Evidence in practice.

? Clinical question: Is there evidence that botulinum toxin injections are more effective than phenol injections in relieving poststroke reflex activity during plantar flexion, thereby increasing ankle range of motion and improving gait function?

The purpose of "Evidence in Practice" is to illustrate the literature search process to obtain evidence that can guide clinical decision making. This article is not a case report. The examination, evaluation, and intervention sections are purposely abbreviate.

A 60 year-old man was playing tennis when he collapsed on the court with a left cerebrovascular accident (CVA). He was stabilized in acute care, transferred to a rehabilitation facility 2 weeks after his stroke, and then discharged 3 weeks later. At the time of discharge, he could walk 100 feet with "minimal" assistance (ie, he was able to perform 75% of the activity) using a front-wheel walker. We first met the patient 3 months after his stroke to examine him for outpatient rehabilitation.

The patient's primary goal was to return to work as a warehouse supervisor and, eventually, to play tennis. At the time of the examination, he was independent in community mobility but required use of a front-wheel walker (a score of 6 on the Functional Independence Measure [FIM] (1-3)). His score on the Berg Balance Scale (4-5) was 32/56. Elderly patients scoring move than 45/56 are less likely to fall than those scoring less than 45/56. (6) Although we did not consider our patient to be elderly, we thought this score indicated that he could be at risk for falling. He was independent in his remaining basic activities of daily living as measured with the FIM. (1-3)

Cognitively he followed commands well and could communicate his needs. He had selective control of his right hip and knee, meaning that he could move each joint independently of the other but could not move them in synergy. He demonstrated 3-/5 strength at the hip and hamstrings, and 4/5 strength of the quadriceps (based on manual muscle testing (7)). At his ankle, he demonstrated partial selective control in his plantar flexors through gravity-eliminated range of motion. He had substantial increased reflex activity (often, but not consistently, called "spasticity" in the literature) upon quick stretch of his right plantar flexors, which was graded as "3" on the Modified Ashworth Scale. (8) Goniometric examination of passive range of motion (using a procedure described by Norkin and White (9)) of the right lower extremity was normal, with the exception of the right ankle (20[degrees] of plantar flexion; -5[degrees] of dorsiflexion).

During observational gait analysis, (10) the patient demonstrated a forefoot initial contact, followed by reduced knee flexion during weight acceptance. His inability to dorsiflex the ankle prevented adequate progression of the body's center of mass over his base of support during the midstance phase of the gait cycle. Consequently, his contralateral step length was reduced, resulting in an overall decrease in stride length and gait velocity.

We determined that the patient's excessive plantar flexion (ie, loss of dorsiflexion range of motion) was his major deterrent to achieving community ambulation status. Contracture (formation of abnormal crossbridges binding to actin (11)) can be caused by the shortening of the muscle as the result of weakness or mechanical factors during immobilization and also can be the result of neural factors such as paralysis or increased reflex activity. (12) Excessive plantar flexion can lead to a forefoot initial contact as well as decreased progression over the foot during single-limb stance. (10) Excessive plantar flexion has been reported to be the result of increased "stiffness" in the muscle that may not be directly associated with increased reflex activity. (13) In addition, reflex activity does not appear to directly contribute to dysfunction during the stance phase of gait. As the plantar flexors become stretched with forward progression over the stance limb, the active contraction of the gastrocnemius muscle in weight-bearing may dampen the reflex response associated with stretch. (14) Therefore, although increased reflex activity itself may not contribute to gait dysfunction in patients with stroke, (14) it can contribute to restricted range of motion or plantar flexion contracture, (11,15) which can affect gait mechanics. (13,14) Consequently, we decided to reduce reflex activity in the plantar flexors in order to decrease its contribution to contracture.

One month of conservative treatment--including night splinting, prolonged stretching, joint and soft tissue mobilization, and electrical stimulation--did not affect the patient's active or passive dorsiflexion range of motion. Recently, we had attended a professional conference where we heard about the reduction of reflex activity in children with cerebral palsy using botulinum toxin type A as an alternative intervention. This approach has been discussed in the literature by several authors. (16-18) Botulinum toxin injections work at the motor end plate to inhibit the release of acetylcholine, which causes muscle weakness or paralysis. Our patient's referring physician had historically used phenol blocks (injection of a chemical neurolytic that destroys neuronal membranes) to treat increased reflex activity in the gastrocnemius muscle. Before making any recommendations to the referring physician, we decided to search the literature to see if there was any evidence to support the use of botulinum toxin injections (rather than phenol blocks) to control reflex activity in the lower extremity and improve gait function in patients who have had a stroke.

* Database used for search: MEDLINE

MEDLINE is the National Library of Medicine's database for peer-reviewed, health-related literature. The database contains full citations going back to 1966. We chose this database because it is the largest available for health-related literature, We used PubMed as the search engine for MEDLINE. PubMed is free to the public and is accessible through the Internet at www.ncbi.nlm.gov/Pubmed or www.PubMed.gov. The search was performed on May 9, 2003.

* Initial keywords: stroke, spasticity, Botox, phenol, gait

We performed our search using the "PICO" method described by Sackett et al. (19) In the PICO method, our keywords "stroke" and "spasticity" would represent the patient problem [P], "Botox" (the trade name of botulinum toxin A) would represent the intervention [I], "phenol" would represent a comparison intervention [C], and "gait" would represent the desired outcome [O]. Our goal was to develop a search strategy that most accurately represented our clinical question.

The specific terms were determined by using the MeSH (Medical Subject Headings) Database, which is accessed by a link in the left-hand column of the PubMed home page. MeSH terms are the keywords that MEDLINE uses to index articles. The MeSH Database allows users to type a word or phrase into the query box and determine the MeSH terms related to that word. It also has a new feature that allows users to build a search using MeSH terms (for more information on using this search feature see Scalzitti (20)). Because the MeSH search feature searches only the portion of the record containing the MeSH terms used to index the article, we were concerned that using this function might omit relevant articles that did not have the term in that part of its record. We therefore decided to use the MeSH Database to determine the most applicable keywords and then use the main PubMed search screen to conduct our searches.

We clicked on the MeSH Database link and conducted separate searches of the keywords "stroke," "spasticity" (which we believed was the most commonly used term for the phenomenon of increased reflex activity), "Botox," "phenol," and "gait." After determining the proper keywords (MESH terms), we returned to the main PubMed search screen and conducted separate searches for each term. We decided to use the MeSH terms only and not our original keywords, assuming that articles related to our original keyword ("spasticity") would be included under the MeSH term umbrella. Our initial search results are presented in the Table.

After conducting individual searches for each MeSH term, we used PubMed's History function (located on the Features bar underneath the main query box) (Fig. 1) to combine these separate searches using boolean operators (AND, OR, NOT). In PubMed, the complete boolean operator must he capitalized in order to be recognized.

After we clicked on the History link, PubMed displayed a numbered list of our individual searches. We initially combined all 5 MeSH terms by typing #1 AND #2 AND #3 AND #4 AND #5, which corresponded to the search line number for each of our original searches, into the query box; however, no articles were found. Typing #3 AND #2 to combine search line # 3 (Muscle Spasticity) and search line #2 (Botulinum Toxin Type A) yielded 96 articles (search line #7). We then narrowed the results further by typing #7 AND #1 to combine search line #7 (Muscle Spasticity AND Botulinum Toxin Type A) and search line # 1 (Cerebrovascular Accident), which yielded 16 articles (search line #8) (Fig. 2). Finally, we attempted to narrow this search to articles reporting gait outcomes. We typed #8 AND #5 to combine search line #8 with search line #5 (Gait Disorders, Neurologic), which yielded no citations (search line #9).

To find evidence concerning our comparison intervention, phenol, we typed #3 AND #4 to combine search line #3 (Muscle Spasticity) and search line #4 (Phenol), which yielded 83 articles (search line #10). However, when we attempted to narrow the results further by typing #10 AND #1 to combine search line #10 (Muscle Spasticity AND Phenol) and search line #1 (Cerebrovascular Accident), no citations were found (search line #11). Because this search did not turn up any citations, we decided not to conduct further searches on our outcomes keyword (Gait Disorders, Neurologic).

Consequently, we used PubMed's Limits function (located on the left end of the features bar) for search line #10 (Muscle Spasticity AND Phenol). We chose English from the Languages dropdown menu and Human from the Human or Animal dropdown menu. We also decided to use the Publication Types dropdown menu to limit our search according to Sackett's levels of evidence hierarchy. (17) To find systematic reviews, the highest level of evidence, we had 2 options in this menu: Meta-analysis and Review. We first chose Meta-analysis, which did not yield any results. Choosing Review produced one systematic review that focused on reflex activity in the upper extremity. Our patient had increased reflex activity in gastrocnemius muscle and gait problems, and we were looking for articles specific to his problem. Therefore, we continued to search for pertinent articles and chose Randomized Controlled Trial, which is the next highest level of evidence. This selection yielded 3 studies, which are noted by an asterisk in Figure 3. Because this strategy provided few choices, we decided to search by Clinical Trial as well. Although there is increased bias (and dins decreased generalizability) introduced in this research design because of the lack of a control group, we did not feel that we had enough research at the higher levels of evidence (eg meta-analyses, systematic reviews, or randomized controlled trials) to exclude weaker research (eg, nonrandomized clinical trials, cohort studies, case series studies) at this point. This search strategy resulted in 8 citations (Fig. 3), including the 3 randomized control trials we found with the previous search.

* Selection of articles for review: We read each article title to determine if it was relevant to our clinical question. We did not consider articles that studied mechanisms of botulinum toxin type A or phenol, management of reflex activity in the upper extremity, or patient populations with a diagnosis other than stroke, If the title did not make it clear whether the article was pertinent, we then looked at the abstract. Our searches also turned up 7 citations that did not have an abstract. A quick check of these citations revealed that 3 citations were commentaries to all article by Brashear et al (Fig. 2, number 7) and 3 citations were to articles published between 1965 and 1971 that, in our opinion, were probably outdated. Only 3 of the 24 articles listed in Figures 2 and 3 appeared to be relevant to our question (2 from the botulinum toxin search, and 1 from the phenol search). After reading the abstracts, we decided to retrieve the full text of each article from our university's online service for critical appraisal. The abstracts from these articles are reproduced and discussed below. Of these 3 articles, only Kirazli et al (Fig. 3, number 3) compared the effects of botulinum toxin and phenol in patients with stroke. We therefore decided to read this article first.

Kirazli Y, On AY, Kismali B, Aksit R. Comparison of phenol block and botulinus toxin type A in the treatment of spastic foot after stroke: a randomized, double-blind trial. Am J Phys Meal Rehabil. 1998 Nov-Dec; 77(6):510-5.

OBJECTIVE: Locally acting treatments for spasticity such as nerve and motor point blocks have the advantage of reducing harmful spasticity in one area, while preserving useful spasticity in another area. This randomized, double-blinded study is the first trial that was designed to find out whether botulinus toxin Type A and phenol relieves the signs and symptoms of ankle plantar flexion and foot invertor spasticity after stroke and if either of these methods offers any advantages and disadvantages over the other. SUBJECTS: Twenty patients who were included in this preliminary study were randomly assigned to receive a single treatment of 400 mouse units of botulinus toxin type A injected into the calf muscles or to receive a tibial nerve blockade with 3 ml of 5% phenol. OUTCOME MEASURES: A combination of subjective and objective measures were used to assess functional change at baseline and a Weeks 2, 4, 8, and 12. RESULTS: At follow-up, significant improvement (p<0.05) in the Ashworth score for dorsiflexion was observed in both groups. The change in the Ashworth score for eversion was significant in the group that received botulinus toxin Type A (p<0.05) but not in the group that received phenol (p>0.05). When those variables were compared between groups the change in the Ashworth score at weeks 2 and 4 was significantly better in the group that received botulinus toxin Type A (p<0.05) but there was not a significant difference between the groups at Weeks 8 and 12 (p>0.05). The decrease in clonus duration that was detected by electromyography was significant in both groups at all visits, but the decrease in the groups that received botulinus toxin type A was significantly better at Weeks 2 and 4 (p<0.05). CONCLUSION: It is concluded that both motor point injections with botulinus toxin Type A and tibial nerve blockade with phenol are effective in plantar flexion spasticity, but the changes were more significant in the group that received botulinus toxin type A at Weeks 2 and 4, whereas there was not a significant difference between the groups at Weeks 8 and 12. Future research should explore the long-term effect of these two treatment modalities.

[[c] 1998 Association of Academic Physiatrists. Abstract reprinted with permission of Lippincott Williams & Wilkins.]

This randomized controlled trial did not have a control group of subjects who received no intervention; it instead compared botulinum toxin A with phenol. Because phenol is an intervention of longer standing than botulinum toxin, the phenol group would act as a comparison group. This study appeared to directly address the issue of "calf spasticity in patients with stroke" and the intervention and comparison component of our clinical question. The abstract, however, did not address how the observed decreases in calf reflex activity influenced gait function. We nevertheless decided to read the full-text article to get these details.

The 20 subjects studied in this investigation were similar to our patient because they (1) exhibited the presence of severe spasticity (reflex activity) (Ashworth Spasticity Scale score [greater than or equal to] 3), (2) had an onset of increased reflex activity between 3 and 12 months before the start of the study, and (3) were medically stable for at least 2 months. In addition, all patients in the study had not responded to "conventional physical therapy" or medical treatment. Although subject recruitment and randomization methods were not specified, the evaluator and the patients were unaware of which intervention was being provided (ie, botulinum toxin or phenol).

Both groups demonstrated improvement in ankle range of motion over baseline measures; however, the Ashworth scale scores at weeks 2 and 4 were significantly better in the group that received the botulinum toxin injections. No between-group differences were observed at weeks 8 and 12. Before intervention, passive range of motion was limited in 8 patients in the botulinum toxin group and in 7 patterns in the phenol group. In the botulinum toxin group, the mean increase in active range of motion was 20 degrees, and the mean increase in passive range of motion was 22 degrees; the phenol group had mean increases of 17 degrees and 18 degrees, respectively. Although it was unclear whether the patients with range of motion limitations were the same ones who demonstrated improvement in active and passive range of motion, the overall gains in range of motion for both groups appeared to be clinically significant.

With respect to gait function, the botulinum toxin group demonstrated improvements in gait velocity over baseline values at each follow-up visit. The gait velocity of the phenol group, however did not differ from baseline values throughout the course of the study (P>.05).

In the discussion section, the authors addressed the complications they encountered. Three of 10 subjects in the phenol group developed dysesthesia, which was described as being so painful that walking capacity was interrupted for the first 15 days. The authors also had difficulty locating the tibial nerve for the phenol injections in patients who were obese. No adverse events were noted in the botulinum toxin group.

Next, we decided to examine one of the citations retrieved by our botulinum toxin search.

Suputtitada A. Local botulinum toxin type A injections in the treatment of spastic toes. Am J Phys Med Rehabil. 2002 Oct;81 (10):770-5.

OBJECTIVE: To investigate the efficacy and safety of botulinum toxin type A treatment of spastic toes using varying doses based on the degree of spasticity (Modified Ashworth Scale). DESIGN: Single-center, open-label, prospective study. Hemiplegic patients with either hitchhiker's great toes (persistent extension of the great toes) or toe flexor spasms with pain during walking were treated with local intramuscular injections of botulinum toxin type A. Initial botulinum toxin type A dose per muscle was 25 units for patients with a baseline Ashworth score of 2, 50 units for a score of 3, and 75 units for a score of 4. Additional botulinum toxin type A injections were allowed if there was an insufficient clinical response to initial treatment. The muscles injected included flexor digitorum, extensor hallucis longus, and/or flexor hallucis longus. All injections were made using electromyographic guidance. Outcome measures were the Modified Ashworth Scale, a visual pain scale, a visual percentage of function scale, and adverse effects. RESULTS: Twenty patients were enrolled. The dose of botulinum toxin type A used ranged from 25 to 35 units per muscle for an Ashworth score of 2, from 50 to 70 units per muscle for a score of 3, and from 75 to 95 units per muscle for a score of 4. There were improvements in all outcome measures. In most patients, the benefits lasted 5-6 mo, with a few patients exhibiting benefits for > or =2 yr. There were no adverse effects. CONCLUSIONS: Botulinum toxin type A treatment using doses based on spasticity severity seems to be safe and effective in the

treatment of spastic toes, and further study is warranted.

[[c] 2002 Association of Academic Physiatrists. Abstract reprinted with permission of Lippincott Williams & Wilkins.]

This nonrandomized clinical study focused on increased reflex activity in toe flexors and extensors rather than in the gastrocnemius muscle; however, this investigation raised important issues that were relevant to our clinical question. First, the authors suggested that botulinum toxin could have a long-lasting effect. Similar to the study by Kirazli et al, the maximum effects of the botulinum toxin injection on reducing reflex activity occurred within 2 to 8 weeks. From 8 weeks to 24 weeks, reflex activity slowly returned to the preinjection level. Second, although this study did not use any functional outcome measures, it did measure patient perceptions of normal function using a 0%-100% scale. Patient perception of normal function was approximately 15% at baseline, increased steadily during the first 8 weeks until it reached 100%, and remained above 60% throughout the remaining 16 weeks of the study. The perceived increase in function suggests that patients might be able to practice functional tasks using their improved dorsiflexion range of motion with an improved biomechanical strategy during the period when increased reflex activity was lowest. Although increased reflex activity returned to preinjection levels, patients believed that they were still able to maintain some of their functional gains.

We chose to read a review article, hoping that it would lead us to additional studies evaluating the effect of botulinum toxin on patients with reflex activity during plantar flexion resulting from stroke.

O'Brien CF. Treatment of spasticity with botulinum toxin. Clin J Pain. 2002 Nov-Dec;18(6 Suppl):S182-90.

Spasticity is an abnormal increase in muscle contraction often caused by damage to central motor pathways that control voluntary movement. During clinical examination, spasticity manifests as an increase in stretch reflexes, producing tendon jerks and resistance appearing as muscle tone. There are many causes of spasticity, including demyelination from multiple sclerosis, congenital damage from diseases such as cerebral palsy, trauma to the brain or spinal cord, hemorrhage or infarction, and other pathologic conditions that interrupt neural pathways. Effects of spasticity range from mild muscle stiffness to severe, painful muscle contractures and repetitive spasms that reduce mobility and substantially impede normal activities of daily living. Botulinum toxin therapy reduces spasticity and pain associated with several disorders. Local treatment with botulinum toxins can be used as adjunctive therapy, along with oral anti-spasticity medications, or alone to provide localized decrease in symptoms of spasticity and pain. Botulinum toxin therapy may be particularly useful for patients with spasticity due to stroke, whose treatment can be tailored based on recovery of function over time. In addition, botulinum toxin therapy is safe for pediatric patients, including children with cerebral palsy, who may not be able to tolerate the cognitive side effects of oral medications. Results of studies evaluating botulinum toxin for the treatment of spasticity due to various causes are presented here.

[[c] 2002 Lippincott Williams & Wilkins. Abstract reprinted with permission of Lippincott Williams & Wilkins.]

This nonsystematic review indicated that botulinum toxin therapy may be useful for patients with increased reflex activity due to stroke. Although the authors summarized 6 studies that evaluated the effects of botulinum toxin on reflex activity, all of the studies involved muscles of the upper limb. In general, all studies reported beneficial outcomes for reducing reflex activity, but were inconsistent with regard to functional gain.

The authors did mention one review article on the use botulinum toxin for increased reflex activity in the lower extremity (Hesse et al, 2001). Because this review did not surface in our initial search, we entered the author name into the PubMed search screen (using the Publication Year limit) to find the abstract, which is reproduced below. Unfortunately, this journal was not available in our campus library. The abstract indicated positive outcomes for reducing lower-limb reflex activity and improving walking function; however, we were unable to critically appraise the article.

Hesse S, Brandi-Hesse B, Bardeleben A, Werner C, Funk M. Botulinum toxin A treatment of adult upper and lower limb spasticity. Drugs Aging. 2001;18(4):255-62.

This article discusses the treatment of spasticity with botulinum toxin A as a new approach in the neurological rehabilitation of patients after stroke. Clinical studies have been reviewed to provide information about target groups, technical aspects and the advantages and disadvantages of treating spasticity with botulinum toxin A. Open and controlled studies showed that the intramuscular injection of Dysport 500 to 1,500U or Botox 100 to 300U could reversibly relieve upper limb flexor and lower limb extensor spasticity. A reduced muscle tone, pain relief, better hand hygiene and improved walking function were the main benefits. Patients tolerated the treatment well. Activity or, if not possible, electrical stimulation of the injected muscles may enhance the effectiveness of the costly toxin. Serial casting is another option. With respect to the action of botulinum toxin A, it is suggested that the effect of the toxin could be mediated by paresis of both the extrafusal and intrafusal muscle fibres, thereby altering the afferent discharge in the muscle.

[[c] 2001 Adis International. Abstract reprinted with permission of Adis International.]

* Clinical decision: According to Sackett et al, (19) decisions about patient care should be based on 3 elements: scientific evidence, clinical expertise, and patient preferences. In addition to our own clinical judgment, expert professional opinion also can be consulted.

Although our search yielded numerous articles related to these 2 interventions, only 3 (Kirazli et al, Suputtitada, and O'Brien) fit our patient's problem and desired outcome. Of these studies, only 1 (Kirazli et al) directly compared the effects of botulinum toxin and phenol for reducing reflex activity during plantar flexion and improving gait function in patients after CVA.

Of the studies reviewed, the one most relevant to our clinical question (Kirazli et al) was a randomized controlled trial. although the sample size of this study was low (20 subjects), this trial provided direct evidence that botulinum toxin may be more effective than phenol in the short term for reducing reflex activity in the calf muscles and improving gait function. The other 2 articles we considered in making our clinical decision provided additional evidence (although the Suputtitada article provided weaker evidence due to its non-randomized study design) that botulinum toxin may be a viable alternative to phenol; however, direct comparisons between the 2 treatments were not made.

In terms of expert clinical judgment, we had few sources to rely on. We had no experience with this intervention, and thus could not rely on our own clinical expertise. Anecdotal "testimonials" from speakers at a professional conference seemed to advocate botulinum toxin as an alternative to phenol for reduction of reflex activity. Whether these speakers had any association with a pharmaceutical company is unknown. In addition, most discussion at the conference concerned children with cerebral palsy, not patients such as ours. The use of botulinum toxin in patients with stroke was discussed as pure speculation. Consequently, we had little expert clinical judgment or opinion to rely on.

Ore patient preferred any intervention that would help him to achieve his goals as quickly as possible. Based on our literature review, botulinum toxin seems to reach its full effect quicker than phenol and may have fewer side effects. Although botulinum toxin injections can be expensive, this form of therapy was approved by our patient's insurance carrier.

In our clinical decision-making process, we considered scientific evidence, expert opinion, and patient preferences. Expert opinion made no significant contribution to our decision making. Our patient preferred the quickest results, which appeared to favor the use of botulinum toxin over phenol. Scientific evidence was weak, with only one randomized controlled trial (which was not of high quality), one nonrandomized clinical study, and one review article available. Although we could not definitively state that botulinum toxin was better than phenol at reducing reflex activity and improving gait function in patients with stroke, it did appear to be a viable alternative. We therefore recommended the use of botulinum toxin when we referred the patient back to his physician. We discussed our rationale with the physician over the phone and followed up our phone call with a written monthly progress note and a copy of the article by Kirazli et al, which he had requested. Based on our recommendation, the evidence provided, and the expert consensus he solicited from other colleagues, the physician subsequently decided to use botulinum toxin.

Figure 2. Citations retrieved by the search using the keywords "Muscle Spasticity" AND "Botulinum Toxin Type A" AND "Cerebrovascular Accident" (search line #8 in Fig. 1).

1. O'Brien CF. Treatment of spasticity with botulinum toxin. Clin J Pain. 2002 Nov-Dec;18(6 Suppl):S182-90

2. Dobkin BH. Botulinum toxin for spasticity after stroke. N Engl J Med. 2003 Jan 16;348(3):258-9; author reply 258-9. No abstract available.

3. Buitrago MM, Koolwijk I. Botulinum toxin for spasticity after stroke. N Engl J Med. 2003 Jan 16;348(3):258-9; author reply 258-9. No abstract available.

4. Landau WM. Botulinum toxin for spasticity after stroke. N Engl J Med. 2003 Jan 16;348(3):258-9; author reply 258-9. No abstract available.

5. Pandyan AD, Vuadens P, van Wijck FM. Stark S, Johnson GR, Barnes MP. Are we underestimating the clinical efficacy of botulinum toxin (type A)? Quantifying changes in spasticity, strength and upper limb function after injections of Botox to the elbow flexors in a unilateral stroke population. Clin Rehabil. 2002 Sep;16(6):654-60.

6. Suputtitada A. Local botulinum toxin type A injections in the treatment of spastic toes. Am J Phys Med Rehabil. 2002 Oct;81 (10):770-5.

7. Brashear A, Gordon MF, Elovic E, Kassicieh VD, Marciniak C, Do M, Lee CH, Jenkins S, Turkel C; Botox Post-Stroke Spasticity Study Group. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. N Engl J Med. 2002 Aug 8;347(6):395-400.

8. Rowland LP. Stroke, spasticity, and botulinum toxin. N Engl J Meal. 2002 Aug 8;347(6):382-3. No abstract available.

9. van Kuijk AA, Geurts AC, Bevaart BJ, van Limbeek J Treatment of upper extremity spasticity in stroke patients by focal neuronal or neuromuscular blockade: a systematic review of the literature. J Rehabil Med 2002 Mar;34(2):51-61. Review.

10. Francisco GE, Boake C, Vaughn A. Botulinum toxin in upper limb spasticity after acquired brain injury: a randomized trial comparing dilution techniques. Am J Phys Med Rehabil. 2002 May;81 (5):355-63.

11. Bakheit AM, Pittock S, Moore AP, Wurker M, Otto S, Erbguth F, Coxon L. A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke. Eur J Neural. 2001 Nov;8(6):559-65.

12. Radensky PW, Archer JW, Dournaux SF, O'Brien CF. The estimated cost of managing focal spasticity: a physician practice patterns survey. Neurorehabil Neural Repair. 2001 ;15(1):57-68.

13: Bakheit AM, Thilmann AF, Ward AB, Poewe W, Wissel J, Muller J, Benecke R, Collin C, Muller F, Ward CD, Neumann C. A randomized, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo in upper limb spasticity after stroke. Stroke. 2000 Oct;31 (10):2402-6.

14. Bhakta BB, Cozens JA, Chamberlain MA, Bamford JM. Impact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomised double blind placebo controlled trial. J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):217-21

15. Davis EC, Barnes MP. Botulinum toxin and spasticity. J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):143-7. No abstract available.

16. Lagalla G, Danni M, Reiter F, Ceravolo MG, Provinciali L. Post-stroke spasticity management with repeated botulinum toxin injections in the upper limb. Am J Phys Med Rehabil. 2000 Jul-Aug;79(4):377-84.

Figure 3. Citations retrieved by search using the keywords "Muscle Spasticity" AND "Phenol" with limit options of "Clinical Trial," "English," and "Human" (search line #15 in Fig. 1).

1. Albert TA, Yelnik A, Bonan I, Lebreton F, Bussel B. Effectiveness of femoral nerve selective block in patients with spasticity: preliminary results. Arch Phys Med Rehabil. 2002 May;83(5):692-6.

* 2. On AY, Kirazli Y, Kismali B, Aksit R. Mechanisms of action of phenol block and botulinus toxin Type A in relieving spasticity: electrophysiologic investigation and follow-up. Am J Phys Med Rehabil. 1999 Jul-Aug;78(4):344-9.

* 3. Kirazli Y, On AY, Kismali B, Aksit R. Comparison of phenol block and botulinus toxin type A in the treatment of spastic foot after stroke: a randomized, double-blind trial. Am J Phys Med Rehabil. 1998 Nov-Dec;77(6):510-5.

4. Yadav SL, Singh U, Dureja GP, Singh KK, Chaturvedi S. Phenol block in the management of spastic cerebral palsy. Indian J Pediatr. 1994 May-Jun;61(3):249-55.

* 5. Wassef MR. Interadductor approach to obturator nerve blockade for spastic conditions of adductor thigh muscles. Reg Anesth. 1993 Jan-Feb; 8(1): 13-7.

6. Bjerre I, Blennow G. Methocarbamol in the treatment of cerebral palsy in children. Neuropadiatrie. 1971 Oct;3(2):140-6. No abstract available.

7. Levine IM, Jossmann PB, Rudd J, De Angelis V. The quantitative evaluation of intravenous methocarbamol in the relief of spasticity. Neurology. 1968 Jan;18(1 Pt 1):69-74. No abstract available.

8. Cooper IS, Hirose T, Matsuoka S, Roth D, Waltz JM, Ericsson AD. Specific neurotoxic perfusion: a new approach to selected cases of pain and spasticity. Neurology. 1965 Nov;15(11):985-93. No abstract available.

Table. Initial Search Results Using Medical Subject Heading
(MeSH) Terms

                                            Number of   Search
                                            MEDLINE     Line
Initial Term   MeSH Term                    Citations   Number

Stroke         Cerebrovascular Accident      25,204     1
Botox          Botulinum Toxin Type A         1,120     2
Spasticity     Muscle Spasticity              4,267     3
Phenol         Phenol                       101,517     4
Gait           Gait Disorders, Neurologic       405     5

? In the next Evidence in Practice: Ellen Wetherbee, PT, MEd, OCS, and Geraldine L Pellecchia, PT, PhD, will seek evidence to answer the question, "Is there evidence that bracing could provide adequate stability for a 47-year-old man with a deficient anterior cruciate ligament to resume downhill skiing?" (Coming in March 2004)

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Jody Cormack, PT, DPT, NCS, is Associate Professor, Department of Physical Theraphy, California State University Long Beach, Long Beach. Calif.

Christopher M Powers, PT, PhD, is Associate Professor, Department of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, Calif.