PROGRESSSIVE HIP SUBLUXATION leading to hip dislocation

Transcription

1 431 Hip Migration Percentage in Children With Cerebral Palsy Treated With Botulinum Toxin Type A Frank S. Pidcock, MD, David E. Fish, MD, MPH, Doug Johnson-Greene, PhD, ABPP, Isabel Borras, MD, John McGready, MS, Charles E. Silberstein, MD ABSTRACT. Pidcock FS, Fish DE, Johnson-Greene D, Borras I, McGready J, Silberstein CE. Hip migration percentage in children with cerebral palsy treated with botulinum toxin type A. Arch Phys Med Rehabil 2005;86: Objective: To determine hip radiographic findings in children with cerebral palsy (CP) treated with botulinum toxin type A (BTX-A). Design: Retrospective chart review with correlation to radiographic findings. Setting: Academic center. Participants: Sixteen subjects with CP. Intervention: BTX-A treatment to adductor muscles. Main Outcome Measure: The Reimers hip migration percentage before and after BTX-A. Results: Thirty-two hips in 16 children with CP were treated. We examined the effect of initial migration percentage and initial migration percentage age on the change in migration percentage after BTX-A injection. A significant effect for initial migration percentage ( 30% or 30%; F 19.05, P.001) and a significant interaction between initial migration percentage and initial migration percentage age (F 7.5, P.01) was noted. migration percentage age ( 24mo or 24mo) was not significant (F.95, P.34). Patients who had an initial migration percentage of 30% or more and were less than 24 months old were more likely to have a decrease in migration percentage after BTX-A injection compared with patients who were older than 24 months and who had an initial migration percentage of 30% or more. Conclusions: Improvement in hip migration percentage after BTX-A injection is a function of age and the initial migration percentage. BTX-A injections to adductor muscles may be beneficial for some children with CP. Key Words: Botulinum toxin type A; Cerebral palsy; Hip; Rehabilitation by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation From the Departments of Physical Medicine and Rehabilitation (Pidcock, Johnson- Greene) and Orthopaedic Surgery (Silberstein), Johns Hopkins University School of Medicine (McGready), Baltimore, MD; Department of Orthopaedics and Physical Medicine and Rehabilitation, UCLA School of Medicine, Los Angeles, CA (Fish); and Sinai Hospital, Baltimore, MD (Borras). Presented in part to the American Academy of Physical Medicine and Rehabilitation, November 5, 2000, San Francisco, CA. Supported by Allergan honoraria (unrestricted educational grant). An organization, with which 1 or more of the authors is associated, has received or will receive financial benefits from a commercial party having a direct financial interest in the results of the research supporting this article. Pidcock has received unrestricted educational grants from Allergen, has been a coinvestigator on a multicenter clinical trial sponsored by Allergen, and has attended educational meetings sponsored by Allergen. Fish has been a consultant to Allergen and has spoken for Allergen. Reprint requests to Frank S. Pidcock, MD, Kennedy Krieger Institute, 707 N Broadway, Baltimore, MD 21205, pidcock@kennedykrieger.org /05/ $30.00/0 doi: /j.apmr PROGRESSSIVE HIP SUBLUXATION leading to hip dislocation is a common and serious problem in children with cerebral palsy 1,2 (CP). Consequences may include seating difficulties, pain, gait deterioration, and problems with perineal hygiene. 3 The incidence of dislocation varies according to the severity of spasticity, with an average frequency in most series of 25% to 30%. 4 A study 5 of a geographically defined population of children with CP showed that, as early as 18 months of age, their percentage of femoral head migration measured on hip radiography was significantly greater than that found in a normally developing population. These investigators recommended screening all children with bilateral CP to look for hip subluxation, using the migration percentage of the femoral head. The migration percentage is measured by calculating the percentage of the femoral head that lies outside of the lateral border of the acetabulum as defined by bony landmarks on an anteroposterior pelvis radiograph 6 (fig 1). If the femoral head remains within the acetabulum until around age 4 to 5 years, then the chance of developing a stable, pain-free hip is much greater. 7,8 Following the migration percentage is a useful predictor for determining the risk of subluxation and the effectiveness of interventions. Miller and Bagg 1 found that the hips of children with CP who were younger than 8 years and had a migration percentage of less than 30% were less likely to progress to dislocation than were the hips of children with a migration percentage of more than 30%. If the migration percentage was greater than 60%, complete dislocation of the hips without surgical intervention was reported. Injection of botulinum toxin type A (BTX-A) has been used as an adjunctive measure to supplement interventions to prevent or delay the lateral migration of the femoral head in children with CP. 4,9 These interventions include muscle stretching and static devices such as standing frames and abduction braces. 4,10 BTX-A consists of purified protein products of Clostridium botulinum that induces a transient chemodenervation at the neuromuscular junction, reducing muscle activity in spastic muscles. 11,12 The purpose of this study was to determine whether radiographic evidence of hip subluxation, measured by the migration percentage, changes after BTX-A injections into spastic adductor muscles of children with CP. Adductor muscles were chosen for treatment because the biomechanic pull of this muscle group is believed to be the most important contributor to hip subluxation and progressive hip deformity. 13,14 METHODS Sixteen patients with spastic CP who had hip radiographs within 6 months before BTX-A injections to bilateral hip adductor muscles and a follow-up hip radiograph within 7 months after treatment were identified from a clinical database that included information on patients who had received therapeutic botulinum toxin injections from 1996 to Patients were excluded if hip surgery was performed before a hip radiograph after BTX-A treatment. Concurrent use and adjust-

2 432 HIP MIGRATION PERCENTAGE AND BTX-A, Pidcock lying lateral to the Perkins line was divided by the width of the femoral head to determine the migration percentage. This fraction is expressed as a percentage of the whole width of the femoral head. A change of more than 10% in hip migration percentage was considered clinically significant. 1 The migration percentage measurements were done by the same person. The dose of therapeutic BTX-A (Botox) per muscle was selected based on muscle size and the desired treatment effect. The average total dose of BTX-A given to an adductor muscle was 63U (range, U). The average dose per kilogram of body weight was 5.3U/kg of muscle (range, U/kg of muscle). The BTX-A was diluted to a concentration of 100U/mL and injected intramuscularly using a 27-gauge needle guided by palpation or electromyographic localization. All injections were either performed or supervised by the same provider. RESULTS Fig 1. The Reimers migration percentage is the percentage of the femoral head lying lateral to Perkins line (P), which is drawn perpendicular to Hilgenreiner s line (H). Note that MP A/B 100. ment of antispasticity medications was allowed during the study period. A migration percentage was calculated from each study radiograph using the Reimers criteria 6 to determine the lateral displacement of the femoral head from its normal position in the acetabulum. Anteroposterior view radiographs of the hips in neutral position with the legs parallel were used. A horizontal line was drawn at the level of the Y-cartilages (Hilgenreiner s line) connecting the innermost parts of the iliac bones. A perpendicular line was drawn to this line through the acetabular edge (Perkins line). The amount of the femoral head Patient Characteristics Sixteen patients (32 total hips), who included 11 boys and 5 girls, were evaluated (table 1). Twelve had a diagnosis of tetraplegic CP and 4 were diagnosed with diplegic CP. The average age at the time of the initial migration percentage measurement was months (range, 9 43mo). The BTX-A injections were given at an average age of months (range, 13 45mo) and the postinjection migration percentages were measured at an average age of months (range, 14 49mo). At the time of the BTX-A injection, 2 patients were younger than 12 months, 7 were between 13 and 24 months, 3 were between 25 and 36 months, and 4 were between 37 and 45 months. The BTX-A injections occurred an average of months after the initial migration percentage measurement (range, 1 6mo), and the total time between initial and post BTX-A migration percentage measurements was months (range, 3 13mo). Patient Sex Age MP Table 1: Clinical Characteristics and Migration Percentages Age MP MP* Interval BTX-A Age RMP RMP Change LMP LMP Change 1 M M F M F M M M M M F F F M M M Abbreviations: F, female; L, left; M, male; R, right. *The migration percentage interval is the number of months between measurements of the initial migration percentage and the post BTX-A migration percentage. BTX-A age is the age at which the therapeutic BTX-A was given. Change is the initial migration percentage minus the post BTX-A migration percentage. A positive number means improvement and a negative number indicates worsening.

3 HIP MIGRATION PERCENTAGE AND BTX-A, Pidcock 433 Table 2: Clinical Subgroups Assorted by the Migration Percentage MP 10% Change 10% Improvement 10% Worse Totals Assorted by the Age at Which the Migration Percentage Was Measured Age of MP 10% Change 10% Improvement 10% Worse Totals Radiographic Findings Nineteen of the 32 hips in this report had an initial migration percentage (MP) less than 30% (low MP group) and 13 hips started with migration percentage of 30% or more (high MP group) (tables 1, 2). Eighteen of the 32 hip radiographs were in children 24 months or younger and 14 were in children older than 24 months. Ten right hips and 9 left hips were assigned to the low MP group. Six right hips and 7 left hips were included in the high MP group. Chi-square analysis revealed a statistically equivalent ratio of the number of patients in the low and the high MP groups for the left and the right hip chi square (P.28). The initial migration percentage was 22% 14% (range, 0% 58%) for the left hips and 25% 19% (range, 0% 47%) for the right hips. A change score was computed by subtracting the post BTX-A migration percentage measurement from the initial migration percentage (see table 1). Positive numbers reflect greater improvement (ie, decreases in the migration percentage), whereas negative numbers reflect worsening of the condition (ie, increases in the migration percentage). There was an average of 0.2% 12.4% change for the right hip migration percentage (range, 25% to 18%) and 2.4% 13.8% change for the left hip migration percentage (range, 25% to 20%), suggesting that there was no substantial improvement in migration percentage scores as a function of BTX-A injection for either hip when looking at overall group averages. A comparison of group means for gender revealed no significant difference for post BTX-A migration percentage change (t.31, P.75). The post BTX-A migration percentage was more than 10% lower in 4 of 8 hips in subjects with diplegic CP and in 3 of 24 hips in tetraplegic CP. An increase of more than 10% after BTX-A injection occurred in 2 of 8 hips in the diplegic group and in 6 of 24 hips in the tetraplegic group. A change in migration percentage of 10% or less, reflecting no significant change, was measured in 2 hips in the diplegic group and in 15 hips in the tetraplegic group. Analysis of Subgroups Two clinical variables of interest, initial migration percentage measurement and age at time of initial migration percentage measurement (initial migration percentage age), were examined to determine which types of patients improved after BTX-A injections (table 2). A 2 2 analysis of variance was calculated with post BTX-A migration percentage change as the dependent variable and initial migration percentage (2 levels: 30% and 30%) and initial migration percentage age (2 levels: 24mo and 24mo of age) as fixed factors. There was a significant main effect for initial migration percentage (F 19.05, P.001) and a significant interaction between initial migration percentage and initial migration percentage age (F 7.5, P.01). There was no significant effect for the age at which the initial migration percentage was measured (initial migration percentage age) (F.95, P.34). Comparison of group means for the 2 levels of the initial migration percentage revealed substantial differences between the 2 groups. Those patients with an initial migration percentage of 30% or more had the most substantial improvements, averaging 8.07% in the initial migration percentage change score compared with 7.73% in patients with less than a 30% initial migration percentage (t 4.2, P.001). Patients who were 24 months or older averaged 0.86% change in migration percentage compared with 3.0% in the group less than 24 months of age (t.83, P.41). A graphic representation of these findings is in figure 2. Adverse Events No significant adverse effects were reported. DISCUSSION Although the overall average change in migration percentage after BTX-A treatment was not significant, analysis of the initial migration percentage and the age when the initial mi- Fig 2. The migration percentage change is associated with the 2 independent variables: (1) the initial migration percentage and (2) age when the initial migration percentage was measured. Subjects who were younger than 24 months had a greater mean migration percentage improvement than subjects over the age of 24 months when the initial migration percentage was more than 30%.

4 434 HIP MIGRATION PERCENTAGE AND BTX-A, Pidcock gration percentage was measured revealed that certain types of patients might receive benefit from the intervention. These patients appear to be in the younger age group ( 24mo) with greater initial hip subluxation (migration percentage 30%). Of the 32 analyzed hips, 18 appeared to be stable over the study period, with a change of 10% or less in migration percentage. The main clinical variables of interest, initial migration percentage and age of initial migration percentage, were chosen because of their relevance to clinical practice. Migration percentages of 30% or more have been associated with progressive hip subluxation and the need for surgical treatment. 1,5 Almost all children with a migration percentage of 33% or more on 30-month hip radiographs in the series reported by Scrutton et al 5 needed treatment by the age of 5 years. At 24 months, many of these children are receiving intensive physical therapy with the goal of weight bearing and eventual ambulation. Concerns about the hip are usually raised at this time. In the group of 19 hips that had an initial migration percentage less than 30%, none showed a clinically significant ( 10%) improvement in migration percentage after BTX-A injection. Six of the 8 hips that were in the lowest initial migration percentage category of 10% or less showed a clinically significant increase ( 10%) in migration percentage after BTX-A treatment. Bracing or other postural treatments, such as stretching and positioning, may be better options for these children with minimal subluxation (ie, a migration percentage of 10%). When the migration percentage increases more than 10%, the addition of BTX-A to the overall therapeutic program may help stabilize hip position in conjunction with the other interventions. Only 1 of 11 hips with an initial migration percentage 11% to 29% had an increase of migration percentage of more than 10% after BTX-A injection. The hips with a 30% or more initial migration percentage appeared to have the most benefit from BTX-A treatments. Of the 13 hips in this group, 12 either showed a 10% or less change in migration percentage or a 10% or more decrease in migration percentage after BTX-A treatment. We postulate that this finding is related to increased ability to comply with a hip stabilization program. The age when the initial migration percentage was measured follows a similar pattern, because migration percentage increases with age. 5 The largest group of patients were treated between 13 and 24 months, which is the expected time when concern is greatest about the stability of the hips. In this age range, the effects of the BTX-A were evenly divided, showing 6 hips with a 10% or less change in migration percentage, 4 with a decrease of more than 10% in migration percentage, and 4 with an increase of more than 10% in migration percentage after BTX-A. Differences in the underlying pathology and variability with therapy compliance most likely account for this finding. In the group of patients over the age of 24 months, the migration percentage after BTX-A injection was either less than or equal to 10% or decreased by more than 10% in 13 or 14 hips, suggesting stabilization of subluxation. These findings suggest that improvement in migration percentage is a function of initial migration percentage and an interaction with the age at which the initial migration percentage was measured. Patients who had an initial migration percentage of 30% or more appeared to have more positive outcomes as evidenced by a decrease in the post BTX-A migration percentage. Further, patients who were younger than 24 months and had an initial migration percentage of more than 30% were more likely to have a decrease in post BTX-A migration percentage compared with patients older than 24 months and a migration percentage more than 30%. Table 3: Percentage of Hips With Migration Percentage Measured at Age 30 Months Needing Treatment by Age 5 Years MP Range on 30-Month Radiograph Hips Needing Treatment Reprinted with permission. Adapted from Scrutton et al. 5 In the 2 children under 15 months of age who were treated, the migration percentage of 3 of the 4 hips increased more than 10%, with 1 of the 4 increasing by a migration percentage of more than 30%. Treatment was based on the clinical assessment that the hips in these children were at high risk for progressive worsening. The increase in migration percentage despite BTX-A treatment in this younger group may be related to a predisposing factor that influences early hip development and subsequent dysplasia. 5 Although the subjects with diplegic CP had better outcomes than those with tetraplegic forms of CP on average, the small number of cases analyzed makes it difficult to draw any conclusions. Further studies of larger numbers of hips will be needed to determine the effects of CP subtype of hip migration percentage after BTX-A treatments. The standard protocol for the patients included in this study was to use nocturnal hip abduction orthoses. Information on compliance with their use was not collected and therefore is not available in this retrospective analysis. Because a decrease in migration percentage of more than 10% or a change in migration percentage of 10% or less was measured in 75% of the hips, a beneficial or stabilizing effect in the majority of hips was noted regardless of the compliance with bracing. We suspect that compliance may not have been as consistent in the group under 24 months and with the migration percentage of less than 30% because of the reassuring radiographic findings. This factor may be one reason for the greater number of hips that showed an increase in migration percentage in the younger group. In those patients in whom antispasticity medication was used, the dose was either unchanged or adjusted by such a small amount during the study period that we believe it did not affect the post BTX-A migration percentage. The maximal migration percentage that correlates with either decreased need for corrective orthopedic surgery or better outcomes after surgery for treating spastic hip disease varies from study to study; however, it appears to be 50% or less. In a long-term follow-up of hip subluxation in children with CP, Bagg et al 15 reported that untreated spastic hips with a migration percentage of less than 50% were more likely to reduce spontaneously or remain subluxed without progression to dislocation than hips with a migration percentage of more than 50%. In the series on bilateral hip dysplasia reported by Scrutton et al, 5 hip radiographs were obtained at 18, 24, 30, 48, and 60 months of age. They found that no hip needed treatment by the age of 5 years if the migration percentage at 30 months was less than 7%. The percentage of hips requiring surgery by 5 years increased as the migration percentage measured at 30 months increased (table 3). In children whose migration percentage was 33% or more at 30 months, 82% to 100% of those hips needed treatment by 5 years. Cornell et al 16 reported that the presurgical migration percentage was the best predictor for satisfactory surgical results. Eighty-three percent of hips with a

5 HIP MIGRATION PERCENTAGE AND BTX-A, Pidcock 435 presurgical migration percentage of less than 40% did well and all hips with a preoperative migration percentage of more than 60% had an unsatisfactory result. Limiting the migration percentage to less than 30% by 3 years in these children with CP appears to an important goal with respect to optimal orthopedic management. A study by Boyd et al 17 looked at the effects of BTX-A combined with hip bracing over a 3-year period using a randomized design with allocation to either a BTX-A with bracing group or observation-only group. At 3-year follow-up, 73% of the BTX-A group had not progressed to surgery, whereas only 53% in the observation-only group had not required surgery. Despite the small sample size of the present study, with only 32 hips analyzed, significant relationships emerged, suggesting that treatment with BTX-A may have a beneficial effect for some patients. The inherent variability of CP, variations in quality and amount of therapies, and variation in the injection of BTX-A related to dosage, location, and injector technique require that these results be interpreted with attention to the overall context of each case. Additional studies will be needed to look at the combined effects of bracing, antispasticity medications, and BTX-A over a longer period of time and should involve multiple BTX-A treatments as part of an ongoing hip protection program. CONCLUSIONS This analysis of a single BTX-A treatment in hips at risk for progressive subluxation suggests that the amount of subluxation indicated by the migration percentage and the age when the initial migration percentage is measured are factors that affect the posttreatment radiologic appearance of the hip. Multiple BTX-A treatments, the effects of bracing, and the likelihood of surgical intervention after BTX-A treatment were not evaluated. The variability of the underlying condition and vagaries in the technique of administering BTX-A necessitates individual consideration of circumstances surrounding each case when making decisions about intervention. References 1. Miller F, Bagg MR. Age and migration percentage as risk factors for progression in spastic hip disease. Dev Med Child Neurol 1995;37: Smith JT, Stevens PM. Combined adductor transfer, iliopsoas release, and proximal hamstring release in cerebral palsy. J Pediatr Orthop 1989;9: Hoffer MM. Management of hip in cerebral palsy. J Bone Joint Surg Am 1986;68: Boyd RN, Dobson F, Parrott J, et al. The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial. Eur J Neurol 2001; 8(Suppl 5): Scrutton D, Baird G, Smeeton N. Hip dysplasia in bilateral cerebral palsy: incidence and natural history in children aged 18 months to 5 years. Dev Med Child Neurol 2001;43: Reimers J. The stability of the hip in children. A radiological study of the results of muscle surgery in cerebral palsy. Acta Orthop Scand 1980;184(Suppl): Kalen V, Bleck EE. Prevention of spastic paralytic dislocation of the hip. Dev Med Child Neurol 1985;27: Harris NH, Lloyd-Roberts GC, Gallien R. Acetabular development in congenital dislocation of the hip with special reference to the indications for acetabuloplasty and pelvic or femoral realignment osteotomy. J Bone Joint Surg Br 1975;57: Heinen F, Linder M, Mall V, Kirschner J, Korinthenberg R. Adductor spasticity in children with cerebral palsy and treatment with botulinum toxin A: the parent s view of functional outcome. Eur J Neurol 1999;6(Suppl 4): Poutney T, Green E, Gard P, Many A, Nelham R. Retrospective analysis of hip migration in cerebral palsy [abstract]. Dev Med Child Neurol 2001;42(Suppl 85): Cosgrove AP, Corry IS, Graham HK. Botulinum toxin in the management of the lower limb in cerebral palsy. Dev Med Child Neurol 1994;36: Singh B. Use of botulinum toxin for adductor spasticity in cerebral palsy [abstract]. Ann Neurol 1994;36: Cooke PH, Cole WG, Carey RP. Dislocation of the hip in cerebral palsy. Natural history and predictability. J Bone Joint Surg Br 1989;71: Lespargot A, Renaudin E, Khouri N, Robert M. Extensibility of hip adductors in children with cerebral palsy. Dev Med Child Neurol 1994;36: Bagg MR, Farber J, Miller F. Long-term follow-up of hip subluxation in cerebral palsy patients. J Pediatr Orthop 1993;13: Cornell MS, Hatrick NC, Boyd R, Baird G, Spencer JD. The hip in children with cerebral palsy: predicting the outcome of soft tissue surgery. Clin Orthop 1997;Jul(340): Boyd R, Graham HK, Nattrass G, et al. Botulinum toxin A (BTX-A) combined with hip bracing delays the need for surgery in children with bilateral cerebral palsy: a randomized clinical trial and survivorship analysis [abstract]. Dev Med Child Neurol 2003; 45(Suppl 96):10.