I. Type I Botulinum Toxin
Evidence
Dose-control studies for the relief of lower extremity spasticity showed significant dose-effect correlations between gait dynamics and kinematics, with more significant ankle dorsiflexion activity and longer-lasting utility in the standing position or swing at higher doses than at lower doses [2 (]1 Level I evidence). Randomized controlled studies using a gross motor function test scale assessed showed that botulinum toxin type A significantly improved lower extremity function and improved gait [3-4 (]1 Level I evidence, 1 Level II evidence). In the case-control study, 12 weeks after treatment with botulinum toxin type A, the gait of the children was analyzed by applying the Physician’s Evaluation Scale, which showed a significant improvement in gait, with scores two times higher than those of normal controls [3 (]1 Level I evidence). A controlled study using botulinum toxin type A versus placebo demonstrated a significant improvement in lower extremity function in the treatment group compared to the placebo group [5-7 (]3 Level I evidence).
Relief of upper extremity spasticity
Studies have shown that botulinum toxin type A injections significantly improve upper extremity function in the short term, but not in the long term [8-11 (]4 Class I evidence). Combined OT was more effective, enhancing active elbow and thumb extension, as well as reducing muscle tone at the wrist and elbow, but functional tests of hand grasp were only slightly improved, and coin pick-up tests showed no significant improvement in hand function [12 (]1 Level II evidence). A randomized controlled trial looking at the results of repeated upper extremity injections of botulinum toxin type A combined with OT versus OT treatment alone found that the method resulted in sustained relief of spasticity and that parents could perceive significant improvement in the child [9 (]1 Level I evidence). Retrospective studies have shown low serious adverse events with botulinum toxin type A injections [13 (]1 Level I evidence).
Recommendations
Botulinum toxin type A injections are an effective and safe treatment technique for the relief of spasticity and are more effective in relieving lower extremity spasticity than in relieving upper extremity spasticity (strength of recommendation grade A).
II. Phenol, ethanol
Evidence
Local injections of ethanol and phenol can be used to relieve localized spasticity in children with cerebral palsy [14-16 (]3 Level IV evidence). no reports in the literature after 1971, but the application of ethanol, phenol, and botulinum toxin type A by experts for the treatment of spasticity by local injection, respectively, was still reported at the International Society for Physical Medicine and Rehabilitation in 2014.
Recommendations
It can be used in conjunction with botulinum toxin type A for the relief of localized spasticity in children with cerebral palsy (recommended strength D).
Diazepam
Evidence
A large sample of randomized controlled studies showed a dose-dependent reduction in muscle tone, increased passive range of motion, and improved voluntary motor ability after 3 weeks of diazepam treatment, but no significant functional improvement [17 (]1 Level I evidence). Diazepam in combination with dantrolene provided significant relief of spasticity compared with the placebo group [18 (]1 Level II evidence). Diazepam has also been reported to improve behavior and coordination in children with cerebral palsy [19 (]1 Level II evidence).
Recommendations
Short-term application of diazepam relieves generalized spasticity in children with cerebral palsy (recommended strength A) and is effective in combination with dantrolene (recommended strength B).
IV. Dantrolene
Evidence
Dantrolene improves tendon reflexes and reduces scissor step [20 (]1 level II evidence). No significant effects of dantrolene on spasticity, locomotion and muscle strength have been reported [21 (]1 Level I evidence); however, another study at the same dose (4-12 mg/kg?d) showed that dantrolene reduced spasticity, and although there was no improvement in gross motor function, activities of daily living (including coordination in dressing and eating, limb control during voluntary play endurance and freedom of movement) was significantly improved [22 (]1 Level II evidence).
Recommendations
Dantrolene improves tendon reflexes, scissor gait, and activities of daily living (level B strength of recommendation).
Dantrolene relieves spasticity in cerebral palsy, but it is controversial (recommended strength grade B).
V. Baclofen
Evidence
The results of studies of oral baclofen are less consistent, with the results of a double-blind crossover trial using doses of 10-60 mg daily showing that baclofen reduces spasticity, as evidenced by increased passive joint mobility, but no significant functional improvement in children who can walk independently [23 (]1 Level II evidence); another double-blind placebo crossover trial, using the same dose and age grouping and assessed with the Aim Reach Scale found improved outcomes, but the application of the modified Tardieu Scale and the Pediatric Evaluation of Disabilityinventory (PEDI), which assesses children, found no significant improvement in spasticity or function [24 (]1 Level II evidence). Intrathecal baclofen provided long-term relief of spasticity and improved motor function in children with cerebral palsy [25-30 (]1 level III evidence, 5 level IV evidence). Side effects of intrathecal baclofen include cerebrospinal fluid leakage, catheter failure, and soft tissue infection [31 (]1 Level II evidence).
Recommendations
Oral baclofen relieves spasticity and increased passive joint mobility in children with cerebral palsy and remains somewhat controversial (strength of recommendation B).
Intrathecal baclofen may relieve spasticity and improve motor function in children with cerebral palsy, with the need to prevent side effects (Grade C strength of recommendation).
VI. Tizanidine
Evidence
A small sample of placebo-controlled studies using tizanidine at a dose of 0.05 mg/kg?d for 2 weeks found reduced spasticity, improved posture and tendon reflexes, but no functional assessment was done and no side effects were observed, and liver function was normal, and the drug was considered to have potential for the treatment of spasticity relief in children with cerebral palsy [32 (]1 Level II evidence).
Recommendations
Tizanidine may reduce spasticity (strength of recommendation B).
VII. Levetiracetam
Evidence
Studies showing the application of levetiracetam monotherapy in 2 children with involuntary motor cerebral palsy have shown impressive improvement in balance control and fine motor using video and visual analog scales to assess outcomes, no side effects were found, and the treatment effect was maintained for more than 26 months [33 (]1 month or more [33 (]1 level IV evidence).
Recommendations
Levetiracetam improves balance control and fine motor movements in children with involuntary motor cerebral palsy (level D strength of recommendation).
VIII. Bisphosphonates, vitamin D, and calcium supplements
Evidence
Randomized, placebo-controlled clinical trials suggest that disodium aminodiphosphate improves bone mineral density in children with cerebral palsy, is a safe and very effective approach [34 (]1 Level I evidence), and reduces the risk of fracture [35 (]1 Level II evidence). Oral sodium allantoinate 1 mg/kg/week can treat osteoporosis in children with cerebral palsy in combination with positive efficacy [36 (]1 Level II evidence). Children taking concomitant antiepileptic drugs need to consume higher than normal recommended intake of vitamin D and calcium supplements to maintain bone mineral density [37 (]1 Level III evidence).
Recommendations
Disodium alemphate may improve bone mineral density in children with cerebral palsy (Grade A strength of recommendation).
Oral sodium allantoinate may treat combined osteoporosis in children with cerebral palsy (level B strength of recommendation).
Children with cerebral palsy taking antiepileptic drugs need to consume higher than normal recommended intake of vitamin D and calcium supplements (level C).
IX. Nerve growth factor
Evidence
Nerve growth factor has the ability to promote neuronal survival, axon directed regeneration, myelin production and promote effective connectivity to restore sensory, motor and cognitive functions. Murine nerve growth factor has been reported to be effective in stroke, craniocerebral injury, spinal cord injury, peripheral neuropathy and peripheral nerve injury, and neonatal hypoxic-ischemic encephalopathy [38-40 (]3 Level II evidence). Nerve growth factor has been studied to improve motor and mental development, as well as improve muscle tone, postural abnormalities, and reflex abnormalities in infantile cerebral palsy [41-44 (] 4 Level IV evidence). However, there is a lack of evidence-based medical rationale for controlled studies in large cohorts.
Recommendations
Nerve growth factor can be used in the treatment of hypoxic-ischemic encephalopathy, spinal cord and peripheral nerve injury, etc. The application in the treatment of cerebral palsy lacks evidence-based medical evidence from large sample studies (strength of recommendation D).
Section V. Surgical treatment
I. Orthopedic surgery
Evidence
There are various orthopedic surgical methods for cerebral palsy. Tendon lengthening, tendon transfer, and rotational osteotomy are commonly used orthopedic surgical methods for progressive cerebral palsy musculoskeletal lesions. Choosing the right time for orthopedic surgery can relieve muscle spasm, balance muscle strength, correct deformity, adjust the negative gravity line of the limb, improve motor function, and create favorable conditions for rehabilitation treatment.
Upper limb orthopedic surgery for cerebral palsy is complex and challenging, and its purpose is to restore the ability of daily living activities, motor function, and improve the appearance of the hand. Orthopedic surgery of the upper limb in cerebral palsy includes: thumb inversion deformity surgery, ulnar nerve motor branch severance, interosseous muscle, pinky flexor muscle, metacarpal interosseous muscle severance, wrist joint fusion, ulnar carpal flexor transfer, rotary anterior circular muscle release, etc. The efficacy of all upper extremity orthopedic surgery lacks valid evidence to support [1-3 (]3 level IV evidence).
Spinal orthopedic surgery for scoliosis in cerebral palsy is more complex, and there is some difficulty in determining whether to operate and which procedure to adopt. When a patient has a scoliosis Cobb angle of 40° or more, surgical treatment can be considered, mostly with spinal fusion. Spinal fusion is feasible in cerebral palsy with neurological scoliosis [4-7 (]2 level III evidence, 2 level IV evidence) to correct the spinal deformity and correct the pelvic tilt, and the application of cervical/brainstem somatosensory evoked potentials for spinal cord monitoring is recommended at the time of surgery to avoid serious complications. Spinal fusion may cause digestive dysfunction and heterotopic ossification after surgery, and simultaneous hip and spine surgery should be avoided.
Lower limb orthopedic surgery: abnormal gait often occurs during the development of cerebral palsy, and the bones and joints of the lower limbs may produce various contracture deformities. The main principle of lower limb orthopedic surgery is to correct the force line and balance the muscle strength.
(1) Joint orthopedic surgery: hip dislocation is more common in spastic cerebral palsy, but there is still no uniformity in the timing and prognosis of surgery. Comprehensive surgery is effective in treating spastic hip dislocation. The surgical method is femoral rotational osteotomy + hip osteotomy/pelvic osteotomy, and pelvic osteotomy is suitable for children aged 1-6 years old, with acetabular index less than 45° and the size of femoral head basically adapted to the acetabulum. Soft tissue release surgery combined with femoral rotation osteotomy can correct pelvic rotation in cerebral palsy, acetabuloplasty combined with femoral osteotomy and soft tissue release can improve femoral head deformity in children with cerebral palsy, and lumbaris major and associated soft tissue release surgery combined with proximal femoral shortening and Chiari osteotomy is effective in adolescents or adults with cerebral palsy who are subluxed and have pain [8-15(] (2 Level III evidence, 6 Level IV evidence). Total hip arthroplasty is feasible in cerebral palsy with severe hip disorders, and proximal femoral resection arthroplasty may be effective in patients with spastic cerebral palsy with hip pain and dislocation. Unilateral hip surgery is relatively contraindicated in patients with severe spastic biplegia or quadriplegia, and is not indicated in patients under 6 years of age or in those with mild hip dislocation. Soft tissue surgery in children with spastic cerebral palsy, including psoas major muscle dissection, psoas-rectus femoris transfer, simple adductor muscle dissection, and adductor muscle dissection combined with closed-hole neurectomy, can reduce the incidence of hip dislocation and prevent spastic hip dislocation [16-18 (]1 level II evidence, 1 level III evidence, and 1 level IV evidence). Soft tissue release is not recommended for cerebral palsy with hip instability. Conventional soft tissue surgery, although it does not reduce hypertonia, may correct fixed contractures and deformities. For hip flexion deformity, lumbar muscle release and rectus femoris muscle release are often used. For hip adduction deformity, the adductor muscle is often cut or combined with the anterior branch of the closed foramen nerve cut. Soft tissue release surgery can improve the gait of children with cerebral palsy; internal short muscle and thin femoral muscle transfer can correct scissor gait, and rectus femoris muscle transfer and N cord muscle surgery can increase gait length [19-21 (]1 level III evidence, 2 level IV evidence).
(2) Knee orthopedic surgery: rectus femoris transfer and N cord surgery can be used to treat spastic cerebral palsy with mobility by increasing the knee extension angle and increasing stride length in the standing position of the child. Rectus femoris transfer is feasible in cerebral palsy with a rigid gait [22-23 (]2 Level III evidence). When the range of motion of the knee in cerebral palsy is less than 80% of normal, rectus femoris transfer should be performed and distal rectus femoris release should not be performed. Proximal rectus femoris release does not improve hip flexor contracture and gait abnormalities in spastic cerebral palsy. distal rectus femoris transfer in GMFCS grade IV cerebral palsy increases postoperative knee flexion, and distal rectus femoris transfer in GMFCS grade IV cerebral palsy is contraindicated. Medial and lateral lengthening of the N cord muscle in spastic cerebral palsy improves the N fossa angle, increases the maximum knee extension angle in the upright position, and improves walking ability and motor function, but the risk of knee hyperextension is higher than that of medial lengthening of the N cord muscle [24-27] (2 Level III evidence, 2 Level IV evidence). Soft tissue orthopedic plus Ilizarov external fixation brace for spastic cerebral palsy with severe flexion knee deformity can achieve more satisfactory results.
(3) Ankle orthopedic surgery: Achilles tendon lengthening is feasible for spastic cerebral palsy with horseshoe foot to correct the deformity and improve spasticity [28-32 (]1 grade II evidence, 2 grade III evidence, 2 grade IV evidence). Cerebral palsy Achilles tendon lengthening is effective, but triceps strength is reduced and requires the use of a ground reaction brace. Achilles tendon lengthening is most effective in hemiplegia, non-hemiplegic cerebral palsy requiring unilateral surgery, and cerebral palsy not requiring late surgical procedures. For cerebral palsy with fixed and dynamic clubfoot, gastrocnemius fascia lengthening, gastrocnemius-fibularis lengthening, and triceps calf lengthening are required. Partial transfer of the posterior tibial muscle and tendon lengthening are feasible in children with hemiplegic cerebral palsy with spastic clubfoot deformity. Posterior tibial muscle surgery should not be performed in biplegic and quadriplegic cerebral palsy under 8 years of age or in those who cannot walk independently in the community. In cerebral palsy clubfoot, conservative treatment and soft tissue surgery are generally considered until the age of 6 years, and bony surgery should be used to correct clubfoot in older children. Extra-articular subtalar joint fusion can correct posterior foot valgus in cerebral palsy [33-38 (]3 level III evidence, 3 level IV evidence), improve spastic flatfoot deformity in cerebral palsy, and correct midfoot valgus, but it cannot correct foot valgus deformity combined with severe forefoot abduction deformity and cannot correct forefoot rotation back and heel plantar flexion. Modified subtalar joint fusion is effective for dorsal talocalcaneal subluxation in children with cerebral palsy.
(4) Single-eventmultilevelsurgery (SEMS) under one anesthetic: SEMS, also known as multi-site surgery or gait improvement surgery, refers to the correction of soft tissue and bony deformities in multiple sites under one anesthetic. SEMS is recommended for spastic cerebral palsy with mobility to improve static contractures and knee motor function, improve motor function, gait, mobility, gross motor function, and quality of life in children with high postoperative patient parental satisfaction [39-48 (]5 Level II evidence, 2 Level III evidence, and 3 Level IV evidence). The long-term outcome of SEMS in older children with cerebral palsy is good. SEMS for spastic biplegia with severe gait abnormalities only improves the gait of the child in the short term, and many patients require other surgical treatments. Children with cerebral palsy who underwent SEMS of the upper extremities did not have significantly improved grip-extension ability compared with children without surgery [49 (]1 Level III evidence).
Recommendations
Spinal fusion is the treatment for neuromuscular scoliosis cerebral palsy (strength of recommendation grade C).
Comprehensive surgical options (soft tissue surgery combined with femoral rotational osteotomy, femoral inversion rotational osteotomy combined with hip resurfacing/pelvic osteotomy) are an option for the treatment of patients with spastic hip dislocation cerebral palsy (grade C strength of recommendation).
Soft tissue surgery is a treatment option to prevent hip dislocation in spastic cerebral palsy (recommended intensity level C).
Soft tissue surgery is a treatment option to correct fixed contractures and deformities of the lower extremities and improve abnormal gait (recommended intensity level C).
Rectus femoris transfer is a treatment option for rigid gait cerebral palsy (recommended intensity level C).
Cord lengthening is a treatment option to improve knee mobility in spastic cerebral palsy (recommended intensity level C).
Achilles tendon lengthening is a treatment option for spastic horseshoe foot deformity cerebral palsy (recommended intensity level C).
Extra-articular subtalar joint fusion is a treatment option for cerebral palsy with clubfoot deformity (recommended intensity level C).
Spastic cerebral palsy with mobility is an option to improve gait (recommended intensity B).
II. Posterior spinal nerve rhizotomy
Evidence
Selective posterior rhizotomy (SPR/selectivedorsalrhizotomy, SDR) requires selection of L2-L5 and S1 posterior root segments according to the specific situation of the child and the site of spasticity, together with electrical stimulation monitoring and personal experience to selectively Cutting the cauda equina is an important factor in determining the outcome, and selecting the right patient is crucial to the success of the procedure. Posterior spinal nerve rhizotomy is effective in reducing spasticity, improving function, and enhancing walking ability in moderate to severe spastic cerebral palsy, with positive long-term effects on the physical agency and functional domains of cerebral palsy [50-57 (]2 Level I evidence, 5 Level III evidence, and 1 Level IV evidence). Posterior spinal nerve rhizotomy may be most effective for cerebral palsy in children 3-8 years of age, GMFCS grades III-IV [58 (]1 level I evidence), but has a weak long-term improvement in children with GMFCS grades II-III and no long-term sustained improvement in children with GMFCS grades IV-V [59 (]1 level III evidence). Posterior spinal nerve rhizotomy is feasible for spastic biplegia, mild tetraplegia, cerebral palsy in which intrathecal baclofen cannot be administered or is unresponsive to medication, and is contraindicated in children with spastic quadriplegia requiring wheelchair mobility and mental retardation, cerebral palsy over 10 years of age, dystonia, tardive dyskinesia, and ataxia. Selective posterior cervical nerve rhizotomy can relieve upper limb spasticity and improve limb function, but some patients still have deformities such as elbow flexion, forearm rotation and wrist flexion after surgery. Intraoperative electrophysiologic monitoring should be performed during posterior rhizotomy of the spinal nerve. Posterior rhizotomy has an impact on the stability of the lumbar spine in children with cerebral palsy, and postoperative spinal deformities such as lumbar hyperlordosis, vertebral detachment, and spinal slippage can occur, with complications such as bronchospasm, pneumonia, urinary retention, and sensory loss [60-61 (]2 Level III evidence).
Recommendations
Posterior spinal nerve rhizotomy is an option for the treatment of spastic cerebral palsy in 3-8-year-old, GMFCS grade III-IV lower limbs, but the indications should be strictly controlled (grade A strength of recommendation).
III. Baclofen intrathecal injection
Evidence
Intrathecal baclofentherapy (IBT) is effective in intractable spastic cerebral palsy, providing antispasticity, improved speech, communication, and salivation control, reduced bowel movements, positive effects on pain and motor deficits, improved gait, improved comfort in wheelchairs for children with cerebral palsy who have difficulty with conventional antispastic therapy, and improved ease of care. Intrathecal baclofen is safe and effective in the treatment of patients with severe spasticity, patients refractory to conventional oral therapy, and patients with mixed cerebral palsy [62-67 (]3 Level II evidence, 3 Level IV evidence). The incidence of complications from intrathecal baclofen treatment was 44%, the rate of secondary infection was 73%, and the rate of complications and surgical treatment was 31%.
Recommendations
Intrathecal baclofen is an option for the treatment of children with severe spastic cerebral palsy (strength of recommendation grade C).
IV. Minimally invasive peripheral nerve surgery
Evidence
Selective peripheral neurotomy (tibial nerve, sciatic nerve, musculocutaneous nerve, median nerve, ulnar nerve, paramedian nerve, anterior and posterior roots of spinal nerves in the cervical and lumbosacral segments) is a safe and effective surgical procedure for the treatment of spastic cerebral palsy, reducing muscle tone, correcting spastic deformities, and improving motor function [68-69 (]2 level IV evidence). Selective peripheral neurotomy can relieve spasticity and improve function in spastic cerebral palsy where conservative treatment has failed [70-73 (]4 Level IV evidence). Selective tibial nerve branchotomy for spastic clubfoot in cerebral palsy reduces muscle tone. Selective femoral nerve dissection improves knee stiffness and increases knee mobility due to quadriceps spasm. Peripheral nerve selective neurotomy for lower limb spasticity, with some patients experiencing decreased muscle strength and limb numbness. The efficacy of minimally invasive peripheral nerve procedures such as selective neurotomy of the external shoulder rotators, C7 nerve rhizotomy, C8 nerve rhizotomy, and percutaneous radiofrequency disruption of the dorsal root ganglion lacks valid evidence to support [74 (]1 level IV evidence). Selective neurotomy of the external shoulder rotators relieves muscle spasticity in children with cerebral palsy; C7 nerve root dissection and contralateral healthy C7 nerve root transfer to the middle trunk of the affected brachial plexus partially relieves flexor spasticity and enhances extensor strength in cerebral palsy; C8 nerve root dissection does not provide long-term relief of hand spasticity in cerebral palsy, and spasticity treatment is poor [75 (]1 Level IV evidence). Dorsal ganglion percutaneous radiofrequency disruption surgery for cerebral palsy with severe painful hip flexion/inflexion spasticity improves spasticity, pain, and makes care easier [76 (]1 Level IV evidence).
Recommendations
Selective partial peripheral nerve dissection is a treatment option for spastic cerebral palsy that has failed to respond to conservative treatment (strength of recommendation grade D).