Joint contracture, especially flexion contracture in the lower limb, is one of the most common complications in the musculoskeletal system, aside from muscle weakness and atrophy, soft tissue changes, disuse osteoporosis, and degenerative joint disease following prolonged immobilization. It is commonly found when a patient is put in static positioning for a continuous length of time, such as in patients with wheelchair reliance or bedridden patients with chronic illness or acute critical illness. Besides, immobilization used as critical treatment in fractures, joint dislocations, and ligament injuries should also be considered [1,2,3,4]. This condition is consistent with our patient in whom immobilization is thought to be the main cause of contracture. Our patient was put in prolonged knee–chest positioning for almost 2.5 years, resulting in severe flexion contracture of bilateral hip, knee, and ankle joints. Pathological change is reported to begin after 2 weeks of immobilization, while more prolonged time is associated with more extensive contractures [16, 17]. Flexion contracture in the lower limb contributes significantly to disability in activities of daily living due to mobility limitation, decreased functional motor function, and reduced range of motion. Moreover, severe and chronic cases of this condition are associated with debilitating issues in which disease progression may affect not only the neuromusculoskeletal system but also other organ systems, especially respiratory, cardiovascular, and genitourinary [18,19,20].
The pathophysiology of joint contracture is multifactorial and immensely diverse. It involves both histopathological changes of the various neuromusculoskeletal structures and environmental factors. Negative alteration of healthy connective tissue is related to prolonged immobilization. Homeostasis of mechanical properties of the connective tissue and its function is disturbed with the loss of mechanical stimulation of the joint. Regarding the type of anatomical structures and tissues involved in the restriction of range of movement, muscles, tendons, fascia, capsule, ligaments, bone, cartilage, and skin may play significant roles. These tissues can be classified into two main structural components leading to joint contracture in immobilization, viz. myogenic and arthrogenic contracture components. Myogenic contracture plays an important role and becomes the principal component in the early stage. It involves mainly muscle, tendon, and fascia changes. Arthrogenic contracture, on the other hand, accounts for the later stage, in which changes are found across cartilage, joint capsule, bone, and ligament structures [21,22,23].
When a joint goes through continuous and prolonged immobilization, skeletal muscle will undergo disuse atrophy. Reduced cross-sectional area (CSA) and shortened muscle fiber were observed under the microscope. Besides, a decrease in muscle protein synthesis with enhancement of proteolysis has also been reported [24, 25]. This condition is associated with the catabolic phase, involving five main proteolytic pathways, including the ubiquitin–proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, autophagy–lysosomal pathway, and Ca2+-dependent pathway. With an immobilized muscle put in a shorter position, loss of sarcomere will be present as an adaptation to muscle functional length [24, 26]. In addition, fibrosis over the skeletal muscle tissue is also found as pathological changes affecting further progression of muscle contracture. There will be accumulation of fibrotic tissue in the perimysium, epimysium, and endomysium because of overexpression and overproduction of collagen, with type 1 primarily followed by type III collagen. Fibril arrangement will adapt to be more circumferential with shortening of muscle fibers. Changes with increased intramolecular and intermolecular cross-linking also restrain skeletal muscle extensibility. Besides, interleukin (IL)-1β and transforming growth factor (TGF)-β1 upregulation by macrophages with significantly higher level of protein and messenger RNA (mRNA) level of hypoxia inducible factor-1α (HIF-1α) expression is associated with fibroblast differentiation in immobilization-induced skeletal muscle fibrosis [24, 27, 28].
Previous studies have reported that ubiquitin–proteasome-dependent proteolysis and the caspase system pathway play a key part in the development of contracture regarding muscle atrophy in disuse skeletal muscle. This is indicated by overexpression and an increase in the amount of muscle atrophy F-box protein (MAFbx or atrogin-1) and muscle ring finger-1 protein (MuRF-1) as muscle-specific ubiquitin-protein ligase in muscle atrophy due to disuse of skeletal muscle in immobilization [29]. Besides, major signaling activators of MAFbx and MuRF-1, protein kinase B (Akt), insulin-like growth factor 1 (IGF-1), and phosphatidylinositol 3-kinase (PI3K) are increased prior to upregulation of MAFbx, MuRF-1, and other proapoptotic genes [30,31,32]. Inhibitor of nuclear factor kappa-B kinase (IKKβ/NF-κB) may also be an important pathway, specifically for MuRF-1 [33]. The use of MG132 as an inhibitor of the NF-κB pathway demonstrated decreased expression of MuRF-1 [34]. Eukaryotic translation initiation factor 3-f (eIF3-f) and myogenic differentiation (MyoD) become two main muscle regulatory factors targeted by muscle-specific E3s. EIF3-f and MyoD play an important role in activation of the proliferation and differentiation of myogenic satellite cells into myoblasts, which further fuse to form new muscle fibers [35,36,37]. In addition, the role of the ubiquitin–proteasome-dependent system in degeneration of myofibrillar protein works synergistically with the calpain system [38].
Regarding the caspase system, an increase in caspase-3 level is reported during immobilization. Caspase itself is a cysteine-rich enzyme that targets aspartic acid residue in specific protein. Caspase-3 showed a significant role in the initiation of muscle disuse atrophy through apoptosis and inflammatory processes [39, 40]. In disuse of skeletal muscle due to immobilization-induced joint contracture, tissue inhibitor of metalloproteinase (TIMP)-1 and -2, and other MMP pathway are associated with atrophy in remobilization. Their levels were increased by 30- and 2-fold, respectively, in immobilized anterior tibialis muscle at day 8 of observation and remained raised until day 5 of recovery. This is followed by increased MMP-2 and MMP-14 mRNA levels at days 1–9 of recovery [25, 41]. Regarding the autophagy–lysosomal pathway, lysosomal cathepsin will break down membrane proteins, together with receptors, ligands, and transporters. The level of the LC3-phosphatidylethanolamine conjugate (LC3-II)/cytosolic form of microtubule-associated protein light chain 3 (LC3-I) was observed to be higher in immobilized muscle. An increase in the value of this ratio was associated with increased autophagy–lysosomal activity, since LC3-II was mainly found in autophagosome membranes [42].
Within a later stage of prolonged immobilization, changes over arthrogenic structures may also account for further contracture progression. However, early changes are associated with proliferation of fibro-fatty tissue invading joint space. In a diarthrodial joint, the capsule plays a key role in limiting the range of motion. It is made of a densely fibrous structure, mainly composed of collagen protein. Fibrotic changes of the joint capsule with an increased level of type I collagen have been reported in immobilized limbs. Besides, a decreased level of glycosaminoglycan following collagen fiber disorganization will further result in a decreased water level and accumulation of collagen crosslinking. Other reported changes include decreased proliferation of synoviocytes with disruption over normal length of synovial intima [43, 44]. Genomic study and analysis have also reported upregulation of chondroadherin, angiogenic inducer CYR61, and SRY-box with decreased casein mRNA. These changes were found in tissue fibrosis over posterior capsule of patients with OA and contractures [43].
Other proposed mechanisms in regard to the induction of contracture in our patient are due to muscle weakness and spasticity following spinal trauma. We consider these mechanisms since our patient had a history of falling from a motorcycle in a road traffic accident 3 years ago and falling down in the bathroom in supine position 2.5 years ago, leading to a suspected spinal cord injury despite normal findings reported in radiological studies. This condition may be referred to the spinal cord injury without radiographic abnormality (SCIWORA) or spinal cord injury without radiographic evidence of trauma (SCIWORET) concept in which a patient with normal findings on plain radiographs and computed tomography (CT) scans may present with neuromuscular symptoms (sensory or motor deficit, or both). The difficulties in establishing the diagnosis are associated with its rarity and broad variety of symptoms. This condition presents commonly following a traumatic accident or degenerative process. Neuroimaging studies, especially using magnetic resonance imaging, allowed better visualization of damage and structural abnormality of spinal soft-tissue and intramedullary lesions [45, 46]. Nevertheless, microscopical changes with chronic disease progression in our patient also need to be considered and take into account, since confirmation using MRI studies reported normal findings.
The main mechanisms of primary injury result from impact, transient or complete compression, distraction, and laceration or transection, with impact together with preserved compression being the main form of injury [47, 48]. Further changes of secondary injury will follow during disease progression. This phase consists of vascular damage, ionic imbalance, neurotransmitter accumulation (excitotoxicity), free radical formation, calcium influx, lipid peroxidation, inflammation, edema, and necrotic cell death in the acute period. Apoptosis, demyelination of surviving axons, Wallerian degeneration, axonal die-back, matrix remodeling, and evolution of a glial scar occur thereafter in the subacute period. Furthermore, formation of a cystic cavity, progressive axonal die-back, and maturation of the glial scar will present in the chronic period throughout the injury site. Severity and location, and whether the lesion lies over the spinal cord completely or not, influence the clinical outcome of the patient [47].
Neurological impairments, presented as paraplegia, hemiplegia, tetraplegia, or muscle paralysis, are some of the most debilitating issues related to traumatic spinal injury. This condition may progress and have an impact on the emergence of other complications, especially related to the musculoskeletal system. Contracture of the extremities in traumatic paraplegic patients is a common finding. With muscle weakness due to spinal injury, there may be a disruption of balance and stability between agonist and antagonist muscles [47, 49, 50]. Lower-limb flexion contracture and equinovarus deformity are more susceptible to develop as the patient becomes weaker during progression of the disease and spends more time in the sitting position. Besides, denervation will further result in loss of contraction stimulation with size reduction and necrosis of muscle fibers. Muscle spasticity may also be associated with contracture progression development in the traumatic patient, whether it affects the brain or spinal cord structure, resulting in upper motor neuron lesions. Muscle stiffness and imbalance with deformed posture, increased binding between actin and myosin, increased connective tissue with decreased elasticity, and shortening of the myofibril due to sarcomere loss will follow the spastic contraction in the patient.
Psychological and social conditions also play a key role and become significant factors regarding disease progression in our patient. Health beliefs and expectations of the patient are associated with vulnerability to illness. Besides, the patient will adapt and behave to reduce the risk of illness in regard to his/her health beliefs and expectations, which develop throughout their life. Culturally determined health beliefs, which are still commonly found in society, especially in our case, in addition to formed individual perception, may influence coping behaviors regarding musculoskeletal problems [51]. Our patient comes from a family and society with low educational level. He had already opted for and preferred another form of traditional massage treatment before presenting to the healthcare facility. Moreover, the traditional medicine man also emphasized fear-avoidance beliefs, in which physical activity and work are associated with disability and pain deterioration [52].
This further influenced the beliefs of the patient, his family, and environment regarding his care. This concept can also be associated with kinesiophobia, defined as “excessive, irrational, and debilitating fear of physical movement and activity resulting from a feeling of vulnerability to painful injury or re-injury” [53]. When a patient is placed under prolonged rest and immobilization, this state of freedom from physical and mechanical stressors is believed to allow injuries to heal. However, as we know, movement and stretching stimulation are important to improve range of motion and prevent contracture formation. The presence of fear-avoidance beliefs becomes an indicator of poor prognosis and must be well managed. In the long term, this condition will trap the patient in a vicious cycle of increased fear of more pain and disability, which further causes worse disuse, disability, and depression [51, 54].
The social aspect, including social support, also has a significant impact on physical health in regard to recovery from musculoskeletal injury. More intimate and trusting relationships are associated with more beneficial effects of support, as suggested by the Convoy model. Better physical health and recovery were reported in individuals with strong support from family and friends. A closer, more intimate, and stable relationship is more convenient and beneficial for support. A lack of social support, whether that be no social circle, difficulty in accessing a support network, or a strong personal belief in independence that does not require social support, resulted in a higher complication rate and a hampered recovery process [55, 56]. Functional support from family members is mainly related to material and instrumental aid, while emotional support is more frequently provided by friends. However, we also need to emphasize patient personality traits influencing his/her beliefs regarding the need for and and perception of social support.
In our case, the patient’s condition was reported to have worsened following the treatment obtained from traditional massage therapy, with no improvement for almost 2.5 years. The patient and his family were put in jeopardy by pessimistic beliefs and low expectations about disease prognosis. The patient’s mother was the only family member to live with and care for him, yet she started to neglect him with the worsening of his condition at the end. No support was provided by the patient’s father or any other family members. Our patient has low socioeconomic status and lacks financial and psychosocial support. Furthermore, he lives in a rural area with difficult access to healthcare facilities, adequate infrastructure, and trained manpower. After 3 years of neglect of his condition, some of his neighbors who cared for and worried about the patient’s condition and prognosis finally asked a humanitarian and social aid institution for help to bring and refer him to our center at Cipto Mangunkusumo General Hospital to obtain the required treatment.
In severe cases of hip flexion contracture exceeding 90°, the patient and physician are faced with a difficult challenge with no fixed treatment protocol and other associated chronic complications, including pressure sores, hyperlordosis, or even scoliosis. Thorough and conscientious physiotherapy combined with surgery play an important role in the management of this condition [6]. Nicodemo et al. reported five cases of hip flexion contracture treated with either Girdlestone or replacement arthroplasty, or myoarthrolysis [57]. Besides, there were 12 proximal femoral resection procedures in children with spastic and painful hip dislocation and paraplegic flexion contracture [58]. Another proximal femoral resection procedure was reported by Bhattacharyya et al. regarding longstanding hip flexion contracture with flaccid paraplegia in a 20-year-old female student. Immediate straight hip joint with the ability to sit, lie on her back, and mobilization using a wheelchair was reported [6]. Myotomy across iliopsoas and obliquus externus showed good results. Hip replacement arthroplasty is another common procedure with satisfactory outcome. Complete extension of hip and knee with some of the patients returning to walking were obtained. However, high rates of recurrent dislocation of the hip, infection, implant loosening, blood loss, and osteoporosis of the bone are associated with hip replacement [59, 60].
Regarding knee flexion contracture with severe presentation, a combination of knee arthroplasty followed by serial casting and rehabilitative knee mobilization plays an important role in achieving a favorable outcome. However, residual flexion contracture of 7–10° was found, especially in severe cases with contracture greater than 80–90° [61, 62]. Additional distal femur resection and Z-plasty procedure over iliotibial tract and biceps tendon after knee arthroplasty may be needed in severe cases. Performing a Z-plasty procedure before knee arthroplasty is associated with a high rate of tibial dislocation [63]. Postsurgery serial casting or other orthotic management by gradual and controlled knee extension with regular continuous passive stretching resulted in increased range of movement. Besides, casting is preferred to be applied continuously for no longer than 5 weeks due to the increased stiffness and thermal injury complications [64]. Regarding nonoperative treatment, serial casting and wedging can extend the knee to a full range of extension [65, 66]. Moreover, contractures over the ankle region, whether plantar or dorsiflexion, with or without inversion or eversion of the soles, are commonly found in patients with central nervous system injury. The prevalence was reported to be as high as 57% in patients with spinal injuries [67]. Combined treatment to achieve terminal stretch may involve several methods of passive stretching, active ROM, antagonist strengthening, and release surgery. Compared with short duration with high tension strength, passive prolonged stretching is reported to have better outcome and efficacy. Adjustable dynamic orthoses provide good and effective results in the treatment of contractures. Besides, sustained stretch can also be achieved by using serial casting [68].
However, there are several factors one must consider before deciding on and performing surgery as the main management of contracture in such patients. First, residual muscle strength should be taken into account. With appropriate and adequate rehabilitative training, nerve and muscle can regain their functional capacity and strength through the preserved plasticity mechanism. We also need to evaluate whether there are marked changes of the density and characteristics of the bone. Loss of weight bearing and contraction with associated increased catabolic state result in osteoporosis. The rate of bone loss was reported to be 5–20 times higher compared with metabolic diseases. Rigorously intensive postoperative rehabilitation combined with muscle imbalance is associated with an increased risk of fracture. Higher rates of periprosthetic fractures and implant loosening were also reported. Furthermore, the patient’s general condition and associated comorbid disease must always be taken into account. Paraplegic patients have impaired microvasculature over skin and subcutaneous tissues, with long-lasting proprioception and exteroception damage. Occlusion across capillaries and small vessels followed by metabolic alteration may cause improper wound healing and further deterioration of the postoperative general state of such patients [69].
Regarding our case, the patient presented with missed injury and overlooked diagnosis, mainly due to the late presentation to healthcare facilities with inadequate treatment in the initial contact. Furthermore, the lack of adequate further follow-up, sociopsychological support, and rehabilitative care, subsequent to the discharge from the initial treatment, also played an important role in the deteriorating progression toward the worsened condition of the patient (Fig. 7). Rehabilitation with physical therapy became the preferred treatment modality for the patient. We implemented several principles of physical therapy, including passive stretching of muscles and joints, promotion of extension positioning of the limb, splinting or serial plastering/casting to manage, prevent, and delay further progression of the contracture in our patient.
We performed passive stretching with assisted continuous skin traction and serial plastering. Passive stretching 3–6 times a day with a total duration of 30–60 minutes was conducted at the beginning of the first 2 weeks, followed by continuous traction for 3 weeks. Serial plastering and bracing were changed toward the new limit of range at regular times. In the end of the fifth week, range of movement (ROM) in our patient had improved with a final ROM of hip flexion of more than 90° bilateral, 110° in right knee, and 115° in left knee. At 3 months postdischarge, hip flexion ROM was 90° bilaterally, with knee extension ROM increased to 25° bilaterally. The patient was not burdened by a bedridden condition anymore and could ambulate using a wheelchair.
Although the effectiveness and success of passive stretching are influenced by the characteristics of the contracture and predisposing factors in each patient, prolonged and sustained passive stretching over the contracture region had showed favorable outcomes compared with shortened duration. Daily stretching of 30 minutes over the immobilized joint was reported to prevent sarcomere loss. Another study showed that sustained stretching of 50 minutes was effective to counteract the dynamic changes in muscle and connective tissue [49]. Prolonged stretching with the help of other modalities may be considered when a passive movement pattern has failed to achieve the expected ROM of the contracture. Besides, the presented static postures sustained by spasticity of the neuromuscular changes must be taken into account as well [49, 68].
Application of serial plastering plays an important role in maintaining continuous immobilization. In addition, antagonist muscle of the stretched muscle may suffer changes due to the shortening and the emergence of minimal atrophy. The use of serial plastering in a lower limb flexion contracture has showed positive outcome with full extension accomplished in the best case [64, 70]. The length–tension curve may shift toward the flexion or opposite direction of the contracture as well. Cusick et al. reported the application of serial casting in a case study, showing regained full extension of the right leg with residual 5° contracture of the left leg prior to bilateral 40° flexion contracture. Increased ankle range of dorsiflexion was reported by Brouwer et al. in the 3 weeks after serial casting. Plantar-flexor strength was preserved in the study [49]. Increased range of dorsiflexion and decreased tone of plantar-flexor were also observed in a patient with cortical lesion undergoing serial casting [71]. However, recurrence may occur due to persisting spasticity. Besides, prolonged immobilization in serial plastering may cause alter the muscle/tendon ratio with a length–peak torque shift of the muscle, further resulting in muscle atrophy, muscle weakness, and decreased elasticity of the connective tissue.
Other major complications associated with the neglected case of prolonged knee–chest positioning in our patient were severe malnutrition, CAP, multiple skin lesion with pressure ulcer grade 2 and 3, and poor skin hygiene. Besides, radiographic studies also showed decreased density and porotic bone over both limbs and the body. Severe malnutrition impairs the tissue repair response to the disequilibrium state of the patient. Our patient presented toward a catabolic state with the development of body wasting. Increased nutritional demand with decreased nutritional intake was found in our patient. Severe malnutrition was also associated with impaired immune system, resulting in the patient’s being susceptible to infection in the pulmonary, genitourinary, and gastrointestinal tracts. Tissue changes in the patient resulted from thicker reduplicated basement membrane with enlarged endothelial cells. These further led to occlusion of capillaries and small vessels and disruption of skin microvasculature [69]. Skin functions as a barrier to protect against pathogens and mechanical stress, and temperature, and for peripheral circulation regulation, as well as a sensing organ, being impaired here. Pressure ulcers may increase the risk of contracture formation. However, pressure ulcers in our patient emerged due to the contracture in the bedridden condition. This pressure ulcer itself may aggravate the existing contracture through a pain and infection mechanism. In our case, we decided to perform a nonsurgical approach to the patient due to his general condition with these associated comorbidities.
