Anterior cruciate ligament injury in paediatric and adolescent patients: a review of basic science and clinical research

Anterior cruciate ligament (ACL) injuries are recognised with greater frequency in children and adolescents. Non-operative treatment of ACL injuries in children may lead to knee instability and secondary injuries, especially in those who return to sports. ACL reconstruction is controversial in skeletally immature patients because of potential damage to the proximal tibial and distal femoral physes, which may lead to premature arrest and/or leg length discrepancies. This paper reviews studies of ACL injuries in children and adolescents, and examines basic science and clinical studies concerning physeal arrest secondary to ACL reconstruction tunnels. Some animal studies support the conclusion that ACL reconstructions in children have the potential to cause growth disturbances, and there are reports of growth plate complications due to ACL reconstruction in skeletally immature patients. There is evidence that ACL reconstruction can be performed in select skeletally immature patients, but the risk of growth plate complications must be considered.     

The tibial attachment of the anterior cruciate ligament in children and adolescents: analysis of magnetic resonance imaging

Recent studies have demonstrated that skeletally immature athletes with an ACL injury may require surgical reconstruction if they return to high-demand sports. This study used MRI to compare the anatomy of the ACL in skeletally immature and adult subjects. Measurements were recorded in the sagittal plane for the anterior-posterior dimension of the proximal tibia, and the anterior, center, and posterior limits of the ACL, and the roof inclination angle of the femur. These values were compared to established reference values for adult knee anatomy. In skeletally immature women ( n=7) the ACL anterior limit, center and posterior limit, and roof inclination angle were 28%, 46%, 63%, and 38 degrees, respectively, compared to 28%, 44%, 60%, and 35 degrees in adult women. In skeletally immature men ( n=15) the ACL anterior limit, center, posterior limit, and roof inclination angle were 27%, 43%, 59%, and 40 degrees, respectively, compared to 28%, 44%, 59%, and 37 degrees in adult men. In the younger subjects the overall dimensions of the proximal tibia were smaller than that in adults, but the anatomical landmarks for the ACL were proportional. If ACL reconstruction is performed in skeletally immature subjects, the smaller dimensions of the tibia need to be considered, and the use of anatomical landmarks is an important factor in graft placement     

Radiology of postnatal skeletal development

Initially the distal tibial physis is a relatively transverse structure. As the epiphysis matures, undulations develop within the physis and lappet formation occurs peripherally. Within the first two years a significant physeal undulation develops anteriorly above the medial malleolus. This undulation must not be misinterpreted as premature epiphyseodesis following distal tibial fracture. Secondary ossification in the distal tibia begins centrally and initially expands to fill the area over the tibial plafond. At the lateral side of the tibial epiphysis the ossification center may be wedgeshaped. The medial margin adjacent to the medial malleolus is often irregular and may show small peripheral foci of ossification. By seven to eight vears, the secondary center extends into the medial malleolus, with complete distal extension often not occurring until adolescence (although usually complete by ten to eleven years). The malleolar tip may exhibit an accessory ossification center. However, this center also may be a traumatic avulsion in the symptomatic patient. Physiologic epiphyseodesis begins over the medial malleolus and subsequently extends laterally. This pattern of closure appears to predispose to fracture of the lateral portion of the distal tibial epiphysis (fracture of Tillaux), as well as to triplane fractures. The articular surface curves onto the lateral side of the distal tibia to form an articulation with the lateral malleolus (distal tibiofibular joint). A similar extension occurs along the medial side of the fibula. These surfaces extend proximally as a recess to the level of the distal tibial physis, at which point the syndesmosis begins. The initially transverse distal fibular physis becomes a convoluted structure, with extensive peripheral lappet formation. Within these regions of physeal overlap there may be small areas of accessory ossification (both medially and laterally) that should not be misinterpreted as fractures. This overlapping also minimizes specific physeal separation and displacement (especially when compared to the incidence of distal tibial physeal injuries). Stress views may be necessary to show such an undisplaced fracture. The fibular physis normally is level with the tibial articular surface or distal extent of the tibial ossification center, especially after the second year of life (however, it may be more proximal in infants). As in the medial malleolus, there may be accessory ossification at the tip of the fibula. While this usually is a normal variant of secondary ossification, occasionally it also may result from trauma. Extensive porosity of the distal fibular metaphysis predisposes to buckling or torus injuries that may have severe, multiangular deformation.     

Intraorgan biodistribution and dosimetry of 153Sm-ethylenediaminetetramethylene phosphonate in juvenile rabbit tibia: implications for targeted radiotherapy of osteosarcoma.

Targeted radiotherapy using 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) is currently under investigation for treatment of primary osteosarcoma. Human osteosarcoma most frequently occurs in skeletally immature individuals, and previous studies in a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage might occur as a result of systemic 153Sm-EDTMP therapy. The aim of this study was to determine the distribution of 153Sm-EDTMP within the tibias of juvenile rabbits and estimate the radiation-absorbed doses delivered to the physeal cartilage. METHODS: Eight-week-old New Zealand White rabbits were injected intravenously with 7.57 kBq (280 microCi) of 153Sm-EDTMP. At 21 h after injection, the biodistribution of 153Sm in the epiphysis, metaphysis, diaphysis, and red marrow of the tibia was obtained. Two-dimensional digital autoradiography was performed on 2-mm sections of tibias for qualitative comparison with the biodistribution data. Self-tissue and cross-tissue absorbed doses were calculated using absorbed fractions generated by the Monte Carlo particle transport code MCNP-4C. RESULTS: The highest uptakes (percentage injected dose per gram [%ID/g] of tissue) of 153Sm, 1.99-2.56 %ID/g, were found in the proximal and distal metaphyses, 70%-73% of which localized within 3 mm of the physeal cartilage. The second highest tissues of uptake were the proximal and distal epiphyses, at 0.33-0.62%ID/g. Digital autoradiography imaging confirmed that the majority of 153Sm deposited in the tibia localized to these tissues. Radiation-absorbed doses to the proximal and distal metaphyses were 183 and 130 mGy/MBq, respectively, and those to the proximal and distal epiphyses were 141 and 43.4 mGy/MBq, respectively. These tissues represented the only source compartments contributing to the physeal cartilage doses of 50.0 mGy/MBq for the proximal physis and 39.2 mGy/MBq for the distal physis. CONCLUSION: The 153Sm absorbed doses to the physeal cartilage were consistent with values that can cause dose-limiting damage to rapidly proliferating and differentiating chondrocytes. The pronounced uptake in the juvenile epiphysis indicates that the proliferating zone of the physis can be irradiated from multiple areas, which could increase the expression and degree of radiation damage. Further investigation of the effects of 153Sm-EDTMP on immature physeal cartilage is warranted to develop optimized treatment regimens.     

Epiphyseal and physeal injury: comparison of conventional radiography and magnetic resonance imaging

PurposeTo compare conventional radiography and magnetic resonance imaging (MRI) in the assessment of epiphyseal and physeal injury.Materials and methodsSeventeen cases with epiphyseal and physeal injury were examined with conventional radiography and MRI. Two blinded experienced radiologists separately evaluated the results retrospectively.ResultsTwo Salter–Harris II fractures showed displacement of epiphysis and metaphyseal fragment, as well as T1 hypointensity and T2 hyperintensity in the physis on MRI. Three Salter–Harris IV fractures showed a fracture line in the epiphysis and metaphysis on two modalities, as well as linear T2 hyperintensity in the physis. All five slipped epiphysis showed signal intensity abnormality in the physis on MRI aside from the physeal widening and epiphyseal displacement seen on radiographs. Seven patients with bony bridge formation showed premature closure of the physis, shortening, and remodeling of the end of bones involved.ConclusionsConventional radiography and MRI are both useful in the diagnosis of epiphyseal and physeal injury. MRI can provide more detailed information, which could direct treatment planning and prognosis predicting.     

The relationship of the femoral origin of the anterior cruciate ligament and the distal femoral physeal plate in the skeletally immature knee. An anatomic study.

We defined the anatomic relationship of the anterior cruciate ligament femoral origin to the distal femoral physis in the skeletally immature knee with use of 12 fresh-frozen human fetal specimens (ages, 20 to 36 weeks). Each specimen underwent magnetic resonance imaging, was dissected free of soft tissue, sectioned in the sagittal plane, and stained. The spatial relationship of 1) the epiphyseal side of the physeal proliferative zone to the nearest point of bony attachment of the anterior cruciate ligament and 2) the origin of the anterior cruciate ligament to the over-the-top position were measured. The same measurements were made in 13 skeletally immature knees (ages, 5 to 15 years). We found that the femoral origin of the fetal anterior cruciate ligament developed as a confluence of ligament fibers with periosteum at 20 weeks, vascular invasion into the epiphysis at 24 weeks, and establishment of a secure epiphyseal attachment by 36 weeks. In the fetus, the distance from the anterior cruciate ligament femoral origin to the epiphysis was 2.66+/-0.18 mm (range, 2.34 to 2.94). There was no significant change in this distance in adolescent specimens (2.92+/-0.68 mm; range, 2.24 to 3.62). The over-the-top position was at the level of the distal femoral physis.     

Rupture of the anterior cruciate ligament in children: early reconstruction with open physes or delayed reconstruction to skeletal maturity?

The purpose of this study was to compare two different strategies of management for ACL rupture in skeletally immature patient. In group 1, patients were treated in a children hospital by ACL reconstruction with open physis. In group 2, patients were treated in an adult hospital by delayed reconstruction at skeletal maturity assessed radiologically. Fifty-six consecutive patients were included in this retrospective study. Mean time from injury to surgery in group 1 and 2 was, respectively, 13.5 and 30 months. Patients from group 2 exhibited a higher rate of medial meniscal tears (41%) compare to group 1 (16%) and higher rate of meniscectomy. Both groups had the same rate of lateral meniscal tears. A temporary tibial valgus deformity was reported which was subsequently spontaneously resolved. No definitive growth disturbance was noticed. At 27 months mean follow-up, a best subjective IKDC score was found in group 1. Objective IKDC and radiological results were similar in both groups. Early ACL reconstruction is therefore a recommended option.     

Electrical injury involving the immature skeleton

Two patients are presented with significant problems of skeletal development and function consequent to electrical impulse propagation through the immature skeleton. Amputation stump revision in the first case allowed an opportunity to assess specific histologic and morphologic changes. Electrical damage completely destroyed portions of trabecular bone in the metaphyses and epiphyseal ossification centers. There were morphologic irregularities in the physis of the distal femur, while in the proximal tibia complete cessation of growth occurred through presumed electrical ablation of the physis. There was virtually no endosteal or periosteal callus, no intertrabecular inflammatory response, and no new bone formation well over a year following the original injury. The knee joint exhibited severe fibrous ankylosis. In the second case localized arrest of the posterolateral portion of the proximal tibial physis caused a valgus/recurvatum deformation, and probably slowed down distal growth sufficiently in the stump end to prevent irregular terminal overgrowth of the tibia, although it did occur in the fibula.     

Anterior cruciate ligament injury in the skeletally immature athlete

The incidence and prevalence of anterior cruciate ligament (ACL) injury in the school-age athlete is unknown, but ACL injury is certainly not a rarity, especially in girls involved with soccer and basketball. Clinical examinations provide a high degree of specificity and accuracy for the diagnosis. Clinical evaluation includes the determination of physiologic maturity, which is then entered as a factor in the treatment algorithm. Nonsurgical treatment may be definitive or used as a temporizing measure until skeletal maturity. It must include counselling about sports modification to prevent further intra-articular damage. Concerns exist about surgical intervention, which may produce deformity sequelae from physeal invasion. Patients with concommitant unstable meniscal tears require ACL reconstruction. Three types of surgical reconstruction are possible, based on the amount of physeal transgression: physeal sparing, partial physeal, and complete physeal. Treatment decisions must take into account the patient's anatomic and physiological assets and liabilities, and decisions must be made on an individual basis. Promising results have been reported with ACL reconstruction in truly skeletally immature patients, but the number of cases are small and the follow-up is relatively brief.     

Preoperative evaluation and anterior cruciate ligament reconstruction technique for skeletally immature patients in Tanner stages 2 and 3

BACKGROUND: Transphyseal anterior cruciate ligament reconstruction in skeletally immature patients carries the risk of adverse sequelae. PURPOSE: 1) To provide clinical and radiographic methods to identify skeletally immature patients with significant remaining lower limb growth. 2) To provide a method for calculating the percent area lesion created by a 6-mm distal femoral physeal tunnel. 3) To present a method of partial transphyseal intraarticular anterior cruciate ligament reconstruction with bipolar graft fixation in these patients. 4) To report on clinical, functional, and radiographic results at skeletal maturity. METHODS: Fourteen adolescents with symptomatic anterior cruciate ligament instability who were identified as being in Tanner stages 2 and 3 underwent partial transphyseal intraarticular anterior cruciate ligament reconstruction with the use of hamstring tendon grafts (transphyseal only in the femur and through the epiphysis in the tibia). RESULTS: At skeletal maturity, 10 patients were asymptomatic and fully active in sports. No patient had significant leg-length inequality or angular deformity after use of a 6-mm femoral physeal tunnel, which represented 1) less than 7% of the frontal plane and 2) less than 1% of the transverse plane cross-sectional femoral physeal areas. CONCLUSIONS: The choice of the exposed technique and the method used to select patients permitted us to avoid adverse sequelae.     

Proximal anterior cruciate ligament avulsion fracture in a skeletally immature athlete: a case report and method of physeal sparing repair

Traumatic rupture of the anterior cruciate ligament (ACL) in adulthood is relatively common and surgical reconstruction is frequently required to allow return to high-level activities. There is growing evidence to suggest that ACL rupture in children is more common than previously thought and a poor outcome is associated with conservative management. The site of rupture in childhood is predominantly tibial avulsion, but mid-substance tears have also been reported. We report a case of a proximal ACL avulsion in an 11-year-old athlete and discuss a method of extra-physeal repair. There are very few previous reports of proximal avulsion fractures in skeletally immature patients.     

Age-related vascular changes in the epiphysis, physis, and metaphysis: normal findings on gadolinium-enhanced MRI of piglets

OBJECTIVE: We sought to study the normal enhancement patterns seen on MRIs of the epiphysis, physis, and metaphysis and age-related vascular changes in piglets using gadoteridol, a nonionic gadolinium chelate. MATERIALS AND METHODS: We quantitatively and qualitatively analyzed the normal changes on sequential T1-weighted images after the IV administration of gadoteridol. In an investigation approved by the research animal care committee at our hospital, we studied the proximal and distal femurs of 26 piglets 1-6 weeks old and correlated the enhanced images with findings on intermediate-weighted, T2-weighted, and gradient-recalled echo images and at histologic examination. RESULTS: We observed early enhancement of the epiphyseal vascular canals, the main physis, the physis of the secondary ossification center, and a metaphyseal band adjacent to the physis. Enhancement of the epiphyseal and metaphyseal marrow and of the epiphyseal cartilage was slower. In the epiphyseal cartilage, we saw three phases of enhancement: vascular, canalicular, and cartilaginous. As the piglets matured, enhancement of the epiphyseal cartilage decreased, and the epiphyseal vascular canals were less conspicuous. Physeal enhancement was greatest during the first week of life, declined at 3 weeks, and subsequently increased again as the physis came to lie adjacent to a larger segment of the epiphyseal ossification center. CONCLUSION: Gadoteridol-enhanced MRIs showed multiple cartilaginous and vascular structures of the growing skeleton. With maturity and progressive epiphyseal ossification, epiphyseal cartilage enhancement decreased, and physeal cartilage enhancement increased.     

Ankle injuries in the young athlete

Ankle injuries in the young athlete are quite different from those of an adult. Because the epiphyseal plates of the distal tibia and fibula are significantly weaker than surrounding ligaments, failure on stress occurs through the growth plates rather than through soft tissue. Growth-plate injuries can assume a distinct pattern based on the maturity of the physis. Leg length inequality and angular deformity are potential sequelae from significant injury to the ankle in the skeletally immature but, fortunately, occur infrequently. Soft-tissue injuries about the ankle are rare, but with advanced, rigorous training techniques a new pattern of overuse injuries appears to be emerging.     

Posterior distal femoral and proximal tibial metaphyseal stripes at MR imaging in children and young adults

PURPOSE: To determine the frequency and distribution of the hyperintense stripe seen along the posterior surface of distal femoral and proximal tibial metaphyses at magnetic resonance (MR) imaging. MATERIALS AND METHODS: One hundred forty-two MR imaging studies obtained in 139 children and young adults were reviewed. The authors recorded the presence and distribution of posterior distal femoral and proximal tibial metaphyseal stripes. Presence of stripe was correlated with patient age and sex and with patency of the adjacent physis. Fifty-nine studies of adults were reviewed similarly. Two-way analysis of variance was performed to compare mean patient age for sex among four different categories that were based on stripe presence and physeal patency. Orthogonal contrasts were used to determine whether a linear trend across the categories existed. In one cadaveric femur, imaging and histologic analysis were performed. RESULTS: A metaphyseal stripe was seen in all patients with a completely or partially open physis (110 femora, 102 tibiae) and in 56 femora and 60 tibiae in the patients with fused physes. Thirty-five femora and 35 tibiae showed no stripe; all patients were skeletally mature. Correlations between metaphyseal stripe visualization and physeal patency were significant (P <.001). Differences in mean patient age among the four categories were significant for both (femoral and tibial) locations (P <.001), and a linear trend with age (P <.001) was demonstrated. This linear trend was also observed in both sexes (P <.001). Histologic analysis revealed highly vascular loose fibrous tissue. CONCLUSION: A posterior metaphyseal stripe is seen at MR imaging of the skeletally immature knee and likely reflects normal bone growth.     

Concomitant physeal fractures of the distal femur and proximal tibia

Concomitant physeal fractures of the distal femur and proximal tibia are very rare in children and adolescents. They are included in the classification of the floating knee injuries. Two cases with this combined injury are reported. They were closed injuries and in both patients the fracture of the proximal tibial epiphyseal plate was nondisplaced. In the first, a six-year-old girl, an early diagnosis was made radiographically. The intra-articular femoral fracture was operatively reduced and fixed. No growth abnormality was encountered 12 years later. The second patient, a 16-year-old boy, was conservatively treated for a displaced fracture-separation of the distal femoral epiphysis. Four weeks later there was physeal widening on both sides of the knee which indicated an associated fracture of the proximal tibial epiphyseal plate. One year after injury there was a varus deformity of the knee that was treated with a corrective osteotomy. Ten years later there is normal alignment of the leg.     

Anterior cruciate ligament reconstruction in adolescents with open physes

The purpose of this study was to evaluate anterior cruciate ligament reconstructions performed in adolescents with open physes and a skeletal age of at least 14 years. At one center, from 1992 to 1996, 19 adolescents (ages, 11 to 15 years) with open physes and a skeletal age of at least 14 years underwent arthroscopic anterior cruciate ligament reconstruction using an Achilles tendon allograft placed through drill holes across the open physes in both the distal femur and proximal tibia. Fifteen patients returned for reevaluation at an average of 25 months postoperatively (range, 12 to 60 months); the remaining four patients were interviewed by telephone. There were no significant leg-length discrepancies or angular deformities as determined by scanograms and anteroposterior and lateral radiographs of the femur and tibia. The mean Lysholm knee score was 97 (range, 94 to 100) and the mean KT-1000 arthrometer side-to-side difference at 20 pounds of anterior force was 1.7 mm (range, 0.0 to 3.0). All patients were satisfied with the results of surgery, and 16 of 19 patients returned to the same sport they were participating in before the injury. This study demonstrates that anterior cruciate ligament reconstruction using an Achilles tendon allograft is a viable treatment option for skeletally immature patients with a skeletal age of 14 years who have sustained midsubstance tears of the anterior cruciate ligament.     

The anterior tilt angle of the proximal tibia epiphyseal plate: A significant radiological finding in young children with trampoline fractures

Objective

Evaluation of the anterior tilt angle of the proximal tibia epiphyseal plate in young children, which suffered a trampoline fracture in comparison with a normal population.

Materials and methods

62 children (31 females, 31 males) between 2 and 5 years of age (average 2 years 11 months, standard deviation 11 months) with radiographs in two views of the tibia were included in this retrospective study. 25 children with proximal tibia fractures were injured with a history of jumping on a trampoline. All other causes for tibia fractures were excluded. A normal age-mapped control cohort of 37 children was compared. These children had neither evidence of a trampoline related injury nor a fracture of the tibia. The anterior tilt angle of the epiphyseal plate of the tibia was defined as an angle between the proximal tibia physis and the distal tibia physis on a lateral view. Two radiologists evaluated all radiographs for fractures and measured the anterior tilt angle in consensus. An unpaired Student's t-test was used for statistical analysis (SPSS). Original reports were reviewed and compared with the radiological findings and follow-up radiographs.

Results

In the normal control group, the average anterior tilt angle measured −3.2°, SD ± 2.8°. The children with trampoline fractures showed an anterior tilt of +4.4°, SD ± 2.9°. The difference was statistically significant, P < 0.0001. In 6 patients (24% of all patients with confirmed fractures) the original report missed to diagnose the proximal tibial fracture.

Conclusion

Young children between 2 and 5 years of age are at risk for proximal tibia fractures while jumping on a trampoline. These fractures may be very subtle and difficult to detect on initial radiographs. Measurement of the anterior tilt angle of the proximal tibia epiphyseal plate on lateral radiographs is supportive for interpreting correctly trampoline fractures.     

Physeal widening in the knee due to stress injury in child athletes

OBJECTIVE: The objective of our study was to describe the MRI appearance of and possible mechanism responsible for physeal widening in the knees of high-level child athletes. CONCLUSION: Widened physes in the knees of skeletally immature child athletes have MR signal characteristics similar to the normal physis but likely are a sign of stress injury. These children should cease the offending sport and rest the knee to allow rapid healing.     

MRI of anterior cruciate ligament injuries and associated findings in the pediatric knee: changes with skeletal maturation

OBJECTIVE: The objective of our study was to evaluate the MRI characteristics of anterior cruciate ligament (ACL) injuries and associated findings relative to skeletal maturity. We also contrast the frequency of findings in this younger population to adult data. MATERIALS AND METHODS: Eighty-two consecutive knees with an MRI report diagnosis of ACL injury (partial tear, sprain, or complete tear) or tibial spine avulsion fracture imaged over 4 years were retrospectively reviewed. Patients were grouped by degree of skeletal maturity as determined from the MR images. The examinations were reviewed for the type of ACL injury, secondary imaging findings, and associated knee injuries. Findings were correlated to skeletal maturity, and frequencies were compared with adult data. RESULTS: ACL injuries were more common in boys in the skeletally immature group, but more common in girls in the skeletally mature group (p = 0.03). Tibial spine avulsion fractures were most common in skeletally immature patients (p < 0.01), whereas complete tears of the ACL were most common in skeletally mature patients. Associated injuries were less common in the skeletally immature group, but this trend did not reach statistical significance. Most secondary signs of ACL injuries occurred at similar rates in all groups with frequencies similar to those reported in adults. CONCLUSION: ACL injuries in skeletally immature patients are seen more often in boys. Tibial avulsion fractures and partial tears are more common in younger, less rigid skeletons that may absorb the forces of trauma. As children mature, complete ACL tears and associated injuries occur in frequencies approaching those patterns seen in adults. Similarly, skeletally mature girls are affected more often than mature boys.     

Radiology of postnatal skeletal development

The patella initially ossifies at between three and five years, commencing as multiple foci that rapidly coalesce. As the patellar ossification center enlarges the expanding margins may be irregular and associated with accessory ossification centers. These are most common superolaterally and may lead to the development of a bipartite patella. The bipartite patella has cartilaginous continuity despite the appearance of osseous discontinuity. The patella expands to all cartilaginous contours during late adolescence when the epiphyseal ossification centers around the knee are also in the final stages of maturation. The only cartilage not replaced is that occupying the superior twothirds of the articular surface (the lower one-third is covered by the fat pad). The subchondral plate does not assume the actual articular contours until the late stages of osseous maturation (after ten to twelve years). Accordingly, typical measurements such as medial and lateral angulation cannot be accurately done prior to the final stages of patellar ossification expansion and maturation.The tibial tuberosity begins ossification at between seven and nine years as a distal focus. This progressively enlarges proximally and anteriorly, while the main tibial ossification center concomitantly expands downward into the tuberosity. A section of epiphyseal cartilage usually remains between these two ossification centers until close to physeal maturity. The anterior chondro-osseous region at the site of patellar tendon attachment is a biomechanically susceptible region that may be acutely or chronically traumatized to create an Osgood-Schlatter lesion. The physis associated with the tibial tuberosity is histologically modified in a proximal to distal gradation of columnar adaptation to specific biomechanical demands in this region. Closure of the tuberosity physis occurs in a proximal to distal direction.