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Objective: This randomised, double blind, placebo controlled, two parallel group study was conducted to assess the beneficial effect of injection of botulinum toxin A (Dysport) into the subscapularis muscle on shoulder pain in stroke patients with spastic hemiplegia. Methods: A single dose of botulinum toxin A (500 Speywood units) or placebo was injected into the subcapularis muscle. Pain was assessed using a 10 point verbal scale. Subscapularis spasticity was assessed by the change in passive shoulder lateral rotation and abduction. Upper limb spasticity was assessed using the Modified Ashworth Scale for shoulder medial rotators, and elbow, wrist and finger flexors. Assessments were carried out at baseline and at weeks 1, 2 and 4. Results: Twenty patients (10 patients per group), 11 with ischaemic stroke and 9 with haemorrhagic stroke, completed the study. Pain improvement with botulinum toxin A was observed from week 1; score difference from baseline at week 4 was 4 points versus 1 point with placebo (p = 0.025). Lateral rotation was also improved, with a statistically significant difference compared with placebo at week 2 (p = 0.05) and week 4 (p = 0.018). A general improvement in upper limb spasticity was observed; it was significant for finger flexors at week 4 (p = 0.025). Conclusions: Subscapularis injection of botulinum toxin A appears to be of value in the management of shoulder pain in spastic hemiplegic patients. The results confirm the role of spasticity in post-stroke shoulder pain.

Background: Spasticity is defined/assessed in resting limbs, where increased stretch reflex activity and mechanical joint resistance are evident. Treatment with antispastic agents assumes that these features contribute to the movement disorder, although it is unclear whether they persist during voluntary contraction. Objectives: To compare reflex amplitude and joint resistance in spastic and normal limbs over an equivalent range of background contraction. Methods: Thirteen normal and eight hemiparetic subjects with mild/moderate spasticity and without significant contracture were studied. Reflex and passive joint resistance were compared at rest and during six small increments of biceps voluntary contraction, up to 15% of normal maximum. A novel approach was used to match contraction levels between groups. Results: Reflex amplitude and joint mechanical resistance were linearly related to contraction in both groups. The slopes of these relations were not above normal in the spastic subjects on linear regression. Thus, reflex amplitude and joint resistance were not different between groups over a comparable range of contraction levels. Spastic subjects exhibited a smaller range of reflex modulation than normals because of decreased maximal contraction levels (weakness) and significant increases of resting contraction levels. Conclusions: Spasticity was most evident at rest because subjects could not reduce background contraction to normal. When background contractions were matched to normal levels, no evidence of exaggerated reflex activity or mechanical resistance was found. Instead, reduced capacity to modulate reflex activity dynamically over the normal range may contribute to the movement disorder. This finding does not support the routine use of antispastic agents to treat the movement disorder.

Objective: To study the efficacy, safety, and incidence of BtxA antibody formation with repeated treatments with BtxA in post-stroke upper limb muscle spasticity. Methods: The study was a prospective open label trial. Patients with established post-stroke upper limb spasticity received 1000 units of BtxA (Dysport) into five muscles of the affected arm on study entry. Treatment was repeated every 12, 16, or 20 weeks as clinically indicated. Each patient received a total of three treatment cycles. Efficacy of treatment was assessed using the Modified Ashworth Scale. Patients were assessed on study entry and on week 4 and 12 of each treatment cycle for all safety and efficacy parameters. Blood samples for BtxA antibody assay were taken at baseline and on completion of the trial. Results: Fifty one patients were recruited and 41 of them completed the study. Improvement from the cycle one baseline was observed in all the outcome measures. Mild to moderately severe treatment related adverse events were reported in 24% of cases. There were no serious adverse events. No BtxA antibodies were detected. Conclusion: BtxA at a dose of 1000 units Dysport was efficacious in the symptomatic treatment of post-stroke upper limb spasticity. The study suggests that this effect can be maintained with repeated injections for up to at least three treatment cycles, with duration of effect per cycle of between 12 and 20 weeks. BtxA was safe in the dose used in this study and did not induce the formation of detectable levels of neutralising BtxA antibodies.

Background: Spasticity and loss of function in an affected arm are common after stroke. Although botulinum toxin is used to reduce spasticity, its functional benefits are less easily demonstrated. This paper reports an exploratory meta-analysis to investigate the relationship between reduced arm spasticity and improved arm function. Method: Individual data from stroke patients in two randomised controlled trials of intra-muscular botulinum toxin were pooled. The Modified Ashworth Scale (elbow, wrist, fingers) was used to calculate a "Composite Spasticity Index". Data from the arm section of the Barthel Activities of Daily Living Index (dressing, grooming, and feeding) and three subjective measures (putting arm through sleeve, cleaning palm, cutting fingernails) were summed to give a "Composite Functional Index". Change scores and the time of maximum change were also calculated. Results: Maximum changes in both composite measures occurred concurrently in 47 patients. In 26 patients the improvement in spasticity preceded the improvement in function with 18 showing the reverse. There was a definite relationship between the maximum change in spasticity and the maximum change in arm function, independent of treatment (ρ = –0.2822, p = 0.0008, n = 137). There was a clear relationship between the changes in spasticity and in arm function in patients treated with botulinum toxin (Dysport) at 500 or 1000 units (ρ = –0.5679, p = 0.0090, n = 22; ρ = –0.4430, p = 0.0018, n = 47), but not in those treated with placebo or 1500 units. Conclusions: Using a targeted meta-analytic approach, it is possible to demonstrate that reducing spasticity in the arm is associated with a significant improvement in arm function.

Objectives: This study was conducted to evaluate the long term clinical and electrophysiological outcome by recording the H reflex in a consecutive series of six patients treated by selective tibial neurotomy for spastic equinus foot. Method: The amplitudes of Hmax reflexes, Mmax responses, and Hmax:Mmax ratio were recorded in six patients with chronic lower limb spasticity, before and after surgery, at day 1 and 8 months and 24 months after selective tibial neurotomy. The passive range of movement, the stretch reflex score according to the Tardieu scale, the osteoarticular and tendon repercussions, and the quality of motor control of dorsiflexion were evaluated preoperatively and postoperatively. Results: At the end of the study, all patients presented a reduction of equines. Gait and Tardieu's score of spasticity had improved in all patients. Active dorsiflexion of the ankle was unchanged in four patients, but two improved by 5° to 12°. In five cases, fascicular resection of the superior nerve to soleus was, alone, sufficient to reduce spastic equinus foot, without recurrence, for a mean follow up of 28 months. Two patients were reoperated on, one for remaining spasticity related to an underestimated spasticity of the gastrocnemius muscles, and the other for painful claw toes. Hmax, Mmax, and Hmax:Mmax ratios were significantly lower the day after surgery. The reduction of Hmax and Hmax/Mmax ratio remained stable over time and was still statistically significant two years after the operation. However, the value of Mmax eight months postoperatively was no longer significantly different from the preoperative value. Conclusion: This study shows the long term efficacy of the selective tibial neurotomy as treatment of spastic equinus foot. Neurotomy confined to fibres supplying the soleus muscle is sufficient in most cases and acts by decreasing sensory afferents without significant long term motor denervation.

To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study.In total, 630 patients with stable MS with muscle spasticity from 33 UK centres were randomised to receive oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabis extract, or placebo in the main 15 week CAMS study. The primary outcome was change in the Ashworth spasticity scale. Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK Neurological Disability Score, postal Barthel Index, General Health Questionnaire-30, and a series of nine category rating scales. Following the main study, patients were invited to continue medication, double blinded, for up to 12 months in the follow up study reported here.Intention to treat analysis of data from the 80% of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months (Delta(9)-THC mean reduction 1.82 (n = 154, 95% confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n = 172, 95% CI -0.99 to 1.19), placebo -0.23 (n = 176, 95% CI -1.41 to 0.94); p = 0.04 unadjusted for ambulatory status and centre, p = 0.01 adjusted). There was suggestive evidence for treatment effects of Delta(9)-THC on some aspects of disability. There were no major safety concerns. Overall, patients felt that these drugs were helpful in treating their disease.These data provide limited evidence for a longer term treatment effect of cannabinoids. A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS.

Objectives: To evaluate long term change in impairment, disability, and health related functional status in patients with severe spasticity who received intrathecal baclofen. Methods: A long term (more than five years) observational longitudinal follow up study assessing 21 patients who received intrathecal baclofen given by programmable pump. Patients had chronic disabling spasticity which did not respond to oral antispasmolytic agents. Clinical efficacy was assessed by the Ashworth scale and spasm score; disability by the expanded disability status scale (EDSS), ambulation index (AI), and incapacity status scale (ISS); and health related quality of life by the sickness impact profile (SIP) and the Hopkins symptom checklist (HSCL). Results: Compared with pretreatment values, there was a significant improvement in clinical efficacy (Ashworth scale and spasm score, p

Background: Hereditary spastic paraparesis (HSP) denotes a group of inherited neurological disorders with progressive lower limb spasticity as their clinical hallmark; a large proportion of autosomal dominant HSP belongs to HSP type 4, which has been linked to the SPG4 locus on chromosome 2. A variety of mutations have been identified within the SPG4 gene product, spastin. Objective: Correlation of genotype and electrophysiological phenotype. Material: Two large families with HSP linked to the SPG4 locus with a very similar disease with respect to age of onset, progression, and severity of symptoms. Methods: Mutation analysis was performed by PCR from genomic DNA and cDNA, and direct sequencing. The motor system was evaluated using transcranial magnetic stimulation. Results: Patients differ in several categories depending on the type of mutation present. Conclusions: For the first time in hereditary spastic paraparesis, a phenotypic correlate of a given genetic change in the spastin gene has been shown.

Objective: To quantify velocity dependent and position related properties of increased muscle tone measured during a constant velocity stretch. Methods: Elbow flexors were vertically stretched under four different velocities (40, 80, 120, and 160°/s) through a 75° range of motion in 12 patients with hemiparesis, 16 with parkinsonism, and 12 normal controls. From reactive torque measurement, a linear second order model was adopted to dissociate velocity dependent viscous and velocity independent elastic components. The averaged speed dependent reflex torque (ASRT)—defined as the deviation of measured torque from baseline torque—was used to quantify the viscous component of hypertonia. Velocity sensitivity of ASRT (VASRT) and segmented ASRT (SASRT), derived from the slope of the regression line among ASRT velocity plots and from segmentations of reactive torque, respectively, were used to differentiate the increased muscle tone of spasticity and rigidity. Results: ASRT and VASRT were significantly higher in both spasticity and rigidity than in normal controls. SASRT analysis showed three different position related patterns among spasticity, rigidity, and normal groups: spasticity showed progressively increasing muscle tension relative to position; rigidity showed increased (relative to the norm) but constant muscle tone over the entire stretch range; the normal control group showed a consistently low reactive torque over the entire range. Conclusions: Velocity dependence analysis indicates that rigidity and spasticity have approximately equal velocity dependent properties. For differentiating these two types of hypertonia, position dependent properties my be employed.

Objective: Established treatment options for managing severe lower limb spasticity and associated pain are of limited value in people with advanced multiple sclerosis (MS). This has resulted in a resurgence of the use of lumbar intrathecal phenol injection (IP). The aim of this study was to investigate the authors9 experience with IP. Methods: This observational study collected cross sectional data from patients with progressive MS who received IP for severe lower limb spasticity. Data from 25 patients were collected prospectively before and after treatment. In 15 cases the data related to the first treatment and in 10 to serial injections. Outcome measures collected included the Ashworth scale, a spasm frequency scale, a pain rating score, and the percentage achievement of practical goals. Results: After injection, all patients demonstrated reduced lower limb tone bilaterally. After the initial injection there was significant improvement on the targeted as compared with the non-targeted side (Wilcoxon rank p=0.003), while no difference in the degree of improvement between the targeted and non-targeted side was seen after serial injections (Wilcoxon rank p=0.731). Twenty four patients were easier to position and 21 had a reduction in their spasm frequency and intensity. Eleven patients with pain reported benefit. Carers found washing and dressing easier in 16 patients and improved safety when using the hoist in 10. Six patients had recurrence of skin breakdown and five patients reported transient adverse changes in their bowel function. Conclusions: IP can reduce lower limb tone bilaterally after both initial and serial injections. This is most noticeable on the targeted side after initial injection. IP can reduce spasms and pain, leading to improvements in care and overall comfort. IP is an effective treatment option in the management of severe spasticity. Documented selection criteria are essential.