Lower Limb Spasticity Research Articles

Mobile digital gait analysis captures effects of botulinum toxin in hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) comprise a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness. Botulinum toxin has been approved for lower limb spasticity following stroke and cerebral palsy, but its effects in HSPs remain underexplored. We aimed to characterize the effects of botulinum toxin on clinical, gait, and patient-reported outcomes in HSP patients and explore the potential of mobile digital gait analysis to monitor treatment effects and predict treatment response. We conducted a prospective, observational, multicenter study involving ambulatory HSP patients treated with botulinum toxin tailored to individual goals. Comparing data at baseline, after 1 month, and after 3 months, treatment response was assessed using clinical parameters, goal attainment scaling, and mobile digital gait analysis. Machine learning algorithms were used for predicting individual goal attainment based on baseline parameters. A total of 56 patients were enrolled. Despite the heterogeneity of treatment goals and targeted muscles, botulinum toxin led to a significant improvement in specific clinical parameters and an improvement in specific gait characteristics, peaking at the 1-month and declining by the 3-month follow-up. Significant correlations were identified between gait parameters and clinical scores. With a mean balanced accuracy of 66%, machine learning algorithms identified important denominators to predict treatment response. Our study provides evidence supporting the beneficial effects of botulinum toxin in HSP when applied according to individual treatment goals. The use of mobile digital gait analysis and machine learning represents a novel approach for monitoring treatment effects and predicting treatment response.

Effects of dry needling on spasticity and motor function in paralympic athletes: a study protocol for a randomised controlled trial

No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity and motor...

Pain, disability, and quality of life in participants after concurrent onabotulinumtoxinA treatment of upper and lower limb spasticity: Observational results from the ASPIRE study.

Upper and lower limb spasticity is commonly associated with central nervous system disorders including stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and spinal cord injury, but little is known about the concurrent treatment of upper and lower limb spasticity with botulinum toxins. To evaluate onabotulinumtoxinA (onabotA) utilization and to determine if concurrent onabotA treatment of the upper and lower limbs has supported improvements in participants with spasticity. Sub-analysis of a 2-year, international, prospective, observational registry (ASPIRE, NCT01930786). International clinic sites (54). Adult spasticity participants across etiologies, who received ≥1 concurrent onabotA treatment of the upper and lower limbs during the study. Participants were treated with onabotA at the clinician's discretion. Baseline characteristics and outcomes of disability (Disability Assessment Scale [DAS]), pain (Numeric Pain Rating Scale [NPRS]), participant satisfaction, physician satisfaction, and quality of life (QoL; Spasticity Impact Assessment [SIA]) were evaluated. Adverse events were monitored throughout the study. Of 744 participants enrolled, 730 received ≥1 dose of onabotA; 275 participants received treatment with onabotA in both upper and lower limbs during ≥1 session; 39.3% of participants were naïve to onabotA for spasticity. The mean (SD) total dose per treatment session ranged from 421.2 (195.3) to 499.6 (188.6) U. The most common baseline upper limb presentation was clenched fist (n = 194, 70.5%); lower limb was equinovarus foot (n = 219, 66.9%). High physician and participant satisfaction and improvements in pain, disability and QoL were reported after most treatments. Nine participants (3.3%) reported nine treatment-related adverse events; two participants (0.7%) reported three serious treatment-related severe adverse events. No new safety signals were identified. More than a third of enrolled participants received at least one concurrent onabotA treatment of the upper and lower limbs, with reduced pain, disability, and improved QoL after treatment, consistent with the established safety profile of onabotA for the treatment of spasticity.

Assessment of pain relief after four botulinum toxin A injection cycles in patients with post-stroke lower limb spasticity: A prospective, observational study

IntroductionSpasticity is common after a stroke and is an independent risk factor for developing pain. BotulinumtoxinA injection is the treatment of choice for focal spasticity. We examined the effect of intramuscular botulinumtoxinA on pain relief in patients in routine clinical practice who were experiencing pain as a primary complaint associated with post-stroke lower limb spasticity. MethodsProspective, multicentre, post-marketing observational study. The study period was 16 months. The primary effectiveness variable was the mean change from baseline on the pain 0–10 Numerical Rating Scale after four botulinumtoxinA injection cycles. Secondary endpoints included changes from baseline on the pain 0–100 Visual Analogue Scale, Goal Attainment Scale, modified Ashworth Scale, 10-Meter Walk Test, Penn Spasm Frequency Scale, and 36-item Short-Form Health Survey. ResultsOf 186 enrolled patients, 180 (96.8%) received botulinumtoxinA at least once. The mean (standard deviation) pain 0–10 Numerical Rating Scale score decreased significantly (p<0.0001) from 4.9 (2.2) at baseline to 2.5 (2.1) at study end, representing a 50% decrease in pain severity. Relief of pain due to spasticity was supported by improvement from baseline in all secondary variables except the 10-Meter Walk Test. Two adverse events (erysipelas and phlebitis) in one patient were considered likely to be related to botulinumtoxinA injection. ConclusionBotulinumtoxinA appears to provide pain relief as an additional benefit of local treatment in patients with post-stroke lower limb spasticity for whom pain relief is a primary therapeutic goal (a Lay Abstract has been provided as Appendix A).

AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) comprises a large group of neurogenetic disorders characterized by progressive lower extremity spasticity. Neurological evaluation and genetic testing were completed in a Malian family with early-onset HSP. Three children with unaffected consanguineous parents presented with symptoms consistent with childhood-onset complicated HSP. Neurological evaluation found lower limb weakness, spasticity, dysarthria, seizures, and intellectual disability. Brain MRI showed corpus callosum thinning with cortical and spinal cord atrophy, and an EEG detected slow background in the index patient. Whole exome sequencing identified a homozygous missense variant in the adaptor protein (AP) complex 2 alpha-2 subunit (AP2A2) gene. Western blot analysis showed reduced levels of AP2A2 in patient-iPSC derived neuronal cells. Endocytosis of transferrin receptor (TfR) was decreased in patient-derived neurons. In addition, we observed increased axon initial segment length in patient-derived neurons. Xenopus tropicalis tadpoles with ap2a2 knockout showed cerebral edema and progressive seizures. Immunoprecipitation of the mutant human AP-2-appendage alpha-C construct showed defective binding to accessory proteins. We report AP2A2 as a novel genetic entity associated with HSP and provide functional data in patient-derived neuron cells and a frog model. These findings expand our understanding of the mechanism of HSP and improve the genetic diagnosis of this condition.

Turkish translation and transcultural validity and reliability of an assessment tool for spasticity: Leg Activity Measure (Leg A)

ABSTRACT Background The Leg Activity Measure is the only self-report measure that has been published to date that takes into account both the influence on quality of life and passive and active function in the literature. Aims The purpose is to examine the translation, cross-cultural adaptation validity and reliability of the Turkish version of the Leg Activity Measure (Tr-LegA). Methods Neurological patients (n = 52) with lower limb spasticity (aged 47.09 ± 14.74 years) were enrolled. The study consisted of two stages. At the first stage, the scale was translated into Turkish and culturally adapted. Validity and reliability analyses were conducted at the second stage. Construct validity was evaluated by exploratory factor analysis (EFA). The Rivermead Mobility Index (RMI), Nottingham Health Profile (NHP), and Functional Independence Measure (FIM) were used for convergent validity. The reproducibility (test-retest reliability) was assessed by the intraclass correlation coefficient (ICC). Furthermore, the standard error of measurement (SEM) was calculated. Results EFA suggested one factor for the Passive Function and two factors for the Active Function and Impact on Quality of Life Scales (QoL). Tr-LegA Passive and Active Function Scales were correlated with the total RMI, NHP, and FIM (p < 0.05). Tr-LegA Impact on Quality of Life Scale was correlated with the RMI and NHP (p < 0.05). Tr-LegA Passive Function Scale (ICC = 0.997), Tr-LegA Active Function Scale (ICC = 0.996), and Tr-LegA Impact on Quality of Life Scale (ICC = 0.976) had good reliability. Only Passive Function Scale had a significant floor effect (25%). Conclusions Tr-LegA is a valid and reliable multidimensional scale for passive and active function and quality of life in patients with lower limb spasticity. The clinical trial number NCT05182411.

KCNJ3 is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia identified using whole genome sequencing.

Hereditary spastic paraplegia (HSP) is a group of familial diseases characterized by progressive corticospinal tract degeneration. Clinically, patients present with lower-limb spasticity and weakness. To date, more than 80 genetic HSP types have been identified. Despite advances in molecular genetics, novel HSP gene discoveries are ongoing, with a low genetic diagnostic yield. In this study, we aimed to determine pathogenic variants in a family with HSP, which was not diagnosed through conventional genetic testing. We clinically characterized a large family and conducted whole genome sequencing (WGS) analysis of four affected and three unaffected individuals in the family to identify the genetic cause of HSP. This family had autosomal dominant pure (uncomplicated) late childhood-onset HSP. The patients' symptoms accelerated between the ages of 20 and 30. Brain magnetic resonance images typically showed white matter changes, a thin corpus callosum, and cerebellar atrophy. We identified a heterozygous missense variant, KCNJ3 c.1297T>G (p.Leu433Val), through WGS and family genetic analysis, confirmed by Sanger sequencing. We suggest that the identification of KCNJ3 c.1297T>G (p.Leu433Val) constitutes the discovery of a potential novel gene responsible for HSP in this family. This is the first study to report the possible role of a KCNJ3 variant in HSP pathogenesis. Our findings further expand the phenotypic and genotypic spectrum of HSP.

Effectiveness of AbobotulinumtoxinA in Adults with Lower Limb Spasticity: Top Line Results from the AboLiSh Observational Study (P7-11.020)

Effectiveness of AbobotulinumtoxinA in Adults with Lower Limb Spasticity: Top Line Results from the AboLiSh Observational Study (P7-11.020)

Leg Activity Measure (LegA) Sensitivity to Change Following Treatment of Lower Limb Spasticity with a Single Cycle of AbobotulinumtoxinA in an Ambulatory Population

Leg Activity Measure (LegA) Sensitivity to Change Following Treatment of Lower Limb Spasticity with a Single Cycle of AbobotulinumtoxinA in an Ambulatory Population

Most Frequently Injected Muscles for Lower Limb Spasticity in Routine Practice: AboLiSh Study Baseline Data

Most Frequently Injected Muscles for Lower Limb Spasticity in Routine Practice: AboLiSh Study Baseline Data

RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Effect on functional outcome of robotic assisted rehabilitation versus conventional rehabilitation in patients with complete spinal cord injury: a prospective comparative study.

Prospective Comparative Study. This study aims to compare the functional outcomes of Robotic-assisted rehabilitation by Lokomat system Vs. Conventional rehabilitation in participants with Dorsolumbar complete spinal cord injury (SCI). University level teaching hospital in a hilly state of northern India. 15 participants with Dorsolumbar SCI with ASIA A neurology were allocated to robotic rehabilitation and 15 participants to conventional rehabilitation after an operative procedure. Pre-and Post-rehabilitation parameters were noted in terms of ASIA Neurology, Motor and sensory function scores, WISCI II score (Walking Index in SCI score), LEMS (Lower Extremity Motor Score), SCI M III score (Spinal Cord Independence Measure III score), AO Spine PROST (AO Patient Reported Outcome Spine Trauma), McGill QOL score (Mc Gill Quality of Life score), VAS score (Visual Analogue Scale) for pain and Modified Ashworth scale for spasticity in lower limbs. On comparing robotic group with conventional group there was a statistically significant improvement in Robotic-assisted rehabilitation group in terms of Motor score (p = 0.034), WISCI II score (p = 0.0001), SCIM III score (p = 0.0001), AO PROST score (p = 0.0001), Mc GILL QOL score (p = 0.0001), Max velocity (p = 0.0001) and Step length (p = 0.0001). Whereas LEMS score (p = 0.052), ASIA neurology (p = 0.264 (ASIA A); 1.000 (ASIA B); 0.053 (ASIA C)), VAS score (p = 0.099), Sensory score (p = 0.422) and Modified Ashworth scale for spasticity (p = 0.136) were not statically significant when comparing between two groups. Robot-assisted rehabilitation is superior than conventional rehabilitation in people living with SCI with AIS A neurology. Differences in the patient group, type of a lesion its and severity, duration from onset to initiation of rehabilitation, devices employed, administration of the therapies and regulation of interventions are likely the cause of variations in the findings seen in the literature for robotic assisted training. III.

Tumefactive Multiple Sclerosis: A Mimicker of Intracranial Space-Occupying Lesions

Abstract: A chronic disease of CNS, Multiple sclerosis is characterized by inflammation and demyelination with axonal injury affecting upper motor neurons of brain or spinal cord. Tumefactive multiple sclerosis is a rare form of MS which mimics intracranial tumor-like space-occupying lesions on radiography. A 25-year old gentleman presented 2-month history of gradual onset difficulty in walking, slurring of speech and double vision. The patient had an ataxic gait accentuated by tandem walking with tendency to fall towards right and a negative Romberg’s sign. There was dysarthria and signs of cerebellar lesion present on the right side. Muscle tone was normal in upper limbs but increased (spasticity) in lower limbs bilaterally. Power was normal but deep tendon reflexes were exaggerated in all 4 limbs with bilateral up-going plantar reflex. MRI scan of the brain demonstrated tumour-like tumefactive lesions in the right cerebellum, right pons and the left subcortical region with no post-contrast enhancement of these lesions. MRI of whole spine demonstrated subtle hyperintense signals in the cervical spine. He had a past history of transverse myelitis 2 years ago with full clinical recovery with oral steroids. He was diagnosed with Tumefactive Multiple Sclerosis and started on corticosteroid therapy resulting in dramatic improvement.

(220) Sexual Dysfunction in Krabbe Disease Patients - A Scoping Review

Abstract Introduction Krabbe Disease (KD) or globoid cell leukodystrophy is a rare autosomal recessive lysosomal storage disorder affecting approximately 1 in 100,000 people worldwide. GALC gene mutations associated with KD involve a galactosylceramidase deficiency, which damages the oligodendrocytes and Schwann cells. Therefore, nervous system demyelination is a hallmark of KD. While only a few infants survive beyond two years in early-onset Krabbe disease, patients with late-onset Krabbe Disease exhibit a milder phenotype and longer life expectancy. Late-onset KD symptoms include progressive muscle weakness and stiffness, developmental regression, behavioral changes, dementia, hearing loss, vision problems, and seizures. Only a few cases of sexual dysfunction associated with KD have been reported in literature but they highlight the wide-ranging impact of this condition on young adults and adults. Objective This review aims to examine sexual dysfunction in KD, as reported in literature. We employ a broad definition of sexual dysfunction (erectile dysfunction, dyspareunia, orgasmic disorder, muscle weakness, etc.) and its incidence in both sexes with KD. A comprehensive review of this topic has not yet been conducted, and we offer here preliminary information for healthcare providers when addressing sexual concerns in patients with lysosomal storage disorders. Methods A literature search was conducted by two separate investigators who independently screened studies and abstracted data. Data sources included peer reviewed publications from the following databases: PubMed, Scopus, Web of Science, EMBASE, Cochrane, Google Scholar and Clinical trials.gov. There were no restrictions on language nor date of publication. The search algorithm utilized to generate the review list was: (Globoid cell leukodystrophy OR Galactosylcerebrosidase deficiency OR Galactosylceramidase deficiency OR Krabbe disease OR Late-onset Krabbe disease OR GALC mutation). Results were further filtered by article type, restricting articles to Case Reports, Clinical Trials, Reviews, and Systematic Reviews. Results were then screened for reports containing data on sexual dysfunction in patients with KD. Results A total of four case reports and one review paper contained reports of sexual dysfunction in KD patients. All cases involved late-onset Krabbe disease, characterized by a milder and more insidious presentation. Genitourinary symptoms reported included urinary incontinence (N=3) and erectile dysfunction (N=2), however, there were no reports (N=0) of symptoms related to female sexual dysfunction. Other symptoms commonly reported in late-onset KD that might be linked to sexual function were ataxia, spasticity and weakness of lower limbs (N=3), and sensory dysfunction due to peripheral neuropathy (N=4). Conclusions This pioneering review reveals that patients with KD experience symptoms of sexual dysfunction. While the rarity of KD makes it challenging to study it clinically, sexual dysfunction may be consistent with the known pathophysiology of late-onset KD. This review also highlights that sexual dysfunction in female patients with KD is an under-investigated component of the disease presentation. Future clinical research into this important comorbidity, especially in female patients where the literature is lacking, may improve the care of patients with KD. Disclosure No.

Postoperative pain and pain management following selective dorsal rhizotomy

BackgroundSelective dorsal rhizotomy (SDR) is a neurosurgical procedure that reduces lower limb spasticity, performed in some children with spastic diplegic cerebral palsy. Effective pain management after SDR is essential for...

Effectiveness of Extracorporeal Shock Wave Therapy in Treatment of Spasticity of Different Aetiologies: A Systematic Review and Meta-Analysis.

Background: Spasticity is a motor disorder characterised by exaggerated movements of the tendons and accompanied by hyperreflexia and hypertonia. Extracorporeal shock wave therapy (ESWT) is used as a treatment for spasticity, although more evidence is needed on the effectiveness of this therapy in the treatment of spasticity. Therefore, the aim of this study was to assess the effectiveness ESWT in the treatment of upper and lower limbs spasticity in both children and adults through different aetiologies. Methods: A systematic search was performed in different databases from inception to December 2023. Random-effects meta-analysis was used to estimate the efficacy of ESWT on spasticity using the Modified Ashworth Scale. Results: Sixteen studies were included in the systematic review and meta-analysis. The effect of ESWT on spasticity measured with the Modified Ashworth Scale shows a significant decrease in spasticity in the upper limbs and in the lower limbs in adults with chronic stroke and in children with cerebral palsy, is more effective immediately after application, and maintains its effect up to 12 weeks post treatment. Conclusions: These findings are important for clinical practice since they show evidence that ESWT is effective in reducing spasticity in both children and adults.

Assessment of spasticity-related pain in cerebral palsy and the efficacy of its treatment with incobotulinumtoxin A (literature review)

Pain in cerebral palsy (CP) occurs in 30–60% of cases. Pain associated with spasticity (PAS) is one of the most common causes of pain syndrome in cerebral palsy, which is often associated with impairment of the child’s daily life. Recently, more studies have been published on the use of botulinum toxin type A preparations to control PAS. The review article presents the results of a special pooled analysis of data on the analgesic effect of the drug Xeomin (incobotulinumtoxin A) in the treatment of PAS based on data from three phase III multicentre prospective comparative studies in children and adolescents with spastic forms of cerebral palsy. To evaluate PAS and the effect of incobotulinumtoxin A on it, a special questionnaire (Questionnaire on Pain caused by Spasticity, QPS) was used in these studies. The QPS reflects the child's pain associated with spasticity, which can be observed at rest and during various activities of the child.It was found that the children included in these studies reported the presence of PAS in more than 80% of cases with lower limb spasticity and in almost 70% of cases with upper limb spasticity. Parents or caregivers of these children observed an even higher prevalence of PAS. The use of incobotulinumtoxin A showed not only a pronounced antispastic effect, but also a significant reduction in the frequency and intensity of PAS in children and adolescents with cerebral palsy during normal daily activities, and during strenuous activities such as physical exercise and rehabilitation treatment. With repeated injection cycles of incobotulinumtoxin A, PAS continued to decrease, ensuring a reduction in pain even when physical activity became more difficult. Nowadays, injections with incobotulinumtoxin A can be considered as a routine therapeutic approach for the treatment of spasticity and increased muscle tone, but it is certainly an innovative method for effective pain reduction in cerebral palsy patients with lower and upper limb spasticity accompanied by PAS.

DDHD2, whose mutations cause spastic paraplegia type 54, enhances lipophagy via engaging ATG8 family proteins.

Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. One subtype of HSP, known as SPG54, is caused by biallelic mutations in the DDHD2 gene. The primary pathological feature observed in patients with SPG54 is the massive accumulation of lipid droplets (LDs) in the brain. However, the precise mechanisms and roles of DDHD2 in regulating lipid homeostasis are not yet fully understood. Through Affinity Purification-Mass Spectroscopy (AP-MS) analysis, we identify that DDHD2 interacts with multiple members of the ATG8 family proteins (LC3, GABARAPs), which play crucial roles in lipophagy. Mutational analysis reveals the presence of two authentic LIR motifs in DDHD2 protein that are essential for its binding to LC3/GABARAPs. We show that DDHD2 deficiency leads to LD accumulation, while enhanced DDHD2 expression reduces LD formation. The LC3/GABARAP-binding capacity of DDHD2 and the canonical autophagy pathwayboth contribute to its LD-eliminating activity. Moreover, DDHD2 enhances the colocalization between LC3B and LDs to promote lipophagy. LD·ATTEC, a small molecule that tethers LC3 to LDs to enhance their autophagic clearance, effectively counteracts DDHD2 deficiency-induced LD accumulation. These findings provide valuable insights into the regulatory roles of DDHD2 in LD catabolism and offer a potential therapeutic approach for treating SPG54 patients.

Cost-effectiveness of abobotulinumtoxinA plus best supportive care compared with best supportive care alone for early treatment of adult lower limb spasticity following an acute event.

Spasticity is an incurable chronic condition, and patients with spasticity frequently experience symptoms such as muscle stiffness, restricted mobility, fatigue, spasms, and pain. The study objective was to assess the cost-effectiveness of abobotulinumtoxinA plus best supportive care compared with best supportive care alone for the early treatment of adult lower limb spasticity following an acute event (e.g. stroke or traumatic brain injury), from an Australian payer perspective. Using clinical data from published pivotal trials, an economic model based on a Markov model was developed to capture changes in treatment costs, healthcare resource use costs, functional outcomes, and health-related quality of life over a lifetime horizon. Scenario analyses and a probabilistic sensitivity analysis were conducted to explore the uncertainty in the model parameters and assumptions used in the base case. AbobotulinumtoxinA plus best supportive care was cost-effective versus best supportive care, yielding an incremental cost-effectiveness ratio of $35,721 per quality-adjusted life year gained. Sensitivity analyses confirm the robustness of the base case, with most results remaining below the commonly acceptable cost-effectiveness willingness-to-pay threshold of $75,000 per quality-adjusted life year for cost-effectiveness in Australia. Inputs and assumptions that produced the top four highest incremental cost-effectiveness ratios include the application of different health resource utilisation source, short time horizon, unweighted regression analyses to determine regression probabilities, and no stopping rule. AbobotulinumtoxinA plus best supportive care has a 74% probability of being cost-effective compared with best supportive care alone at the willingness to pay threshold. AbobotulinumtoxinA plus best supportive care treatment is cost-effective in Australia for the management of adult lower limb spasticity in patients treated within 2 years of an acute event.

Advance of research on Hereditary spastic paraplegia type 4

Spastic paraplegia type 4 (SPG4) is the most common type of autosomally inherited spastic paraplegia. Its main clinical features include typical simple hereditary spastic paraplegia, with neurological impairments limited to lower limb spasticity, hypertonic bladder dysfunction, and mild weakening of lower limb vibration sensation, without accompanying features such as nerve atrophy, ataxia, cognitive impairment, seizures, and muscle tone disorders. SPAST is the main pathogenic gene underlying SPG4, and various pathogenic SPAST variants have been discovered. This disease has featured a high degree of clinical heterogeneity, and the same pathogenic variant can have different age of onset and severity among different patients and even within the same family. There is a lack of systematic research on the correlation between the genotype and phenotype of SPG4, and the pathogenic mechanism has remained controversial. This article has provided a review for the clinical characteristics, pathogenic gene characteristics, correlation between the genotype and phenotype, and pathogenic mechanism of this disease, with an aim to provide reference for its clinical diagnosis and treatment.