Overview of botulinum toxin as a treatment for spasticity in stroke patients

Spasticity after the occurrence of stroke induces limb deformity, functional disability and/or pain in patients, which limits their activities of daily living and deteriorates their quality of life. Botulinum toxin (BTX) has recently been reported as an efficacious therapeutic agent for the treatment of spasticity. Systematic review and meta-analysis studies have demonstrated that BTX therapy after stroke reduces spasticity and increases physical activity capacity and performance levels. Moreover, BTX can be used as an adjuvant in physiotherapy. Several studies have confirmed that the combination of BTX therapy and physiotherapy improves motor recovery. However, to date, only a few such combination studies have been conducted and their findings are considered preliminary and controversial. Therefore, future studies are required to determine the appropriate combination of treatment methods that will aid motor recovery.     

Intrathecal baclofen in multiple sclerosis: too little, too late?

The majority of patients with multiple sclerosis (MS) have symptoms of spasticity that increasingly impair function as the disease progresses. With appropriate treatment, however, quality of life can be improved. Oral antispasticity medications are useful in managing mild spasticity but are frequently ineffective in controlling moderate to severe spasticity, because patients often cannot tolerate the adverse effects of increasing doses. Intrathecal baclofen (ITB) therapy can be an effective alternative to oral medications in patients who have a suboptimal response to oral medications or who cannot tolerate dose escalation or multidrug oral regimens. ITB therapy may be underutilized in the MS population because clinicians (a) are more focused on disease-modifying therapies rather than symptom control, (b) underestimate the impact of spasticity on quality of life, and (c) have concerns about the cost and safety of ITB therapy. Delivery of ITB therapy requires expertly trained staff and proper facilities for pump management. This article summarizes the findings and recommendations of an expert panel on the use of ITB therapy in the MS population and the role of the physician and comprehensive care team in patient selection, screening, and management.     

What's the "catch" in upper-limb post-stroke spasticity: expanding the role of botulinum toxin applications

More than a third of stroke patients will develop post-stroke spasticity, especially involving the paretic upper limbs. Despite established, intensive rehabilitation programmes in place, spasticity may still affect a post-stroke patient's quality of life and create economic and caregiver burdens. Hence, there is a need to explore how botulinum toxin (BTX) therapy may further improve patient outcomes. Consensus guidelines on the clinical use of BTX for established and symptomatic upper-limb spasticity are now available. While BTX therapy has been universally shown to reduce muscle tone in spasticity, its corresponding improvement in functional-outcome measures are far from consistent. This review article attempts to analyse the reasons for the inconsistency and makes the case that improved and reliable functional outcomes after BTX therapy may be achieved when: patient-specific goals that incorporate realistic expectations (such as improving passive as well as active functions and reducing pain) are used as functional-outcome measures; patients are followed up over a reasonable amount of time so as to optimise learning, rehabilitation and possibly even allow plasticity to occur; and, correct and thoughtful muscle targeting that considers various factors, such as spread, technique and avoidance of compensatory muscles, is employed. This article also summarises the characteristics of post-stroke patients who are at greatest risk for developing spasticity and those who are most likely to become the "best responders;" and, it attempts to outline the potential advantages of early BTX therapy in the acute to sub-acute post-stroke period, while spasticity is still evolving.     

Symptomatic therapy and neurorehabilitation in multiple sclerosis

Multiple sclerosis (MS) is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and handicap. Symptoms that contribute to loss of independence and restrictions in social activities lead to continuing decline in quality of life. Our aim is to give an updated overview on the management of symptoms and rehabilitation measures in MS. Appropriate use of these treatment options might help to reduce long-term consequences of MS in daily life. First, we review treatment of the main symptoms of MS: fatigue, bladder and bowel disturbances, sexual dysfunction, cognitive and affective disorders, and spasticity. Even though these symptomatic therapies have benefits, their use is limited by possible side-effects. Moreover, many common disabling symptoms, such as weakness, are not amenable to drug treatment. However, neurorehabilitation has been shown to ease the burden of these symptoms by improving self-performance and independence. Second, we discuss comprehensive multidisciplinary rehabilitation and specific treatment options. Even though rehabilitation has no direct influence on disease progression, studies to date have shown that this type of intervention improves personal activities and ability to participate in social activities, thereby improving quality of life. Treatment should be adapted depending on: the individual patient's needs, demands of their surrounding environment, type and degree of disability, and treatment goals. Improvement commonly persists for several months beyond the treatment period, mostly as a result of reconditioning and adaptation and appropriate use of medical and social support at home. These findings suggest that quality of life is determined by disability and handicap more than by functional deficits and disease progression.     

A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients.

OBJECTIVE: To confirm the apparent effectiveness of botulinum toxin (BTX) in hemiparetic patients with ankle plantar flexors and foot invertor spasticity. METHODS: Twenty three hemiparetic patients with spasticity of the ankle plantar flexors and foot invertors were included in a randomised double blind, placebo controlled study with BTX. Patients were examined on days 0, 30, 90, and 120 and received one injection of BTX and one of placebo in a random order at day 0 and day 90. RESULTS: Patients reported a clear subjective improvement in foot spasticity after BTX (P = 0.0014) but not after placebo. Significant changes were noted in Ashworth scale values for ankle extensors (P < 0.0001) and invertors (P = 0.0002), and for active ankle dorsiflexion (P = 0.0001). Gait velocity was slightly but not significantly (P = 0.0731) improved after BTX injections. The severity of spasticity did not modify treatment efficacy, but BTX was less effective in patients with longer duration of spasticity (P = 0.0081). CONCLUSION: The efficacy of BTX injections in the treatment of spastic foot suggests that BTX may be particularly useful during the first year after a stroke.     

Neues zur symptomatischen MS‑Therapie: Teil 2 – Gangstörung und Spastik

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN?MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of gait disorders and spasticity will be discussed.     

Potential control of multiple sclerosis by cannabis and the endocannabinoid system

For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.     

Prevalence and treatment of spasticity reported by multiple sclerosis patients

The objective of this study was to characterize the population of multiple sclerosis (MS) patients suffering from spasticity and to evaluate treatment patterns, including intrathecal baclofen (ITB) delivery, related to patient quality of life (QOL). We conducted a cross-sectional, two-level study using data from the Patient Registry of the North American Research Committee on MS (NARCOMS). In addition, we surveyed a subgroup of 198 preselected patients who are using ITB (ITBG) and a random sample of 315 oral drug users (ORALG). Among the registrants, 16% reported no spasticity, 31% minimal, 19% mild, 17% moderate (frequently affects activities), 13% severe (daily forced to modify activities) and 4% total (prevents daily activities). Patients experiencing greater severity included by proportion males, and those older and with longer duration of MS. QOL scores decreased inversely with severity. In the focused survey, ITBG reported lower levels of spasticity than ORALG, less stiffness in the legs, less pain and fewer spasms at any time. They scored significantly lower in the SF-36 physical component, yet reported less fatigue on the MFIS scale. Prevalence data reveal that one third of MS patients modify or eliminate daily activities as a result of spasticity. Treatment of spasticity can significantly impact QOL parameters by reducing spasms, pain and fatigue.     

Evidence-based approach of the use of Botulinum toxin type A (BTX) in cerebral palsy

A systematic review with the Sachett model of evidence-based medicine of the use of Botulinum toxin type A (BTX) for intervention in children with Cerebral Palsy (CP) is highlighted. Currently, the evidence showed that BTX is useful for treating pes equinus due to spasticity of the gastrocnemius-soleus muscles. However, careful patient selection and goals of treatment have to be addressed. More multi-centre clinical trials with standardized protocols are needed before widespread recommendation of the use of BTX in treating spasticity in CP can be made.     

Managing specific symptoms in people with multiple sclerosis

Besides immunomodulation and immunosuppression, symptomatic treatment is an important part of MS therapy. Its goals are the elimination and reduction of symptoms that impair functional ability and quality of life, and also the avoidance of secondary complications. There are many treatment recommendations for MS symptoms, therefore clear and consensually developed therapeutic strategies are needed. This paper reviews some recommendations for the treatment of MS-related spasticity, fatigue, pain and neurogenic bladder dysfunction that have been established by the Multiple Sclerosis Treatment Consensus Group of the German MS Society.     

Update on HIV Dementia and HIV-Associated Neurocognitive Disorders

Botulinum toxin (BT) is a neurotoxin that paralyzes muscles by inhibiting release of acetylcholine from presynaptic vesicles at the neuromuscular junction. In people with multiple sclerosis (MS), clinical experience and research studies show that local injection of minute quantities of BT can temporarily control skeletal muscle spasticity, bladder detrusor hyperreflexia, and tremor. Specifically, BT injections have been shown to reduce muscle tone and improve passive function, and possibly improve active function, in patients with spasticity. Injection of BT into the bladder wall is a uniquely effective, safe, and durable treatment in patients with neurogenic detrusor hyperreflexia due to MS who have insufficient response or who do not tolerate oral antimuscarinic medications. This procedure has markedly reduced the need for indwelling catheters and bladder surgery. In addition, a recent study suggests BT may be effective for select patients with MS-associated upper extremity tremor. Appropriate use of BT can improve quality of life for many patients with MS.     

THC and CBD oromucosal spray (Sativex®) in the management of spasticity associated with multiple sclerosis

People with multiple sclerosis may present with a wide range of disease symptoms during the evolution of the disease; among these, spasticity can have a marked impact on their well-being and quality of life. Symptom control, including spasticity, remains a key management strategy to improve the patient's well-being and functional status. However, available drug therapies for spasticity sometimes have limited benefit and they are often associated with poor tolerability. Sativex is a 1:1 mix of 9-delta-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with multiple sclerosis is accumulating steadily. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status when Sativex was added to the current treatment regimen. Adverse events such as dizziness, diarrhea, fatigue, nausea, headache and somnolence occur quite frequently with Sativex, but they are generally of mild-to-moderate intensity and their incidence can be markedly reduced by gradual 'uptitration'. In summary, initial well-controlled studies with Sativex oromucosal spray administered as an add-on to usual therapy have produced promising results and highlight encouraging avenues for future research.     

Spasticity and everyday life in multiple sclerosis

Spasticity is one of the most commonly seen symptoms in patients with multiple sclerosis. However, evaluation of the symptom often uses clinical scales that do not incorporate its impact on activities of daily living and quality of life. The everyday life of patients is affected primarily in actions related to mobility and walking capacity, such as the use of transport, gardening, household activities and, ultimately, basic activities such as bathing and dressing. Yet, so far, no study has described the impact of spasticity on the daily life of patients with multiple sclerosis. Nevertheless, assessing the effects of spasticity on such a young population would appear to be essential for meeting the needs of these patients with appropriate therapeutic interventions.     

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

Purpose of Review

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.

Recent Findings

We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms.

Summary

Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

     

Management of pain in multiple sclerosis: a pharmacological approach

About half of patients with multiple sclerosis (MS) report pain; treatment for pain alone accounts for nearly 30% of the total use of medications for the management of all MS-related symptoms. Patients with MS can experience more than one type of pain simultaneously and at any point during the disease course, even in newly or recently diagnosed cases. Pain in MS can be associated with other symptoms, including spasticity, fatigue and mood disorder. Pain sufferers experience disruption in daily life activities, work, mood, recreation and general enjoyment of life, and report low satisfaction with pain management. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. The majority of clinical evidence regarding treatment stems from small pilot and open-label studies; therefore, treatment of pain associated with MS is often based on anecdotal reports and clinicians' experience. The open-label design of the majority of studies, the unavailability of large samples and the difficulty of performing placebo-controlled studies because of ethical considerations result in insufficient evidence to support or refute the effectiveness of pain medications. This Review presents available data regarding pharmacological approaches for addressing pain in MS and highlights the shortcomings in pain management research.     

选择性闭孔神经切断术治疗脑瘫性大腿内收肌群痉挛

目的 探讨选择性闭孔神经分支部分切断术治疗脑瘫患者大腿内收肌群痉挛状态的效果。方法 回顾分析2005年1月至2006年7月采用选择性闭孔神经分支部分切断术治疗的38例脑瘫性大腿内收肌群痉挛状态患者的临床资料。结果 全部病人平均随访7个月。100％的病人术后立即感大腿内收肌群痉挛状态缓解，随访期间缓解率为100％，运动功能改善率为78．9％（30／38）．生活质量提高率92．1％（35／38）。术后无下肢感觉障碍发生；出现大腿内收肌无力49侧，随访期间均见好转。痉挛状态无复发。结论 选择性闭孔神经分支部分切断术是治疗脑瘫性大腿内收肌群痉挛状态安全有效的显微外科手术方法。     

Transcranial magnetic stimulation primes the effects of exercise therapy in multiple sclerosis

Exercise therapy (ET) can be beneficial in disabled multiple sclerosis (MS) patients. Intermittent transcranial magnetic theta burst stimulation (iTBS) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS. We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients. In a double-blind, sham-controlled trial, 30 participants were randomized to three different interventions: iTBS plus ET, sham stimulation plus ET, and iTBS alone. Before and after 2 weeks of treatment, measures of spasticity through the modified Ashworth scale (MAS) and the 88 items Multiple Sclerosis Spasticity Score questionnaire (MSSS-88), fatigue through the Fatigue Severity Scale (FSS), daily living activities (ADL) through the Barthel index and health-related quality of life (HRQoL) through the 54 items Multiple Sclerosis Quality of life inventory (MSQoL-54) were collected. iTBS plus ET reduced MAS, MSSS-88, FSS scores, while in the Barthel index and MSQoL-54, physical composite scores were increased. iTBS alone caused a reduction of the MAS score, while none of the measured scales showed significant changes after sham iTBS plus ET. iTBS associated with ET is a promising tool for motor rehabilitation of MS patients.     

Cautious Use of Intrathecal Baclofen in Walking Spastic Patients: Results on Long‐term Follow‐up

Intrathecal baclofen is presently the most effective treatment for diffuse spasticity whatever the cause. The fact that both spasticity is always accompanied by a degree of muscle weakness and that any antispastic treatment causes a decrease in muscle strength indicate that major attention must be paid in treating spasticity in ambulant patients. Methods. We present here a retrospective study, approved by the insitutional ethics committee, of 22 ambulant spastic patients, selected as homogeneous for disease and disease duration, who were treated with intrathecal baclofen at the Istituto Nazionale Neurologico “C.Besta” in Milan. These patients were followed‐up for to 15 years of treatment and their clinical assessment was enriched by the evaluation of their functional independence measurement (FIM) before and during treatment. Results. There was improvement in quality of life as measured by the FIM scale; however, an increase in the patient's motor performance could not be detected. Conclusion. Although we did not show any improvement in muscle performance, intrathecal baclofen did improve daily quality of life, even in spastic patients who were able to walk.     

Botulinum toxin type A for the treatment of the upper limb spasticity after stroke: a meta-analysis

Muscle over-activity is one of the cardinal features of spasticity and it is a common disability of stroke patients. In this group, spasticity is responsible for several limitations that interfere in their daily activities and quality of life. To treat spasticity, neurologists usually prescribe drugs as baclofen, tizanidine or benzodiazepines or even use definitive treatment as phenol or surgery. Authors suggest the use of botulinum toxin type A (BTX-A) for spasticity in the upper limbs after stroke, but there are few papers with adequate methodology supporting this idea. In this article we summarize the data of previous double-blind, randomised clinical trials to asses, with a meta-analysis, if BTX-A is an adequate treatment for spasticity due to stroke. The results show a statistical superiority of BTX-A ov%r placebo on reducing muscle tone by the Modified Ashworth Scale (WMD= 0.95 [0.74 to 1.17]) in patients with post-stroke upper limb spasticity.     

Inclusion Body Myositis

Pain is a common symptom in multiple sclerosis (MS) and has recently been estimated to be experienced by up to 75 % of patients. Pain can be present at any point in the course of the disease and patients may experience pain from various causes simultaneously. Pain in MS can also be secondary to other symptoms, such as spasticity, fatigue, and mood disorder. Of all drug use to treat MS symptoms, treatment for pain accounts for nearly 30 % of total use. At the same time, patients report low satisfaction with pain management. Pain affects quality of life and can influence a person’s participation in family life and work and affect mood. Most of the pain literature in the field of MS is based on open-label studies involving small numbers of subjects. Placebo-controlled trials in severe pain syndromes such as trigeminal neuralgia are unethical but for other types of MS-related pain conditions, placebo-controlled trials are ethical and necessary to establish efficacy, particularly given the well-documented placebo effect for various painful conditions This review discusses available data and emphasizes areas of pain research that require further attention