Spastic Disorders Research Articles

Importance of Coping Strategies on Quality of Life in People with Multiple Sclerosis: A Systematic Review.

Multiple sclerosis (MS) is a neurodegenerative disorder of the central nervous system characterized by a variety of symptoms such as fatigue, spasticity, tremors, and cognitive disorders. Individuals with MS may employ different coping strategies to manage these symptoms, which in turn can significantly impact their quality of life (QoL). This review aims to analyze these coping strategies and their impact on QoL. Furthermore, it seeks to identify the key factors that influence the choice and effectiveness of these coping strategies, providing insights into which strategies are most beneficial for enhancing QoL in people with MS. Methods: Systematic searches were performed in Scopus, PubMed, Web of Science, and Scopus databases. This systematic review has been registered in OSF with the number DOI 10.17605/OSF.IO/QY37X. Results: A total of 1192 studies were identified. After reading the full text of the selected studies and applying predefined inclusion criteria, 19 studies were included based on their pertinence and relevance to the topic. The results revealed that emotional variables, demographic factors, personality traits, and family support significantly influence the choice of coping strategies used to manage the symptoms of MS. Problem-solving and task-oriented coping were prevalent among MS patients and associated with better QoL outcomes. Emotional-focused and avoidance strategies were generally linked to poorer QoL, though avoidance provided temporary relief in certain contexts. Social support, emotional health, and cognitive reframing were crucial in enhancing QoL. Conclusions: The findings underscore the importance of tailored psychoeducational and therapeutic interventions focusing on emotional health, social support, and adaptive coping strategies. These interventions can significantly improve the long-term outcomes for individuals with MS. Future research should explore the dynamic interactions between coping strategies and QoL over time, providing a comprehensive understanding of how to best support MS patients in managing their disease.

Urinary disorders in patients diagnosed with organic brain pathology

Introduction. This study is relevant due to the high prevalence of organic brain pathology and the negative influence of urination disorders on the quality of life.Objective. To analyse the impaired function of lower urinary tracts in patients with organic brain pathology.Materials & methods. We analysed 607 patients with severe organic brain pathology (105 had traumatic spinal cord injury (TSCI) and 457 had consequences of acute stroke (AS)). We performed clinical urological examinations. During the survey, attention was paid to the presence of urinary tract pathology at the examining time and anamnesis. Structural changes in the urinary tract were objectively assessed. We objectively assessed structural changes in urinary tracts including prostate adenoma in men, insufficiency of pelvic floor muscles in women and strictures of the urethra or ureters. The degree of the spastic syndrome was assessed with the Ashworth Scale. The neurourological examination included cystometry with the measurement of bladder volume and post-void residual urine. The cognitive status of the patients was assessed with the MMSE (Mini-Mental State Examination) questionnaire. The correlation analysis between the degree of spastic syndrome measured with the Ashworth Scale and urination disorders was performed with Spearman rank correlation.Results. All patients had neurogenic dysfunction of the lower urinary tract. A combination of bladder retention and emptying disorders was found in 62 men older than 45yo with benign prostate hyperplasia (10,2% of all cases). An impaired accumulation function in history was found in 45 women older than 45yo (7,4% of all observations). The level of spasticity was 3 or 4 points on the Ashworth Scale in patients with TSCI and 2 to 4 points in those with AS. The analysis of correlations between the degree of spasticity and urination disorders showed a moderate relationship (r = 0,4) in patients with TSCI and a medium relationship (r = 0.65) in patients with AS.Conclusion. Neurogenic dysfunction of the lower urinary tract accompanies patients with severe organic brain pathology throughout their life and requires adequate correction.

Esophageal Per-Oral Endoscopic Myotomy (E-POEM): Future Directions and Perspectives.

POEM is a mature procedure endorsed by societal guidelines as a first line therapy for achalasia and spastic esophageal disorders. Nonetheless, several questions remain, including expanding indications for POEM, periprocedural evaluation and management, and the optimal POEM technique to enhance clinical success while mitigating risk for reflux. There is uncertainty regarding several technical aspects of the POEM myotomy; though aggregating evidence supports the use of real-time impedance planimetry to guide the myotomy. While post-POEM reflux remains a concerning long term sequela, there is an increasing focus on the potential role of endoscopic anti-reflux interventions. Lastly, with the widespread adoption of POEM, we continue to witness ongoing efforts to standardize post-procedural care and training in this procedure. POEM is no longer a novel but rather established procedure. Yet, this technique has continued to evolve, with the aim of optimizing treatment success while reducing adverse events and risk for post-procedural reflux.

Levator Labii Superioris Alaeque Nasi Targeted Botulinum Toxin Injection for Treatment of Perinasal Facial Discomfort and Snarling.

Botulinum toxin has been increasingly studied and used for varying conditions, most notably, cosmetics. However, it has been shown that botulinum toxin demonstrates a high efficacy in treating spasticity disorders throughout the body, including the face. Facial spasms vary in pathophysiology, region, and severity. Some can be so severe that they can cause discomfort and emotional distress due to the involuntary facial expressions caused by the spasms. Most spasticity conditions are often treated with adjuvant therapy of oral muscle relaxants and analgesics depending on severity. However, these treatments impose risks of varying adverse effects from sedation, hypotension, and if chronic use, more severe effects such as central nervous system complications or QT prolongation. In addition, if spasms are localized, the muscle relaxant's mechanism is not targeted, leading to unnecessary systemic use. That being said, a more targeted and manageable treatment such as botulinum toxin presents itself as a potential option for patient's physical condition and everyday life quality. Our case presents a 62-year-old male, with a chronic history of localized, idiopathic spasms and discomfort within the Levator Labii Superioris Aqulae Nasi region. The patient had no history of previous neurological disorders, and imaging was unremarkable. The patient had been treated over the past 13 years with varying oral therapeutics including Cymbalta, Ibuprofen, and cyclobenzaprine with limited improvement, but presented to the clinic seeking a different treatment plan, as the adverse effects from the muscle relaxants were impeding his everyday activities. The patient was also experiencing significant pain and emotional stress due to the spasms. The risk and benefits of treatment options were discussed and the patient decided to move forward with botulinum injections. After the first injection, the patient reported his pain had significantly improved and was relieved to be off of chronic pain medications. Our case demonstrates, what increasing literature further also supports: botulinum toxin is becoming a potential effective treatment for a breadth of spasticity disorders with a more targeted mechanism, and more manageable treatment plan, while simultaneously improving the patient's quality of life.

Identification and analyses of exonic and copy number variants in spastic paraplegia

Hereditary spastic paraplegias are a diverse group of degenerative disorders that are clinically categorized as isolated; with involvement of lower limb spasticity, or symptomatic, where spastic paraplegia is complicated by further neurological features. We sought to identify the underlying genetic causes of these disorders in the participating patients. Three consanguineous families with multiple affected members were identified by visiting special schools in the Punjab Province. DNA was extracted from blood samples of the participants. Exome sequencing was performed for selected patients from the three families, and the data were filtered to identify rare homozygous variants. ExomeDepth was used for the delineation of the copy number variants. All patients had varying degrees of intellectual disabilities, poor speech development, spasticity, a wide-based gait or an inability to walk and hypertonia. In family RDHR07, a homozygous deletion involving multiple exons and introns of SPG11 (NC000015.9:g.44894055_449028del) was found and correlated with the phenotype of the patients who had spasticity and other complex movement disorders, but not those who exhibited ataxic or indeterminate symptoms as well. In families ANMD03 and RDFA06, a nonsense variant, c.985C > T;(p.Arg329Ter) in DDHD2 and a frameshift insertion‒deletion variant of AP4B1, c.965-967delACTinsC;p.(Tyr322SerfsTer14), were identified which were homozygous in the patients while the obligate carriers in the respective pedigrees were heterozygous. All variants were ultra-rare with none, or very few carriers identified in the public databases. The three loss of function variants are likely to cause nonsense-mediated decay of the respective transcripts. Our research adds to the genetic variability associated with the SPG11 and AP4B1 variants and emphasizes the genetic heterogeneity of hereditary spastic paraplegia.

Cannabis use by individuals with spinal cord injury in the UK: a call for improved patient education and physician awareness for pain and spasticity management

Study designProspective observational qualitative study.ObjectiveCannabis is used by patients for the treatment of chronic pain, spasticity, sleep issues or mood disorders such as anxiety and depression. Since 2018, it has been authorised in the United Kingdom for medical use as an unlicensed medicine. This study aims to determine if patients are using cannabis for the management of symptoms related to spinal cord injury, and if so, whether they are using medical or illicit cannabis.MethodsSpinal cord injury patients from the Yorkshire Regional Spinal Injuries Centre and SPINE Community in the United Kingdom were surveyed. Participants were sent a 7-point electronic survey. All results were anonymous, and confidentiality was maintained throughout the process.ResultsIn total, 223 patients completed the survey. Not all patients answered every question. Of those who responded 65.35% (n = 132) were paraplegic and 34.65% (n = 70) were tetraplegic. Patients were suffering from chronic pain (longer than 3 months), spasticity, loss of/difficulty in sleeping or anxiety/depression. Almost 15% (14.93%, n = 33 out of 221) used cannabis to manage their symptoms, out of those the majority used street cannabis (79.41%, n = 27 out of 34) were using street cannabis.ConclusionThis study demonstrates that there are spinal cord injury patients in the UK using cannabis to treat their symptoms. A majority appear to be using illicit cannabis. Given that cannabis can interact with other medications, and that the quality and content of illicit cannabis can be highly variable and at times dangerous, it is important for physicians to discuss cannabis use with their patients. This can inform prescribing and allow them to educate patients on the dangers of medical cannabis and potential alternatives.

Neurosurgical treatment of spasticity: a potential return to the cerebellum.

Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders. In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity. Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity. Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.

Discriminating "impaired" from "disordered" contractile response on FLIP panometry by utilizing pressure measurement.

Functional lumen imaging probe (FLIP) panometry evaluates esophageal motility, including the contractile response to distension, that is, secondary peristalsis. Impaired/disordered contractile response (IDCR) is an abnormal, but nonspecific contractile response that can represent either hypomotility or spastic motor disorders on high-resolution manometry (HRM). We hypothesized that FLIP pressure could be incorporated to clarify IDCR and aimed to determine its utility in a cohort of symptomatic esophageal motility patients. 173 adult patients that had IDCR on FLIP panometry and HRM with a conclusive Chicago Classification v4.0 (CCv4.0) diagnosis were included and analyzed as development (n = 118) and validation (n = 55) cohorts. FLIP pressure values were assessed for prediction of either hypomotility or spasm, defined on HRM/CCv4.0. HRM/CCv4.0 diagnoses were normal motility in 48 patients (28%), "hypomotility" (ineffective esophageal motility, absent contractility, or Type I or II achalasia) in 89 (51%), and "spasm" (Type III achalasia, distal esophageal spasm, or hypercontractile esophagus) in 36 (21%). The pressure at esophagogastric junction-distensibility index (DI) (60 mL) was lower in hypomotility (median [interquartile range] 34 [28-42] mmHg) than in spasm (49 [40-62] mmHg; p < 0.001) and had an area under the receiver operating characteristic curve of 0.80 (95% CI 0.73-0.88) for hypomotility and 0.76 (0.69-0.83) for spasm. For "spasm" on HRM, a threshold FLIP pressure of >35 mmHg provided 90% sensitivity (47% specificity) while >55 mmHg provided 93% specificity (40% sensitivity). Pressure on FLIP panometry can help clarify the significance of IDCR, with low-pressure IDCR associated with hypomotility and high-pressure IDCR suggestive of spastic motor disorders.

Clinical outcome analysis of patients with multiple sclerosis – Analysis from the UK Medical Cannabis Registry

IntroductionWhilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR). MethodPatients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant. Results141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %). ConclusionsThis preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design.

Botulinum toxin: a new differential diagnosis for a lytic bone lesion

BackgroundBotulinum toxin, produced by the Gram-positive anaerobe Clostridium botulinum, is composed of seven antigenic subtypes (A, B, C, D, E, F, and G). Currently, only Botulinum toxin type A, commonly referred to as “Botox,” is approved for clinical use, given its relatively safe clinical profile. Botulinum toxin type A has a wide range of therapeutic indications, including treatment for dystonia, migraine headache, neurogenic bladder, and large muscle spastic disorders. However, the toxin is most widely known for its cosmetic effects in treating wrinkles and facial lines.Case presentationThis article describes a 62-year-old Caucasian female who presented for investigation and workup of an isolated lytic lesion of her frontal bone a few weeks after administration of botulinum toxin injection into the corresponding site in the frontalis muscle. This presented as a large, palpable, painless forehead lump causing significant psychological distress. After no neoplastic cause for the lesion was found and histopathology was performed, our researchers concluded that the most likely explanation was that the bony lytic lesion resulted from inadvertent injection of the “Botox” neurotoxin through the intended target muscle and into the cortex of the underlying bone.ConclusionsOur search of the literature failed to identify any previous cases of this occurring. However, as the popularity of this cosmetic procedure only increases, we believe that this represents an important possible differential for isolated lytic lesion after administration of “Botox” injection.

Racial and Ethnic Disparities in the Medical Management of Poststroke Complications Among Patients With Acute Stroke.

To inform clinical practice, we sought to identify racial and ethnic differences in the medical management of common poststroke complications. A cohort of acutely hospitalized, first-time non-Hispanic White (NHW), non-Hispanic Black, and Hispanic patients with stroke was identified from electronic medical records of 51 large health care organizations (January 1, 2003 to December 5, 2022). Matched propensity scores were used to account for baseline differences. Primary outcomes included receipt of medication(s) associated with the management of the following poststroke complications: arousal/fatigue, spasticity, mood, sleep, neurogenic bladder, neurogenic bowel, and seizure. Differences were measured at 14, 90, and 365 days. Subgroup analyses included differences restricted to patients with ischemic stroke, younger age (<65 years), and stratified by decade (2003-2012 and 2013-2022). Before matching, the final cohort consisted of 348 286 patients with first-time stroke. Matching resulted in 63 722 non-Hispanic Black-NHW pairs and 24 009 Hispanic-NHW pairs. Non-Hispanic Black (versus NHW) patients were significantly less likely to be treated for all poststroke complications, with differences largest for arousal/fatigue (relative risk (RR), 0.58 [95% CI, 0.54-0.62]), spasticity (RR, 0.64 [95% CI, 0.0.62-0.67]), and mood disorders (RR, 0.72 [95% CI, 0.70-0.74]) at 14 days. Hispanic-NHW differences were similar, albeit with smaller magnitudes, with the largest differences present for spasticity (RR, 0.67 [95% CI, 0.63-0.72]), arousal/fatigue (RR, 0.77 [95% CI, 0.70-0.85]), and mood disorders (RR, 0.79 [95% CI, 0.77-0.82]). Subgroup analyses revealed similar patterns for ischemic stroke and patients aged <65 years. Disparities for the current decade remained significant but with smaller magnitudes compared with the prior decade. There are significant racial and ethnic disparities in the treatment of poststroke complications. The differences were greatest at 14 days, outlining the importance of early identification and management.

Correlation between Improved Balance and Decreased Limb Spasticity and Improved Muscle Strength in Post-Stroke Hemiparesis

Approximately 80% of stroke patients experience disability in the form of hemiparesis (weakness of half of the body). Physiotherapy problems that commonly occur in post-stroke hemiparesis include decreased muscle strength, spasticity, and balance disorders. This research is a correlation analysis study with one independent variable and 2 dependent variables, aiming to determine the correlation between balance improvement with decreased leg muscle spasticity and improved leg muscle strength in post-stroke hemiparesis patients, carried out at the Inggit Medical Center Clinic Makassar with a total sample of 12 people who met the inclusion criteria and were given intervention in the form of the bobath method for 10 treatments, the measuring instruments used were functional reach test (FRT) for balance, Asworth scale for spasticity, and chair stand for leg muscle strength. Spearman test between balance and muscle strength obtained a p value of 0.001 (p &lt;0.05) with a positive r of 0.822 which means there is a positive and significant correlation between increasing balance and increasing muscle strength. While between balance and spasticity obtained a p value of 0.04 (p &lt;0.05) with a negative r value of 0.584, which means there is a negative and significant correlation between increasing balance and decreasing spasticity. Improved balance has a significant relationship with increased muscle strength, and improved balance has a significant relationship with decreased spasticity in post-stroke hemiparesis patients.

Peroral endoscopic myotomy for spastic esophageal dysmotility among opioid users: a multicenter propensity score matching study

Opioid-induced esophageal dysfunction (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). The aim of this study was to evaluate and compare clinical outcomes of peroral endoscopic myotomy (POEM) for SEDs and EGJOO among opioid users and nonusers. This propensity score (PS) matching study included consecutive opioid users and nonusers who underwent POEM for SEDs and EGJOO between January 2018 and September 2022. The following covariates were used for the PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as a post-POEM Eckardt score≤3. A total of 277 consecutive patients underwent POEM during the study period. PS matching resulted in the selection of 64 pairs of patients strictly matched 1:1 (n= 128) with no statistically significant differences in demographic, baseline, or procedural characteristics or in the parameters considered for the PS between the 2 groups. Clinical response to POEM was significantly lower among opioid users (51 of 64 [79.7%]) versus nonusers (60 of 64 [93.8%]) (P= .03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood of failure to respond to POEM (odds ratio, 4.59; 95% confidence interval, 1.31-3.98; P= .02). Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users versus nonusers. There was a dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.

The Use of Botulinum Toxin-A Injection in Medicine and Orthopaedic Surgery

Study Design: Literature Review Background: Botulinum toxin A (BTX-A) targets specific muscle groups to block the release of acetylcholine at the neuromuscular junction and, therefore, reduce muscular activation. Through weaking of muscle activity, BTX-A injections have become widely used for cosmetic purposes, as well as the treatment of various neuromuscular disorders including strabismus, movement disorders, and overactive bladder syndrome. Objective: To review the history of BTX-A injections, as well as discuss its current and future cosmetic, medical, and surgical applications. Methods: A comprehensive literature review was performed on the development, application, and efficacy of BTX-A injections in the treatment of various neuromuscular and spinal disorders. Results: Within the orthopaedic spine world, BTX-A injections have effectively been utilized for the treatment of spastic muscular disorders, including spinal cord injuries, cervical spine pain, lower back pain, and scoliosis. By reducing muscular tone, BTX-A injections have shown over 90% reduction in pain after repeated injections. Conclusions: BTX-A is an essential neurotoxin that functions not only through cosmetic application, but also in the treatment of neuromuscular and spinal disorders. Further studies of greater sample size are needed to fully address potential limitations and assess long-term success of such treatment modalities.

Diagnosis and Management of Esophageal Motility Disorders Beyond Achalasia

Abstract High-resolution esophageal manometry (HREM) is the gold standard for the diagnosis of esophageal motility disorders. Achalasia cardia has been the most extensively studied esophageal motility disorder. However, nonachalasia esophageal motility disorders are common too. The present review highlights the diagnosis and management strategies for these disorders. HREM needs to be complemented with clinical symptoms and timed barium esophagogram/functional lumen imaging probe to properly diagnose spastic and hypomotility disorders. Use of Indian normative values is essential to identify patients with these motility disorders accurately. Adjunctive tests such as multiple rapid swallows and rapid drink challenge increase the diagnostic accuracy of HREM studies. HREM is mainly useful in reflux patients with refractory symptoms and for preoperative assessment. Its role in postsurgical cases is evolving.

Anesthesia choice and its potential impact on endoluminal functional lumen imaging probe measurements in esophageal motility disorders

The widespread use of peroral endoscopic myotomy (POEM) has revolutionized the management of esophageal motility disorders (EMDs). The introduction of an endoluminal functional lumen imaging probe (EndoFLIP, Medtronic, Dublin, Ireland) can serve as a complementary diagnostic tool to assess the mechanical properties (ie, pressure, diameter, distensibility, topography) of the esophagus. During EndoFLIP measurements, different anesthesia techniques may induce variable degrees of neuromuscular blockade, potentially affecting esophageal motility and altering the results of EndoFLIP metrics. The aim of this study was to compare the impact of using total intravenous anesthesia (TIVA) versus general anesthesia with inhalational anesthetics (GAIA) on diagnostic EndoFLIP measurements. This retrospective study included all adult patients (≥18 years) undergoing EndoFlip during the POEM procedure at our institution between February 2017 and February 2022. Differences in pressure, diameter, and distensibility index were obtained by using propofol-based TIVA versus sevoflurane-based GAIA with a 30 mL and a 60 mL balloon. The differences were divided into terciles and compared between diagnoses by using univariate comparisons and logistic regression models. A total of 49 patients were included (39% type I achalasia, 43% type II or III achalasia, and 18% jackhammer esophagus [JE]). Compared with spastic disorders (types II and III achalasia and JE), type I had lower values of pressure differences at 60 mL in univariate (3.75 vs 15.20, P= .001) and multivariate (adjusted odds ratio, .89; 95% confidence interval, .82-.978) analyses. Compared with type I, types II and III achalasia had higher rates of pressure differences at 60 mL in the univariate (9.85 vs 3.75, P= .04) analysis and nearly reached significance in the multivariate analysis (1.09; 95% confidence interval, 1-1.20). Compared with type I achalasia, JE exhibited higher values in pressure differences at 60 mL (27.7 vs 3.75, P< .001). Esophageal pressure, as measured by EndoFLIP, was significantly reduced when patients were sedated with sevoflurane-based GAIA. The use of sevoflurane-based GAIA for diagnostic EndoFLIP may potentially lead to the misclassification of spastic disorders as type I achalasia. Propofol-based TIVA should therefore be considered over sevoflurane-based GAIA for sedation during the diagnostic test.

Beyond neuromuscular activity: botulinum toxin type A exerts direct central action on spinal control of movement

Overt muscle activity and impaired spinal locomotor control hampering coordinated movement is a hallmark of spasticity and movement disorders like dystonia. While botulinum toxin A (BoNT-A) standard therapy alleviates mentioned symptoms presumably due to its peripheral neuromuscular actions alone, the aim of present study was to examine for the first time the toxin's trans-synaptic activity within central circuits that govern the skilled movement. The rat hindlimb motor pools were targeted by BoNT-A intrasciatic bilateral injection (2 U per nerve), while its trans-synaptic action on premotor inputs was blocked by intrathecal BoNT-A–neutralising antitoxin (5 i.u.). Effects of BoNT-A on coordinated and high intensity motor tasks (rotarod, beamwalk swimming), and localised muscle weakness (digit abduction, gait ability) were followed until their substantial recovery by day 56 post BoNT-A. Later, (day 62–77) the BoNT-A effects were examined in unilateral calf muscle spasm evoked by tetanus toxin (TeNT, 1.5 ng). In comparison to peripheral effect alone, combined peripheral and central trans-synaptic BoNT-A action induced a more prominent and longer impairment of different motor tasks, as well as the localised muscle weakness. After near-complete recovery of motor functions, the BoNT-A maintained the ability to reduce the experimental calf spasm evoked by tetanus toxin (TeNT 1.5 ng, day 62) without altering the monosynaptic reflex excitability. These results indicate that, in addition to muscle terminals, BoNT-A-mediated control of hyperactive muscle activity in movement disorders and spasticity may involve the spinal premotor inputs and central circuits participating in the skilled locomotor performance.

Improvement of the treatment of patients with spastic movement disorder after stroke

Spastic movement disorder (SMD) develops in up to 43% of cases as a sequela of stroke. In the event of afunctionally relevant or daily life impairing SMD or to avoid an impending complication, the medicinal treatment of afocal, multifocal and segmental increase in muscle tone with botulinum neurotoxinA (BoNT-A) is recommended; however, treatment data reveal alack of guideline-conform treatment with BoNT‑A in Germany. The aim of the reported expert meeting was to discuss solutions to the incorrect treatment and undertreatment of patients with SMD and to formulate consensus recommendations to improve the care situation. At aconsensus meeting held in April 2022, eight experts from the fields of neurology, physical medicine and rehabilitation discussed the causes for the incorrect treatment and undertreatment and formulated consensus solution approaches. Possible reasons for the current incorrect treatment and undertreatment in SMD management in Germany include insufficient awareness of SMD among physicians, alack of treatment capacities, alack of information transfer in discharge management as well as staff shortages in the specialized inpatient and outpatient SMD treatment centers. The committee therefore recommended apatient pathway in which affected patients with SMD are provided with correctly implemented BoNT‑A treatment in combination with physical measures. The recommended treatment pathway for use in stroke patients is intended to close gaps in care and thus ensure guideline-conform treatment of post-stroke SMD.

Refinement of intrathecal catheter design to enhance neuraxial distribution

BackgroundDelivery of therapeutics via indwelling intrathecal catheters is highly efficacious for targeting of pain, spasticity, neuraxial cancer and neurodegenerative disorders. However, current catheter designs have some major limitations. Given limited CSF flow, fixed intrathecal volume and the large distance of the rostro-caudal spinal axis, current intrathecal delivery routes fail to achieve adequate drug distribution. Additionally open catheter systems are plagued with cellular ingrowth and debris accumulation if used intermittently. New method1.We addressed these issues by designing a new catheter that includes micro-valves2.Micro-valves distributed along the catheter open simultaneously upon adequate local transmural pressure, which is evenly distributed along the catheter fluid column.3.Buildup of transmural pressure, prior to microvalve opening, results in increased solute exit velocity.4.Micro-valves are closed when not in use, preventing anything from entering the system, and allowing for long-term intermittent use. Results/comparison with existing method(s)High speed imaging showed micro-valve catheters greatly increase fluid exit velocities compared to typical open-ended catheters, which prevents pooling of injectate proximal to the opening. When implanted intrathecally in rats, small injection volumes (7.5 μL) of dye or AAV9-RFP, resulted in an even rostro-caudal distribution along the spinal axis and robust transfection of neurons from cervical to lumbar dorsal root ganglia. In contrast, such injections with an open-ended catheter resulted in localized distribution and transfection proximal to the delivery site.Our poly micro-valve catheter design resulted in equivalent transfection rates of cervical DRG neurons using 100x lower titer of AAV9-RFP. Unlike open port catheters, no debris accumulation was observed in the lumen of implanted catheters, showing potential for long-term intermittent use. ConclusionsThis catheter platform, suitable for small animal models is easily scalable for human use and addresses many of the problems observed with common catheter systems.

Post-Stroke Spastic Movement Disorder and Botulinum Toxin A Therapy: Early Detection And Early Injection.

Post-stroke spastic movement disorder (PS-SMD) develops in up to 40% of stroke survivors after a first ever stroke within the first year. Chronic PS-SMD is often associated with severe disabilities and complications, emphasizing the importance of its early recognition and early adequate management. Extensive research has aimed to accurately predict and sensitively detect a PS-SMD. Symptomatic therapies include conventional rehabilitation and local intramuscular injections of botulinum toxin A (BoNT-A). The latter is widely used, but primarily in the chronic phase of stroke. However, recent studies have shown the safety and efficacy of BoNT-A therapy even in the acute phase and early sub-acute phase after stroke, i.e., within three months post-stroke, leading to an improved long-term outcome in stroke rehabilitation. Local BoNT-A injections evolve as the primary approach in focal, multifocal, and segmental chronic or acute/subacute PS-SMD. Patients at high risk for or manifest PS-SMD should be identified by an early spasticity risk assessment. By doing so, PS-SMD can be integral part of the patient-centered goal-setting process of a multiprofessional spasticity-experienced team. The benefit of an early PS-SMD treatment by BoNT-A should predominate putative degenerative muscle changes due to long-term BoNT-A therapy by far. This, as early treatment effectively avoids complications typically associated with a PS-SMD, i.e., contractures, pain, skin lesions. The management of PS-SMD requires a comprehensive and multidisciplinary approach. Early assessment, patient-centered goal setting, early intervention, and early use of BoNT-A therapy prevents from PS-SMD complications and may improve rehabilitation outcome after stroke.