Cerebral palsy

Abstract

Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging.

Figure 1 |. Gross Motor Function Classification System expanded and revised for children with cerebral palsy, 6–12 years of age.

The Gross Motor Function Classification System (GMFCS) has become the gold standard to classify motor function in children with cerebral palsy. The GMFCS is an ordinal classification in which different descriptors are used according to the age of the child. The descriptors for children 6–12 years of age are shown. GMFCS has been shown to be valid, reliable, stable and predictive of long-term gross motor function. The descriptors were devised by Palisano et al.^,. Images are courtesy of B. Reid, A. Harvey and H.K.G., The Royal Children’s Hospital, Melbourne, Victoria, Australia.

Figure 2 |. Topographical description in cerebral palsy: unilateral and bilateral cerebral palsy.

In monoplegia, one limb is affected and it is more often the lower limb. In hemiplegia, one side of the body is affected and the upper limb is usually more affected than the lower limb. These topographical types are equivalent to the Surveillance of Cerebral Palsy Europe (SCPE) unilateral cerebral palsy. In diplegia, all limbs are affected, but the lower limbs are much more affected than the upper limbs, which frequently only show fine motor impairment. In triplegia, the usual pattern is unilateral upper limb involvement and bilateral (asymmetrical) lower limb involvement. The lower limb is invariably more affected on the same side as the upper limb involvement. In quadriplegia, all four limbs and the trunk are involved. Synonyms for quadriplegia include tetraplegia or ‘whole-body involvement’. Diplegia, triplegia and quadriplegia are covered by the term bilateral cerebral palsy according to SCPE terminology.

Figure 3 |. Association between gestational age and the prevalence of cerebral palsy.

The ‘paradox’ is the very strong relationship between prematurity and risk of cerebral palsy versus the fact that most patients with cerebral palsy are born at term. Graph is based on data described in REF. .

Figure 4 |. Brain lesions in cerebral palsy.

a | Coronal (left) and axial (right) MRI scans at 32 weeks of gestation showing frontal lobe hypoplasia and polymicrogyria (arrow). The child developed severe bilateral spastic cerebral palsy (Gross Motor Function Classification System (GMFCS) level V). b | Axial (left) and sagittal (right) MRI (spin echo T2 and spin echo T1) scans obtained at 5 weeks in an infant born preterm (at 30 weeks of gestation). Images show cystic periventricular leukomalacia (arrow). The child developed severe bilateral spastic cerebral palsy (GMFCS level IV). c | Axial MRI (inversion recovery) images obtained at 3 years in a child with birth asphyxia at term, showing cortico–subcortical atrophy particularly marked in the perirolandic region (asterisk) and porencephalic cysts in the basal ganglia bilaterally (arrow). The child had severe mixed-type (spastic and dyskinetic) cerebral palsy (GMFCS level V). Images are courtesy of C. Christophe, Université Libre de Bruxelles, Brussels, Belgium, and M. Cassart, Ixelles Hospital, Brussels, Belgium.

Figure 5 |. Cell death signalling pathways.

Extrinsic and intrinsic cell death pathways activate common signalling networks within the mitochondrion and the nucleus. The extrinsic pathway is triggered by inflammatory cytokines binding to the cell surface to activate FAS (also known as TNFRSF6 or CD95) death receptors and N-methyl-D-aspartate (NMDA) receptor-activated excitotoxic action of glutamate. The intrinsic pathway is activated when signals released from within stressed mitochondria activate caspase-mediated and non-caspase-mediated cell death pathways within the nucleus. Mitochondria that are exposed to caspase-induced stress can release cytochrome c (caspase-mediated cell death) or apoptosis-inducing factor, which activates DNA fragmentation directly (non-caspase pathway). DNA breaks can be mediated by free radicals, such as nitric oxide (NO). V_m, membrane potential; VSCC, voltage-sensitive Ca²⁺ channel.

Figure 6 |. Structural changes observed in muscle of children with cerebral palsy compared with typically developing children.

a,b | Schematic representation of the long sarcomere lengths observed in children with cerebral palsy (part b) compared with the shorter sarcomere lengths observed in typically developing children (part a). This dramatic sarcomere length difference is observed even though the overall fascicle lengths of the two muscles are nearly identical. c,d | Schematic representation of the growth in muscle from typically developing children as bone length increases. Sarcomeres are added in series as the bone grows, and therefore the ankle retains full range of motion (part c, right image). However, in a child with cerebral palsy, we hypothesize that sarcomeres are not added in series and thus, as the bone grows, the ankle is forced into plantar flexion (part d, right image). In the panels on the left, the microscopic appearance of muscle is shown. In cross-sections, muscle fibres from typically developing children are larger compared with fibres of children with cerebral palsy. In addition, in longitudinal sections, fibres from typically developing children have more satellite cells compared with children with cerebral palsy. e–h | Immunohistochemical staining of human muscle for laminin, one of the constituents of the extracellular matrix (ECM). Part e and part g are cross-sections, whereas part f and part h are longitudinal sections. Note the increased amount of ECM in muscle from children with cerebral palsy (part g and part h). Part c and part d adapted with permission from REF. , Wiley. Parts e–h reproduced with permission from REF. , Wiley.

Figure 7 |. Movement disorders in cerebral palsy.

Central nervous system (CNS) lesions and/or reorganization can lead to movement disorders, which can be electromyographically (EMG) active or lead to EMG-silent trophic muscle changes and contracture. When the movement disorders are independent of sleep, loss of supraspinal (central) neuronal inhibition should be suspected, leading to a spastic response characterized by a disorder of velocity-dependent stretch reflexes. Dystonic disorders are inhibited by sleep and either present as a movement disorder (abnormal proximal-to-distal muscle sequencing with co-contraction) and/or a postural disorder (abnormal tonic labyrinthine reflexes, with scissoring or fisting). In dystonia, sustained EMG discharges are present ‘at rest’ and are length dependent (worsened by slow stretch) and arousal dependent. The majority of management strategies that have emerged over the past 70 years are depicted in the orange boxes. Management depends on the patient characteristics. All management plans aim to support innate adaptive motor development, but the anatomy and physiology of the muscles in cerebral palsy inexorably tends towards fixed, irreversible deformity and muscle contracture over time. Management strategies include seating systems, communication aids, neurosurgical interventions (deep brain stimulation (DBS), intrathecal baclofen (ITB) and selective dorsal rhizotomy (SDR)), pharmacological approaches and orthopaedic surgery: all within a multidisciplinary team and according to the WHO International Classification of Function Children and Youth version 2007 (WHO-ICF-C-Y 2007). BoNT-A, botulinum neurotoxin A.

Figure 8 |. Stance phase and sagittal ankle kinematics: typically developing gait.

a | Stance phase can be divided into sub-phases that may include: initial contact, loading response, mid-stance, terminal stance and pre-swing. In each of the phases, the direction of the ground reaction force is indicated by the red arrow. b | The angle of the ankle is indicated, with the solid blue line indicating mean ankle dorsiflexion for typically developing gait and the dashed blue lines indicating two standard deviations around the mean.

Figure 9 |. Upper motor neuron syndrome.

In cerebral palsy, the injury to the upper motor neurons (UMNs) results in two kinds of effects. The predominant and most important effect results from loss of corticospinal tract connections to lower motor neurons (LMNs) and hence to skeletal muscles. This causes paresis or partial paralysis, which is usually more pronounced for distal muscles than proximal muscles. By contrast, hypertonia is hypothesized to be caused by the loss of inhibitory descending input to the LMNs, which keeps the stretch reflex in the peripheral neuromuscular system from being overactive. This results in hypertonia and hyper-reflexia. The effects of the brain lesion in children with cerebral palsy may extend to all parts of the musculoskeletal system, particularly in children with more-severe motor impairment. Some of the typical postures and deformities in the upper limbs, the spine and pelvis, the hips and the lower limbs (contractures and long bone torsion) are shown. In general, the effects of the UMN syndrome can be considered as a group of ‘positive’ features (for example, too much tone) and as a group of ‘negative’ features (including too little selective motor control and strength). Traditionally, the positive features and their amelioration by intervention strategies have been overemphasized. By contrast, the negative features have received much less attention until recently. For example, hip displacement has largely been attributed to adductor spasticity and contracture, but management based on alleviating these features has little effect. Recent studies that report a linear relationship between the prevalence of hip displacement and Gross Motor Function Classification System level strongly suggest that it is the negative features that are more important. CNS, central nervous system.

Figure 10 |. The role of ankle foot orthoses in ambulant children with cerebral palsy.

a,b | Ankle foot orthoses (AFOs) may be prescribed to improve gait and function for both swing-phase and stance-phase problems during gait. Part a and part b are based on sagittal plane videos of an 8-year-old boy with right spastic hemiplegia who attended the Hugh Williamson Gait Laboratory, The Royal Children’s Hospital, Melbourne, Victoria, Australia. The right leg is in late swing and shows equinus (dashed blue line), which was the result of spasticity in the gastrocsoleus muscle combined with poor selective motor control. This leads to tripping and falling (part a). The AFO corrects the equinus, resulting in a normal heel strike and a more normal sequence of ankle rockers (part b). c,d | In older children and many adolescents with cerebral palsy, excessive knee flexion and crouch gait are common. In these figures derived from sagittal plane videos of a 12-year-old boy with spastic diplegia and crouch gait, neither the knees nor the hips extend fully in late stance. The red arrow indicates the direction of the ground reaction force, which is posterior to the knee. This results in an excessive demand on the quadriceps to prevent further sinking and falling. The ankle is also excessively dorsiflexed (part c). When bilateral floor reaction AFOs are worn, the ground reaction force is redirected in front of the knee, excessive ankle dorsiflexion is blocked and both the knee and the hip show improved extension, reducing the demand on the quadriceps and resulting in a more erect, energy-efficient gait pattern (part d).

Figure 11 |. Quality-of-life scores by domain of the KIDSCREEN questionnaire.

Quality-of-live (QOL) domains affected by cerebral palsy in children and adolescents. Data collated from reports in REFS ,.