approaches appears to be done at the expense of their careful evaluation. Still, among the well validated approaches, the ones based on manual stretching and measuring a muscle activity reaction and the ones leveraging controlled stretches while isolating the stretch-reflex torque component appear as the two promising practical alternatives to clinical scales. These methods should be further evaluated, including on their sensitivity, to fully inform on their potential.

Design of a Multi-Sensor System for Exploring the Relation between Finger Spasticity and Voluntary Movement in Patients with Stroke.

A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.