Botulinum toxin and mirror therapy: A new approach for poststroke spasticity

Botulinum toxin and mirror therapy: A new approach for poststroke spasticity

Abstracts / Toxicon 123 (2016) S2eS90 193. EFFECTIVENESS OF BOTULINUM TOXIN TYPE A FOR TREATING UPPER LIMB SPASTICITY Yuliya Rushkevich*, Sergei Likh...

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Abstracts / Toxicon 123 (2016) S2eS90

193. EFFECTIVENESS OF BOTULINUM TOXIN TYPE A FOR TREATING UPPER LIMB SPASTICITY Yuliya Rushkevich*, Sergei Likhachev. Republican Research and Clinical Center of Neurology and Neurosurgery, Department of Neurology, Minsk, Belarus * Corresponding author: Department of Neurosciences, University Hospital of Udine, p.le Santa Maria della Misericordia 15, Udine, 33100, Italy. E-mail address: [email protected]

Introduction and objectives: The high prevalence of stroke is a global problem causing well-known long-term disabilities, one of which is spasticity. Upper limb spasticity (ULS) can generally reduce the ability to undertake activities of daily living, personal hygiene, and ambulation. ULS can have a disabling effect because of pain and reduced mobility in the stroke survivor, which may limit the potential effects of rehabilitation. We aimed to evaluate the efficacy and safety of botulinum toxin type A (BTA) injections in patients with poststroke ULS. Methods: We investigated 65 patients with poststroke spasticity of the upper limb. Patients were randomly assigned to a main group of 23 patients (male/female 15/8); median age, 50 years (39, 54); median time of stroke onset, 13.6 months prior (11, 34) who were treated with BTA; or to a

Characteristic Value

Number Of CYs

%CYs w/ TT

RR Ratios

All CwCP Age

7,158 749 2,070 1,921 1,788 630 1,669 1,010 1,554 1,620 1,044 261 1,194 2,216 1,669

9.4% 10.4% 13.2% 9.1% 6.9% 3.7% 11.9% 9.3% 13.8% 5.4% 7% 2.3% 5.1% 17.5% 13.8%

1.12 1.68* 0.96 0.68* 0.37* 1.38* 0.99 1.69* 0.51* 0.71* 0.24* 0.50* 3.01* 1.70*

2,630 208

12% 25%

1.52* 2.79*

US Region

Comorbidity MES

patients in the main group: moderate (MAS score ¼ 2) in 18 (78.26%) and mild in 5 patients (MAS score 1+). In the control group, spasticity remained severe in 34 (76.19%) and moderate in 8 patients. On assessment of pain, a reliable decrease was observed only in patients in the main group (P¼0.0006). We observed improved quality-of-life scores (as per the SF36) on average for 20% to 30% of patients in the main group. Conclusions: The results of this study of BTA treatment in upper limb spasticity suggest that BTA injections safely and effectively decreased muscle tone and pain and lessened functional disability. BTA therapy will allow improved quality of life in poststroke patients. Keywords: Botulinum toxin; Modified Ashworth Scale; Poststroke spasticity; Visual Analog Scale 194. ASSESSMENT OF BOTULINUM TOXIN TREATMENT IN PEDIATRIC CEREBRAL PALSY PATIENTS IN THE UNITED STATES' MANAGED MEDICAID POPULATION Tia Goss Sawhney a, *, Savreet Bains b, Sonia Pulgar b, Bruce Pyenson a, Christine Ferro a, Judy Gooch c, Garey Noritz d, Edward Wright e. a Milliman, New York, NY, USA; b Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; c Utah Neuro Rehabilitation, Murray, UT, USA; d Nationwide Children’s Hospital, Columbus, OH, USA; e Dell Children’s Medical Center, Austin, TX, USA * Corresponding author: Milliman, 1 Pennsylvania Plaza, 38th Floor, New York, NY 10119, USA. E-mail address:[email protected]

Table 1 Characteristics of TT in CwCP.

2-3 4-8 9-13 14-18 19-20 North West North Central North East South West South Central South East Intellectual impairment Quadriplegic CP Enteral & parenteral nutrition Incontinence Mechanical ventilation

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* P value <5%.

control group of 42 patients (male/female 26/16); median age, 55 years (51, 60); median time of stroke onset, 13 months prior (9, 35) who were treated with oral antispasticity medications. All participants received occupational therapy for 2 weeks, using neurodevelopmental and biomechanical approaches and an activity-based home program. Exclusion criteria were fixed contracture or muscle atrophy in the spastic limb. The tone of upper limb muscles was assessed at baseline and at 4 weeks using the Modified Ashworth Scale (MAS). Pain was estimated by Visual Analog Scale (VAS), and we determined the quality of life of poststroke patients with the Short Form 36 (SF-36) Health Survey. BTA was injected in a dose of 1000 U in the target muscles of the upper limb, defined under ultrasonographic monitoring. Results: A majority of patients had severe spasticity at baseline (MAS score  3): in the main group, 14 (93.3%) and in the control group, 34 (80.9%), had moderate pain: median VAS was 4 (3, 5) in the main group and 4 (3, 4) in the control group. Patients in the main group received intramuscular BTA injections without complications. The onset of clinical effect after an injection of BTA was 1 to 3 days on average after introduction, with increase of action to 3 weeks. Two patients had mild weakness of the fingers as side effect, which continued for 1 week. After 4 weeks, we determined decreasing spasticity by MAS in all

Set Set Set Set

1 2 3 4

Patients Patients Patients Patients

were were were were

treated treated treated treated

with: with: with: with:

BoNT-A BoNT-A BoNT-A

TPT TPT

MT

TPT

MT

Introduction: Botulinum toxin treatment (TT) has been used for >20 years to treat spasticity in children with cerebral palsy (CwCP). The American Academy of Neurology recommends offering TT in CwCP for facilitating mobility, palliative relief, and ease of care management. In the US, little is known about the demographics, comorbidities, and functional status of CwCP receiving TT. Methods: CwCP aged 2-20 years with 11 months of coverage in a calendar year (CY) were identified in a US managed Medicaid insurance claims database covering 15+ states. For each CY, CwCP’s TT use, demographics, comorbidities, and use of medical equipment and supplies (MES) were assessed. Comorbidities were designated using HHS-Hierarchical Condition Categories (HCCs). Relative risk (RR) ratios were calculated, with TT as the dependent variable. Results: 7,158 CYs of data were identified for 3,294 unique CwCP. 9.4% (674) of the CYs had TT. TT usage decreased by age. TT varied significantly by region. CwCP with intellectual impairment (HCCs 096-103) were less likely to receive TT. CwCP with quadriplegia (HCC 112) and MES suggestive of nonambulatory status were more likely to receive TT. Conclusions: In this analysis, TT was used more in younger CwCP, and had significant regional variation. CwCP with quadriplegia or MES indicative of nonambulatory status had higher TT use than overall CwCP. Keywords: Botulinum; Cerebral palsy; Children; Spasticity; Toxin 195. BOTULINUM TOXIN AND MIRROR THERAPY: A NEW APPROACH FOR POSTSTROKE SPASTICITY Anna Scalise a, *, Marco Toffoli a, Luca Grassetti b, Carolina Gentile a, Katia Troiero a, Sara Simeoni a, Laura Rizzi b, Luigi Gigli Gian a. a Department of Neurosciences, University Hospital of Udine, Udine, Italy; b Department of Economics and Statistics, University Hospital of Udine, Udine, Italy * Corresponding author: Department of Neurosciences, University Hospital of Udine, p.le Santa Maria della Misericordia 15, Udine, 33100, Italy. E-mail address:

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Abstracts / Toxicon 123 (2016) S2eS90

[email protected]

Introduction and objectives: Stroke is one of the major causes of death and disability worldwide; this burden is increasing due to an aging population and unhealthy lifestyle habits (Bejot 2007). Paresis and spasticity of the upper limb are the most frequent and impacting consequences of stroke. Poststroke spasticity can develop as early as 1 week after stroke, and it is estimated to occur in up to half of stroke survivors, with social, medical, and economic burdens (Allison 2015; Urban 2010). The aim of treatment in patients with poststroke spasticity is focused on reduction of muscle limb overactivity. Several types of treatments can be used to alleviate poststroke spasticity, including physical therapy, systemic and intrathecal medications, and surgery. The gold-standard therapy for focal spasticity after stroke is botulinum toxin type A (BoNT-A) (Kinnear 2014; Simpson 2008). After BoNT-A treatment, it is current practice to offer patients additional rehabilitation therapy, but the evidence supporting this multidisciplinary approach is not strong (Franceschini 2014). There is growing evidence supporting mirror therapy (MT), a simple and inexpensive new technique of rehabilitation, as a useful tool in addition to traditional physiotherapy (TPT) in treating arm paresis in stroke patients (Pollock 2014; Ramachandran 1995; Deconinck 2015), BoNT-A, MT, and TPT treatments, applied individually or otherwise combined in patients with upper-limb spasticity poststroke, were compared. Our objective was to evaluate the gold standard among the functional treatments of spasticity. Methods: We consecutively recruited 61 patients with poststroke upper limb spasticity. Patients with severe cognitive impairment or other serious Table 1 Sample Description.

Observations Males Females Age < 70 years Age > 70 years Stroke within 60 months from enrollment Stroke older than 60 months from enrollment Hemorrhagic stroke Ischemic stroke Dominant hemisphere affected Nondominant hemisphere affected

Set 1

Set 2

Set 3

Set 4

Total

37 25 12 20 17 17

37 21 16 18 19 20

18 13 (72%) 5 (72%) 5 (28%) 13 (72%) 7 (39%)

12 10 (83%) 2 (17%) 7 (58%) 5 (42%) 5 (42%)

104 69 (66%) 35 (34%) 50 (48%) 54 (52%) 49 (47%)

(68%) (32%) (54%) (46%) (46%)

(57%) (43%) (49%) (51%) (54%)

20 (54%) 17 (46%) 11 (61%) 7 (58%)

55 (53%)

12 (32%) 10 (27%) 3 (17%) 1 (8%) 26 (25%) 25 (68%) 27 (73%) 15 (83%) 11 (92%) 78 (75%) 15 (44%) 9 (27%) 5 (33%) 4 (44%) 33 (36%) 19 (56%) 24 (73%) 10 (67%) 5 (56%)

58 (64%)

comorbidities that might interfere with the treatments were excluded. Subjects were assigned to 1 of 4 treatment sets, according to their possibilities (logistical management of the rehabilitation program) to undergo a given treatment: Given the transient effect and the reversibility of BoNT-A (Hallett 2015), patients were treated several times with a different treatment set, at intervals of at least 4 months. For statistical purposes, each treatment was counted independently for a total of 104 “observations”. Immediately before and at the end of each treatment set the following variables were evaluated in the affected arm: Modified Ashworth Scale (MAS), the Motricity Index (MI), the EuroQOL-5D (EQ-5D), and the Barthel Index. The beneficial effects of different combinations of MT, TPT, and BONT-A were analyzed by comparing the improvements in and between treatment sets. Results: Demographic data are reported in Table 1. Proportions of improved, unchanged, and worsened observations for each set are shown in Table 2. The results in Table 3 show the empirical significance levels for the Wilcoxon rank sum test for improvements in motor function. Patients in set 1 reached significant improvement (P<0.05) in all scales used. On the contrary, results for patients in set 4 were inconsistent in all scales. Patients in set 2 and set 3 reached intermediate outcomes. Conclusions: To our best knowledge, the beneficial effects of the combination of MT, TPT, and BONT-A in poststroke spasticity have never been assessed before. Moreover, given the different mechanisms of action, we hypothesized that MT, BoNT-A, and TPT may have a synergistic effect in the treatment of motor function in stroke patients that goes beyond that of each treatment taken individually. In particular, MT and BoNT-A may have a synergistic effect in modulating maladaptive cortical plasticity, which may contribute to poststroke plasticity. We conclude that a multimodal neurorehabilitation strategy is more effective than a single therapy to promote recovery of function and reduce spasticity of the upper extremity in chronic stroke patients. Keywords: Botulinum toxin; Mirror therapy; Neurorehabilitation; Plasticity; Spasticity, Stroke References Allison R, Shenton L, Bamforth K, Kilbride C, Richards D. Incidence, time course and predictors of impairments relating to caring for the profoundly affected arm after stroke: a systematic review. Physiother Res Int. 2015. http://dx.doi.org/10.1002/pri.1634. [Epub ahead of print] Bejot Y, Benatru I, Rouaud O, et al. Epidemiology of stroke in Europe: geographic and environmental differences. J Neurol Sci. 2007;262(1-2):8588. Deconinck FJ, Smorenburg RP, Benham A, Ledebt A, Feltham MG, Savelsbergh GJP. Reflections on mirror therapy: a systematic review of the effect of mirror visual feedback on the brain. Neurorehabil Neural Repair. 2015;29(4):349-361.

Table 2 Results of Treatment Sets on Conventional Outcome Measures. MI

Set Set Set Set

1 2 3 4

MAS

BI

EQ-5D

Better

Unchanged

Worse

Better

Unchanged

Worse

Better

Unchanged

Worse

Better

Unchanged

Worse

48.6% 16.2% 22.2% 25.0%

43.2% 72.9% 72.2% 41.6%

8,1% 10,8% 5,5% 33,3%

86.4% 75.6% 77.7% 50.0%

2.7% 8.1% 5.5% 25.0%

10.8% 16.2% 16.6% 25.0%

43.2% 35.1% 11.1% 25.0%

45.9% 51.3% 50.0% 50.0%

10.8% 13.5% 38.8% 25.0%

56.76% 41.67% 38.89% 33.33%

27.0% 36.1% 38.8% 33.3%

16.2% 22.2% 22.2% 33.3%

BI¼Barthel Index; EQ-5D¼EuroQOL-5D; MAS¼Modified Ashworth Scale; MI¼Motricity.

Table 3 Significance Levels in Wilcoxon Rank Sum Test for Improvements in Motor Function.

Set Set Set Set

1 2 3 4

MI

MAS

BI

EQ-5D

0.00069 0.05695 0.13591 0.53338

0.00001 0.00221 0.00799 0.1421

0.00088 0.01272 0.7818 0.6251

0.0022 0.11773 0.09855 0.26431

EQ-5D¼EuroQOL-5D;

MAS¼Modified

BI¼Barthel Index; MI¼Motricity Index.

Ashworth

Scale;

Franceschini M, Iocco M, Molteni F, Santamato A, Smania N. Management of stroke patients submitted to botulinum toxin type A therapy: a Delphi survey of an Italian expert panel of specialist injectors. Eur J Phys Rehabil Med. 2014;50(5):525-533. Hallett M. Explanation of timing of botulinum neurotoxin effects, onset and duration, and clinical ways of influencing them. Toxicon. 2015;107(Pt A):64-67. Kinnear BZ, Lannin NA, Cusick A, Harvey LA, Rawicki B. Rehabilitation therapies after botulinum toxin-A injection to manage limb spasticity: a systematic review. Phys Ther. 2014;94(11):1569-1581. Pollock A, Farmer SE, Brady MC, et al. Interventions for improving upper