Neurological manifestations and clinical outcomes in pediatric Alexander disease: single-center cohort and identification of novel GFAP variants.

To study the effect of combined use the integrated of EMS and robotic NCI on the functioning of UL in post-stroke spastic paresis in the early recovery period of ischemic stroke (IS). A randomized controlled trial involved 120 patients in the early recovery period of IS with moderate to severe spastic paresis of UL, with an average age of 57.43±3.68 years. By simple randomization, the patients were divided into 4 groups of 30 people each, depending on the medical rehabilitation program (MR). All patients received a basic MR program: therapeutic gymnastics for 30 minutes; magnetic field therapy on the neck and collar area for 20 minutes; therapeutic massage for 20 minutes. The patients of the control group (GC) received only the basic program; The main group (MG) - interval complex multi-purpose EMS of the agonist muscles and antagonist muscles of the forearm in combination with the use of NCI with exoskeletons of both hands; comparison group 1 (CG-1) - training using a robotic NCI; comparison group 2 (CG-2) - EMS. The duration of the MR course is 2 weeks, daily, 5 days a week, 10 treatments for each factor. The effectiveness of MR was evaluated at three control points (T): after completion of 5 procedures (T1) and 10 procedures (T2), 3 months after completion of MR (T3). Assessment tools: Medical Research Committee Scale (MRCs), Modified Ashworth Scale (mAs), The Fugl-Meyer Assessment for upper extremity (FMA-UE), The Action Research Arm Test (ARAT). Patients with MG demonstrated significant (p<0.05) positive dynamics of recovery of UL function at the end of the MR course and after 3 months. The increase in muscle strength in MG and CG-1 averaged 0.77 and 0.59 points (p<0.05) in the distal muscle group, in CG-2 (0.24 points) and GC (0.21 points), p>0.05 compared with baseline values. Only patients with MG (+7.7 points) achieved a clinically significant difference (Δ) in FMA-UE-total at the end of MR, while patients with CG-1 achieved Δ=+4.9 points. In patients with GC and CG-2, the values of Δ according to FMA-UE-total were comparable (+2.3 and 2.6 points, respectively). According to the ARAT test, only MG patients also achieved a clinically significant difference (+6.2 points). Patients with CG-1 - Δ=+3.5 points. In patients with GC and CG-2, Δ values were comparable (+1.3 and 2.2 points, respectively). Ideomotor training with EMS in MR of impaired VC function in patients with IS, combining stimulation of visual, vestibular, and proprioceptive analyzers with training of cognitive functions, promotes regression of sensorimotor disorders of UL and restoration of manipulative activity.

Abstract An 8‐month‐old, female, entire Maine Coon cat initially presented with spastic monoparesis of the right hindlimb that progressed to generalised spastic paresis over the ensuing days. A clinical diagnosis of generalised tetanus prompted the initiation of intensive supportive care, including antibiotics, skeletal muscle relaxants, analgesics and diligent nursing care. The cat developed a hiatal hernia, megaoesophagus and aspiration pneumonia. To meet the cat's nutritional requirements and to mitigate potential complications associated with dysfunctional swallowing, a percutaneous endoscopic gastrostomy tube was placed. After 21 days of hospitalisation, the patient was discharged. It took approximately 17 months for complete recovery, according to the owners. This case demonstrates the use of a percutaneous endoscopic gastrostomy tube to meet the nutritional needs and bypass the dysfunctional oesophagus of a cat with the uncommon diagnosis of generalised tetanus.

Hyper-resistance to passive muscle stretch is a common, debilitating symptom of spastic paresis. Although straightforward to assess, hyper-resistance is caused by a complex interaction of altered tissue properties, stretch hyperreflexia, and involuntary background muscle activation. Identifying the contribution of each underlying component causing hyper-resistance is of great significance for designing treatments. The aim of this study was to investigate the components contributing to ankle plantarflexors' hyper-resistance in spastic cerebral palsy. We compared ankle biomechanical and reflex variables during ankle plantarflexor stretches at various velocities in 15 individuals with mild spastic cerebral palsy (GMFCS I, age range: 9-22 yr, 10 males) versus 15 age- and sex-matched typically developing controls. In addition, we evaluated associations between biomechanical and reflex variables. The cerebral palsy group had a median 9° lower maximum passive dorsiflexion range of motion at slow stretch velocity (P = 0.001), a 9° lower stretch reflex threshold (P < 0.01) with higher stretch reflex response magnitude (P ≤ 0.001) for both soleus and medial gastrocnemius muscles, and higher peak torques at fast stretch velocities (P < 0.01). When normalized to the maximum passive range of motion, stretch reflex thresholds were not different between groups. Although hyperreflexia directly contributed to hyper-resistance, normalized stretch reflexes did not occur earlier in the stretch in individuals with cerebral palsy compared with typically developing controls, suggesting a direct influence of muscle hypo-extensibility on hyperreflexia. Treatments for hypo-extensibility are urgently needed, more so than treatments to reduce hyperreflexia. [Clinical trial prospectively registered in the International Standard Randomized Controlled Trial registry (No. 69044459)]NEW & NOTEWORTHY The difference in stretch reflex threshold angles as a measure of hyperreflexia between mild spastic cerebral palsy and typically developing groups was lost when normalized to the passive range of motion. Yet, in the cerebral palsy group, low stretch reflex thresholds correlated with high peak torques during stretches at fast velocities.

This report describes a case of stretching-induced gastrocnemius muscle rupture in a patient with lower limb spastic paresis. To the best of our knowledge, this is the first reported case of such an injury in this patient population. After 6 mins of progressive stretching of the gastrocnemius muscle, the patient experienced localized pain at the medial gastrocnemius musculotendinous junction. Ultrasonography confirmed a partial rupture of the medial gastrocnemius. In addition to presenting this clinical case, we propose a potential treatment approach based on recent evidence-based physiotherapy methods.

Background. Spasticity is one of the most common manifestations of muscle tone disorders in children with neurological disorders, including cerebral palsy. The number of these disa-bling diseases is increasing every year. Rehabilitation is aimed at reducing the degree of motor disorders, increasing the functional activity of a child, reducing pain, facilitating childcare and preventing orthopedic complications. The purpose was to assess the effectiveness of baclofen in the comprehensive rehabilitation of children with motor disorders due to organic CNS lesions. Materials and methods. We monitored 136 children aged 4 to 18 years who had motor disorders due to organic CNS lesions. They were divided into 2 groups: group 1 (main) — 72 patients (52.94 %) who received baclofen for 3 months and rehabilitation measures and group 2 (controls) — 64 children (47.06 %) who received only rehabilitation measures. Results. Analysis of the drug effect on the level of muscle tone according to neurological status, motor activity according to standardized scales (the Gross Motor Function Classification System, the Manual Ability Classification System, assessment of muscle tone according to the Modified Ashworth Scale) and the overall effectiveness of comprehensive rehabilitation therapy (measurement of the range of movements in the limb joints using a goniometer) showed a significant improvement in the patients’ state. The results obtained after the use of baclofen in children with spastic paresis and paralysis due to organic lesions of the CNS allow us to believe that baclofen can be recommended for use in general clinical practice as a justified component of comprehensive therapy of patients with generalized severe muscle tone disorders. Conclusions. The obtained results confirm the feasibility of using baclofen as a component of pharmacological correction for spastic syndrome in childhood.

Reliability of the Five Step Assessment and Its Coefficients of Impairment in Spastic Paresis.

Bovine spastic paresis (BSP) is a progressive neuromuscular disease of unknown origin that causes persistent stiffness of the hind limbs. The symptoms are similar to those of human motor neuron diseases such as primary (PLS) or amyotrophic lateral sclerosis (ALS). BSP occurs worldwide in cattle production with an estimated prevalence of <1%. For Germany, this means that around 20,000 Holstein cattle are affected. BSP is generally considered a hereditary disease, but there is no prevention through breeding programs. As a result, BSP not only affects animal welfare but also leads to economic losses in milk and beef production. Here, we used transcriptomics to analyse the brainstem, spinal cord and affected gastrocnemius muscle tissue of eight animals affected by BSP and eight control animals from slaughterhouses to gain new insights into the molecular mechanisms underlying BSP. We found that the expression of several genes was significantly different in animals affected by BSP compared to control animals. Specific genes for inhibitory neurons were downregulated in the brainstems of the affected animals, namely CCK (cholecystokinin), NPY (neuropeptide Y), and SST (somatostatin). These inhibitory neurotransmitters influence cerebral movement control, among other processes. Furthermore, OOSP2 (oocyte secreted protein 2) was found to be significantly upregulated in the affected animals in all tissues. This expression could best be explained by the presence of T-follicular-helper cells which, through interleukin 21, can trigger a TH-2-dominated immune response and lead to autoimmune encephalitis. Further cases were sampled for confirmation and we detected cell infiltrates of activated microglia and T-cells in the brainstem using immunohistochemistry. Microglial foci were significantly more abundant in animals affected by BSP than control animals. We conclude that BSP is caused by an autoimmune reaction directed against inhibitory interneurons in the brainstem and is due to a combination of genetics and environmental influences. This may result in lost controlling influence on the upper motor neurons via extrapyramidal pathways and therefore triggers the specific symptoms of motor neuron disease.

Preoperative gait pattern as predictor of gait changes following selective dorsal rhizotomy.

The effect of foot deformities on the interplay of forces within the foot: An analysis of multi-segment foot joint moments in cerebral palsy.

Background/Objectives: “Hermes” is an ankle–foot orthosis (AFO) with negative stiffness designed to mechanically compensate the symptomatic increase in plantarflexion (PF) torque (i.e., ankle joint torque resistance to dorsiflexion, DF) in patients with spastic paresis. Methods: The effectiveness of “Hermes” was evaluated in twelve patients with chronic unilateral spastic paresis after stroke. Using a robotic ankle manipulator, stiffness at the ankle joint was assessed across three conditions: ankle without Hermes (A), ankle with Hermes applying no torque compensation (A+H0%), and ankle with Hermes tuned to compensate 100% of the patients’ ankle joint stiffness (A+H100%). Results: A significant reduction in PF torque was found with Hermes applying compensation (A+H100%) compared to the conditions without Hermes (A) and with Hermes applying no compensation (A+H0%). Furthermore, a significant reduction in positive dorsiflexion work was found with Hermes applying compensation (A+H100%) compared to the condition with Hermes applying no compensation (A+H0%). Hermes did not significantly contribute to additional PF torque or positive work when applying no compensation (A+H0%). Conclusions: The reductions in PF torque achieved with Hermes are comparable to those seen with repeated ankle stretching programs and ankle robot training. Thus, Hermes is expected to assist voluntary dorsiflexion and improve walking in patients with spastic paresis.

Spastic paresis, a frequent consequence of stroke, is characterized by both neurological and muscular alterations, leading to decreased muscle strength, increased passive muscle stiffness, and subsequently, diminished functional capacity. Although conventional rehabilitation programs are effective in enhancing muscle strength, they often fail to yield clinically significant improvements in functional capacities. Eccentric Training (ET) has shown promise in addressing the shortened muscle fascicle lengths and joint contractures commonly observed in stroke survivors. Despite the prevalence of contractures and rigidity in this population, the effects of ET on the structural and mechanical properties of muscles remain underexplored. This study aims to investigate the impact of ET on gait speed in sub-acute stroke patients compared to conventional therapy. Additionally, we aim to explore the effects of ET on the mechanical properties, structural characteristics, and neuromuscular parameters of the plantar flexors. A randomized controlled trial will be conducted, adhering to CONSORT guidelines, with participants assigned to either a Conventional Therapy Group or an Eccentric Training Group. Assessments will be conducted at baseline, and after ET intervention, encompassing clinical, biomechanical, and functional evaluations. This study seeks to provide empirical evidence on the efficacy of ET in improving motor outcomes in sub-acute stroke patients, thereby informing more effective rehabilitation strategies.

Post-comatose disorders of consciousness (DoC) represent persistent neurological conditions with limited therapeutic options and a poor prognosis. Recent works advocate for exploring the effects of psychedelics to enhance brain complexity in DoC and ameliorate their consciousness. We investigated sub-anesthetic concentration of the atypical psychedelic ketamine for treating post-comatose prolonged DoC through a double-blind, placebo-controlled, cross-over trial involving three adult patients. Incremental concentrations of intravenous ketamine and saline were administered, alongside continuous electroencephalogram (EEG) recording and assessments of conscious behaviors and spastic paresis. Brain complexity, measured by Lempel-Ziv complexity (LZC) and explainable consciousness indicator (ECI), revealed increased LZC during ketamine infusion but no change in ECI. Patients exhibited reduced spastic paresis and increased arousal as time spent with eyes open but no positive change in diagnosis. No adverse effects were noted. This study contributes to understanding the relationship between consciousness and brain complexity and suggests a potential therapeutic role for ketamine in DoC.

Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial.

Background: The comprehensive therapeutic program, Constraint-induced movement therapy (CIMT), focuses on functional training of the paretic upper limb and the transfer of acquired skills in daily life. Aim: The purpose of the survey was to map the current experience of therapists and patients with the therapeutic toolkit and home activity monitoring. Methods: The components of CIMT currently used, monitoring forms, barriers to provision, and motivations and subjectively perceived limitations for the use of technology in rehabilitation for activity monitoring were explored with the use of on-line surveys. Results: A total of 95 occupational therapists and physiotherapists and 91 patients participated in the survey. Czech therapists reported the most common perceived barriers that limit CIMT provision were as follows: low number of suitable patients, lack of knowledge of the method, increased administrative and time demands, or concerns about the high demands of the method for patients. The patients themselves are then limited in participating in the program due to its low accessibility or fear of the high difficulty of the exercise. As part of monitoring, patients complete a paper exercise diary (36%) or less frequently one on a computer (6.7%), but most often they do not track the results (40.4%). A total of 55% of patient respondents are motivated to share their results electronically with their therapist. Conclusions: According to the survey results, patients with spastic paresis of the upper limb after brain injury are motivated to participate in remote therapy and share results of home exercise remotely. The application of innovative approaches in CIMT and activity monitoring increases the availability of therapeutic interventions with potential cost reduction in clinical practice.

Spasticity is one of the current conditions in people with consequences of damage to the central nervous system and makes a significant contribution to the patient’s recovery process. The purpose of the study is to verify the phenomenon of “spasticity” and study the possibility of its objective diagnosis. To search for literature sources, the PubMed and E-library databases were used. Based on an analysis of available sources, there is reason to abandon the widespread use of the term “spasticity”, replacing it with “deforming spastic paresis”, which will cover various pathophysiological features and variants of this condition, and accordingly revise both diagnostic and therapeutic approaches to this condition. The phenomenon of deforming spastic paresis can manifest itself with varying degrees of severity and in different phases of movement, and for different muscles in different ways. Despite the active development of capabilities from instrumental research methods, there are currently no unified and universal algorithms for assessing deforming spastic paresis. The most adequate methods seem to be those that use robotic test movements for testing, which makes it possible to standardize the method and make it more convenient for specialist assessment.

Spasticity is a common feature in patients with disruptions in corticospinal pathways. However, the term is used ambiguously. Here, spasticity is defined as enhanced velocity-dependent stretch reflexes and placed within the context of deforming spastic paresis encompassing other forms of muscle overactivity. This scoping review aims at evaluating the clinimetric quality of clinical outcome assessments (COAs) for spasticity across different pathologies and to make recommendations for their use. A literature search was conducted to identify COAs used to assess spasticity. An international expert panel evaluated the measurement properties in the included COAs. Recommendations were based on the MDS-COA program methodology based on three criteria: if the COA was (1) applied to patients with spastic paresis, (2) used by others beyond the developers, and (3) determined to be reliable, valid, and sensitive to change in patients with spasticity. We identified 72 COAs of which 17 clinician-reported outcomes (ClinROs) and 6 patient-reported outcomes (PROs) were reviewed. The Tardieu Scale was the only ClinRO recommended for assessing spasticity. One ClinRO-Composite Spasticity Index-and two PROs-Spasticity 0-10 Numeric Rating Scale and 88-Item Multiple Sclerosis Spasticity Scale-were recommended with caveats. The Ashworth-derived COAs were excluded after evaluation due to their focus on muscle tone rather than spasticity, as defined in this review. The Tardieu Scale is recommended for assessing spasticity, and two PROs are recommended with caveats. Consistent terminology about the various types of muscle overactivity is necessary to facilitate their assessment and treatment. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spastic Paresis: A Treatable Movement Disorder.

Background: Canine degenerative myelopathy represents a progressive neurodegenerative disorder impacting the spinal cord. Initial clinical signs of canine degenerative myelopathy are typically observed in animals around 8 years of age. The clinical signs are characterized by general proprioceptive ataxia and spastic paresis of the pelvic limbs, with an irrepressible progression to flaccid paraplegia after 1 year of the appearance of the signs. Therefore, canine degenerative myelopathy is considered a differential diagnosis for medullary neoplasms, disc protrusion, and hip dysplasia, and since the clinical signs presented by the animals are similar in all these diseases, genetic testing plays an important role in diagnosis. In several dog breeds degenerative myelopathy was linked to the c.118G&gt;A autosomal recessive variant in exon 2 of the superoxide dismutase 1 (SOD1) gene (SOD1:c.118G&gt;A). In addition, the SOD1:c.118G&gt;A variant in more than 124 breed dogs, suggesting that this variant is widely spread and fixed in the species before the breeds’ origin. However, there are few studies evaluating this variant in brazilian dogs, and none of them have evaluated it in the Brazilian Golden Retriever dogs. Therefore, this study aimed to evaluate the allele frequency of the SOD1:c.118G&gt;A variant in Golden Retriever dogs from Brazilian kennels. Materials, Methods &amp; Results: A total of 122 Brazilian Golden Retriever DNA samples were used in a PCR procedures with specific primers, previously described, to amplify a 779 base pairs amplicon containing the SOD1:c.118G&gt;A variant in this study. a non-template control reaction was performed to check possible contamination in the PCR preparation. The genotyping of the animals was performed by direct Sanger sequencing of PCR products that amplified a fragment containing the variant. Considering the 95% confidence interval, the sample size used in the present study was slightly larger than the minimum required to assess the allele frequency of SOD1:c.118G&gt;A variant (122 versus 113 samples). All animals assessed in this study were clinically normal at the time of sampling and were identified as wild-type for the SOD1:c.118G&gt;A variant. Therefore, no alleles of the pathogenic variant (A) were found in the studied population. Discussion: Although all animals assessed in this study were classified as wild-type, this study is the 1st report in Brazil to evaluate the prevalence of this variant in Golden Retriever dogs. The poor prognosis and inexorable progression of canine degenerative myelopathy force most owners to opt for early euthanasia of affected animals. Knowledge of the disease by owners and breeders, as well as the genotyping of their animals, may prevent the spread of the variant among lineages and also assist veterinarians in differential diagnosis and management of cases of canine degenerative myelopathy. The genetics of Brazilian Golden Retriever were mainly derived from USA bloodlines. With this in mind, we may speculate that the results observed in this study may be influenced by the lower prevalence of the SOD1:c.118G&gt;A variant previously found in American Golden Retrievers. The results obtained in the present study, combined with previous studies that described the occurrence of this variant as rare in Golden Retrievers, lead us to speculate that this variant does not impact the Brazilian Golden Retriever dogs. Keywords: dogs, canine degenerative myelopathy (CDM), neurodegenerative disease, genotyping, SOD1, variants.

Functional correlates of spastic myopathy, the muscle disorder of spastic paresis, are unknown. To explore reciprocal relationships between clinical and structural parameters of plantar flexors with i) ambulation speed, ii) dorsiflexion and plantarflexion torques in chronic hemiparesis. Cross-sectional trial in chronic stroke-induced hemiparesis (>6 months). Plantar flexors were quantified through i) the Five Step Assessment: maximal extensibility (XV1), active range of dorsiflexion (XA); ii) ultrasonography: fascicle length (Lf) and thickness (Th) of medial gastrocnemius (GAS) and soleus (SOL), knee extended in an isokinetic ergometer, ankle at 80% XV1-GAS. Maximal isometric torques in plantar flexion (PF) and dorsiflexion (DF) and maximal barefoot 10-meter ambulation speed were collected. Relationships between structural, biomechanical, clinical and functional parameters were explored using non-parametric testing (Spearman). Twenty-one subjects (age 58.0±8.4, mean±SD, time since lesion 7.8±5.7 years) were recruited, with the following characteristics: ambulation speed, 0.77±0.37m/sec; XV1-SOL 92.7±10.3°; XV1-GAS 91.3±9.6°; XA-SOL 86.9±10.0°; XA-GAS 7676±14.2°; LfGAS, 58.2±18.3mm; ThGAS, 17.1±3.6 mm; LfSOL, 36.0±9.6 mm; ThSOL, 13.8±3.3mm; PF peak-torque 46.5±34.1Nm, DF peak-torque, 20.1±19.1Nm. XA-SOL and XA-GAS strongly correlated with XV1-SOL and XV1-GAS respectively (ρ = 0.74, p = 4E-04; resp ρ = 0.60, p = 0.0052). Ambulation speed moderately correlated with LfGAS (ρ = 0.51, p = 0.054), ThGAS (ρ = 0.58, p = 0.02) and LfSOL (ρ = 0.63, p = 0.009). DF and PF peak-torques both correlated with LfGAS (ρ = 0.53, p = 0.04) a; resp. ρ = 0.71, p = 0.0015). In chronic hemiparesis, active dorsiflexion is mostly determined by plantar flexor extensibility. Plantar flexor fascicle shortening is associated with reduced ambulation speed and ankle torques. Attempts to restore plantar flexor extensibility might be important objectives for gait rehabilitation in chronic hemiparesis.