# data[].attributes.attachment_link.readable_text
It is our belief that knowledge is power. The easier information is to obtain and understand, the more your child benefits. Information is the vital tool that equips us all with an ability to make clear, informed decisions on health, education, wellness, and more. It's almost always true that the more information, the better the potential outcome.

MyChild™ provides information on topics from A to Z, all made available here, for your convenience. After decades representing families of special needs children, and protecting their rights in the courts and in state legislative hearings, attorney Ken Stern recognized the need for an informative resource where all parents could quickly access needed information to learn, understand and to protect their child. My Child TM, including the website CerebralPalsy.org, its Facebook page, and the MyChild TM Call Center are owned by Ken Stern and serve to make information and compassionate understanding readily available to those who need it most - parents just like you.

Beyond an informational resource, our website features stories of success and inspiration regarding children and adults living with Cerebral Palsy, embracing their challenges and achieving amazing things we hope inspire you as much as they do us. Contact us today for free information on anything related to Cerebral Palsy - we're here to help your child achieve their full potential in any way that we can. For the information you need, and that your child deserves, we're here for you!

# data[].attributes.attachment_link.title
CerebralPalsy.org | Help, Resources for Children with CP

# data[].attributes.attachment_link.description
CerebralPalsy.org is your ultimate resource for everything Cerebral Palsy. Contact us today for assistance and help for your child living with CP!

# data[].attributes.body
“Cerebral Palsy Treatment - What Treatment Works Best?” Cerebral Palsy Guide, 2019, www.cerebralpalsyguide.com/treatment/.

“What Is Cerebral Palsy?” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 11 Sept. 2020, www.cdc.gov/ncbddd/cp/facts.html.

“Cerebral Palsy.” ASHA Cerebral Palsy, American Speech-Language-Hearing Association, 2017, www.asha.org/Events/convention/handouts/2013/1032-Ward/.

# data[].attributes.body
ensure patients are getting the support and treatment they need and that family members/friends are caring for them.

# data[].attributes.body
Physical therapy

One of the first steps for treating CP

strength and flexibility exercises

heat treatment

massages and special equipment

can improve things like coordination, strength, balance

Occupational therapy

helps develop and recover skills that are needed

playing and learning are activities OT works on developing

helps with muscle and joint coordination

improves physical, cognitive, and social abilities and fine motor skills

Speech therapy

improves overall understanding of language

strengthen muscles for speech

improve a patients understanding of speech and language

improve swallowing disorders

Pharmacology

no medicine to cure CP

medication can be used for symptom release

common medicines used:

antidepressants

muscle relaxants

nerve blocks

botox

stool softeners

Surgery

can improve alignment and movements

usually suggested after exhausting other options

can help with posture, decrease tremors, relieve stiff muscles and pain

# data[].attributes.attachment_link.title
Cerebral Palsy Treatment - What Are The Treatment Options?

# data[].attributes.attachment_link.description
Cerebral palsy treatment can vary based on your child’s specific symptoms. Treatment can include therapy, medication, surgery, and more.

# data[].attributes.attachment_link.title
Treatments for Cerebral Palsy (Overview)

# data[].attributes.body
These symptoms manifest as spastic, athetoid, and ataxic cerebral palsy. This type of cerebral palsy affects about 10% of people with CP.

How does mixed cerebral palsy affect you?

tremors

seizures

visual or hearing impairment

challenges performing fine motor skills

muscles tone that appears stiffer or looser than normal

skeletal abnormalitites

How does mixed cerebral palsy affect speech?

slow, monotone speecj

unusual pauses

hoarse or tight voice

difficulty swallowing

# data[].attributes.attachment_link.readable_text
Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA

Motion and Gait Analysis Lab, Lucile Packard Children's Hospital, Palo Alto, CA, USA

Thayer School of Engineering, Dartmouth College, Hanover, NH, USA

Neukom Institute for Computational Sciences, Dartmouth College, Hanover, NH, USA

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP.

Introduction

Brain Injury in Cerebral Palsy

Cerebral palsy describes "a group of permanent disorders affecting the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain" ( Rosenbaum et al., 2007). Although the initial brain injury is non-progressive, the musculoskeletal impairments and functional limitations associated with CP are indeed progressive ( Bell et al., 2002; Sanger, 2015). A loss of oxygen to the developing brain, i.e., hypoxia-ischemia, is the primary mechanism by which brain injury occurs in CP. Other causes of brain injury include hemorrhage, infection, metabolic derangement, brain malformation, and bilirubin neurotoxicity. In contrast, birth asphyxia resulting in CP is relatively rare, accounting for <10% cases, ( Paneth et al., 2006; Strijbis et al., 2006; Ellenberg and Nelson, 2013), and evidence of genetic influences on development of CP is newly emerging and thought to contribute to up to 30% of CP cases ( Costeff, 2004; Moreno-De-Luca et al., 2012; MacLennan et al., 2015). The prevalence of CP increases with prematurity, ranging from 1.1 per 1000 infants born at 40 weeks' gestation to 90.7 per 1000 infants born at 26 weeks' gestation ( Trønnes et al., 2014). The risk of CP decreases linearly with increasing gestational age: 8.5% for 23-27 weeks, 5.6% for 28-30 weeks, 2.0% for 31-33 weeks, 0.4% for 34-36 weeks, and 0.2% for 37+ weeks gestation. Male sex is also a general risk factor, as the rate of CP per 1000 male births exceeds that among females by about 30% ( Jarvis et al., 2005).

Spastic CP is often linked to damage to the periventricular WM due to hypoxia-ischemia, which may be caused by various maternal or prenatal factors. Spastic CP is further delineated by the distribution of affected limbs: hemiplegia, diplegia, and tetraplegia (also referred to as quadriplegia). Individuals with spastic CP present with varying degrees of weakness, short muscle-tendon unit, spasticity, and impaired SMC. In spastic CP, the severity of motor deficits, the distribution of affected limbs, and the extent to which the motor deficits involve distal to more proximal joints within a limb, are thought to be determined by the severity and extent of the brain injury ( Serdaroglu et al., 2004), consistent with anatomical representation of the cortical homunculus and descending fibers (Figure 1). More medial brain injury, i.e., closer to the ventricles, results in more mild involvement of distal joints. More extensive injury that extends to lateral portion of periventricular WM results in more severe involvement of both distal and proximal joints. Accordingly, Staudt et al. (2000) found a strong correlation between the extent of the lateral lesion in the posterior semi-coronal plane on MRI and the lower limb motor impairment score ( r = 0.805, p = 0.001). In addition, upper limb involvement is generally associated with a greater degree of lateral damage compared to lower limb involvement. Staudt et al. (2003) found that upper limb dysfunction was observed only in patients with a lateral lesion extent of 23 mm or more, whereas lower limb dysfunction was present with a lateral lesion extent of 20 mm.

Dyskinetic CP is the second most common type of CP, affecting approximately 7.5% of children with CP ( Sellier et al., 2016). It is often linked to damage of the subcortical GM, i.e., basal ganglia and thalamus, due to hypoxia-ischemia, as well as hyperbilirubinemia and birth asphyxia ( Himmelmann and Uvebrant, 2011). The definition of dyskinetic CP has evolved recently to include dystonic and choreoathetoid CP ( Aravamuthan and Waugh, 2016). As noted by Sanger (2006), symptoms of dyskinetic CP include both hyperkinetic and dystonic limb movements that impair function. Currently, it has not been determined whether these movements are random and variable or involve a small number of specific abnormal motor patterns ( Sanger, 2006). The severity of motor impairment in dyskinetic CP has been found to be associated with lower volumes of the basal ganglia and thalamus ( Laporta-Hoyos et al., 2014). In a study of 18 children with basal ganglia lesions and CP, 13 children had a diagnosis of dyskinetic CP, 12 had a diagnosis of dyskinetic CP with severe fine motor impairment and a GMFCS ( Palisano et al., 2008) level of IV or V, representing severe CP with reduced or absent independent mobility ( Himmelmann and Uvebrant, 2011).

Although early brain injury is the primary cause of CP, a recent study using exome sequencing reported that 14% of CP cases had causative single-gene mutations and up to 31% had clinically relevant copy number variations, suggesting a greater role of genetics in the development of brain injury and CP than previously recognized ( MacLennan et al., 2015). Genes encoding processes related to catabolism of lipoprotein constituents, procoagulant factors, factors influencing central nervous system injury response, neuronal function (genes for potassium channels), cytoskeleton-interacting proteins, and adaptor proteins involved in intracellular trafficking are targets of further research as potential culprits of genetic causes for CP ( Fahey et al., 2016). For the purposes of this review, we will focus primarily on the neurologic correlates of gait abnormalities in CP and the implications for treatment.

Currently, brain imaging using MRI is the gold standard for identifying neural injury in CP. Recently, Fiori et al. (2015) developed an MRI score that correlated with severity of CP. In a review of six studies, including 1065 MRI and CT images in children diagnosed with CP, the most common injuries were WM injury (19-45% of images), GM injury (14-22%), focal vascular insults (10%), malformations (11%), and miscellaneous abnormalities (4-23%) ( Reid et al., 2014). WM injury was most common among all CP subtypes, though children with spastic diplegia had the highest rate of WM injury overall.

Brain Injury in Preterm Infants

Incidence and Risk Factors in Preterm Infants

Pregnancy complications are common in preterm birth (42% of cases, n = 92,320) and often contribute to a diagnosis of CP. Such complications include chorioamnionitis (11.2% absolute risk of CP), cervical conization (9.3%), placental abruption (8.7%), placenta previa (8.3%), congenital malformation (8.3%), prolonged rupture of membranes (7.5%), intrauterine growth restriction (7.1%), unspecified bleeding (6.8%), multiple births (5.7%), and pre-eclampsia (3.7%) ( Trønnes et al., 2014). Further, maternal infections during pregnancy (excluding the common cold, coughs, etc.) have been reported in 29.6% (118 of 400) of cases of CP ( Bax et al., 2006). Specifically, 19.2% of the mothers reported a urinary tract infection during pregnancy and 15.5% of women reported taking antibiotics during pregnancy. Twins have a greater risk of CP compared with singletons, especially if the pair have growth discordance ( Scher et al., 2002). In addition, the in utero death of one twin leaves the surviving infant at a tenfold increased risk for CP, as dispersed intravascular coagulation and emboli in the vascular anastomoses of the twin placenta likely contribute to prenatal cerebral injury in the surviving twin ( Scher et al., 2002; Nelson and Blair, 2015). Marked fetal growth restriction with presence of major birth defects is also associated with an increased risk of CP ( Decouflé et al., 2001; Blair and Nelson, 2015). In addition, sex differences in neurodevelopment have been identified: the incidence of moderate-to-severe CP was found by Hintz et al. (2015) to be 50% higher in males (10.7%) than in females (7.3%) in extremely low-birthweight (<1000 g) preterm infants. They found no measurable risk factors or events, including a diagnosis of intraventricular hemorrhage on ultrasound, that explained the sex differences in neurodevelopmental outcomes. Findings indicate a distinct disadvantage in male infants for developing CP that is exacerbated in the preterm population.

Mechanisms of Injury in Preterm Infants

The increased risk for infection/inflammation (including ischemia-induced inflammation) during fetal development also contributes to the mechanism of injury in PVL. Upregulation of pro-inflammatory cytokines and activation of microglia within immature WM results in damage to the vulnerable premyelinating oligodendrocytes. This cell-specific damage results in WM hypo-myelination, and necrotic microscopic lesions lead to proliferation of glial cells in response to injury, a common finding in non-cystic PVL and among preterm children with CP ( Graham et al., 2016). Mallard et al. (2013) suggested that the inflammation-induced opening of connexin hemichannels plays a pivotal role in initiating a cycle of excessive ATP release, over-activation of purinergic receptors on microglia and astrocytes, and subsequent brain damage.

After initial injury by hypoxia-ischemia and infection/inflammation, excitotoxicity and free radical attack by reactive oxygen and nitrogen species are the main downstream mechanisms of injury in PVL. Current evidence supports that oligodendroglial development is susceptible to oxidative attack within a maturation-dependent window of vulnerability. This window of vulnerability is due mainly to delayed development of antioxidant enzymes and the acquisition of iron for oligodendrocyte differentiation. Human brain studies have shown a delay in the development of superoxide dismutase (antioxidant) enzymes, e.g., manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase ( Folkerth et al., 2004). Further, observations show that developing WM uses iron both for oligodendrocyte differentiation ( Connor and Menzies, 1996) and to convert hydrogen peroxide to its hydroxyl radical, thereby resulting in the increased free iron levels in the cerebrospinal fluid of children with posthemorrhagic ventricular dilation ( Savman et al., 2001). Excitotoxicity likely leads to injury to premyelinating oligodendrocytes by promoting Ca ²⁺ influx and generation of reactive oxygen and nitrogen species. Glutamate is capable of inducing maturation-dependent death of premyelinating oligodendrocytes by receptor-mediated mechanisms in vivo ( Khwaja and Volpe, 2008). Premyelinating oligodendrocytes contain glutamate receptors that, when excessively activated, lead to cell injury. The excess glutamate comes from oligodendrocytes that express AMPA/kainate-type glutamate receptors and NMDA receptors, the over-activation of which results in cell death ( Káradóttir and Attwell, 2007; Khwaja and Volpe, 2008). In addition, the AMPA/ kainate receptors have been found to be upregulated in premyelinating oligodendrocytes rather than in mature oligodendrocytes ( Rosenberg et al., 2003; Jensen, 2005).

Patterns of Injury in Preterm Infants

Cortical GM and BGTL may occur in preterm children as a result of hypoxia-ischemia. Injury to the GM has been linked most frequently to spastic quadriplegic CP and dyskinetic CP ( Reid et al., 2014).

Preterm children may also have long-term reductions in regional brain volumes of the sensorimotor cortex, which are associated with poorer cognitive and visuomotor outcomes ( Peterson et al., 2000).

Postnatal Brain Injury in Preterm Infants

Brain Injury in Term-Born Infants

Incidence and Risk Factors in Term-Born Infants

Mechanisms of Injury in Term-Born Infants

Patterns of Injury in Term-Born Infants

Another pattern of injury present among term-born children with CP and hypoxic-ischemic injury is multicystic encephalopathy, which involves multiple large cystic cavities in the WM separated from each other by membranes and is associated with periventricular, subcortical, and cortical damage ( Sie et al., 2000).

Focal vascular insults are seen predominantly in term-born children with hemiplegic CP, whereas malformations tend to be associated with ataxic, quadriplegic, and diplegic CP ( Reid et al., 2014). Of these malformations, schizencephaly occurs more often in patients with spastic hemiplegia than in any other CP subtype ( Kulak et al., 2011).

Postnatal Brain Injury in Term-Born Infants

Neuromuscular Deficits of Cerebral Palsy

Neuromuscular deficits differ among spastic, dyskinetic, and ataxic CP and involve abnormal motor drive, muscle tone, motor patterns, and coordination caused by the original brain injury. In addition, subsequent sensorimotor and musculoskeletal changes result from chronic abnormal muscle activation, biomechanical imbalance around joints, neglect, and/or disuse. These factors, combined with rapid limb growth and increasing body weight in children, contribute to gait abnormalities in CP ( Meyns et al., 2016a).

Neuromuscular Deficits of Spastic CP

In spastic CP, neurological injury to the CST results in four interrelated neuromuscular deficits: muscle weakness, shortened muscle-tendon unit, spastic and passive resistance to stretch, and impaired SMC. These deficits arise from brain injury and subsequent changes in the motor unit, muscle growth, and muscle fiber composition. Further involvement of sensory-motor regions can impair proprioception and motor function ( Hoon et al., 2009). Together, these neuromuscular deficits result in the gait abnormalities commonly seen in children with spastic CP.

The motor unit is the functional unit of the motor system, consisting of a single motor neuron, the neuromuscular junction, and the muscle fibers innervated by the motor neuron. In the gastrocnemius, for example, a motor unit consists of a single motor neuron with approximately 2000 associated muscle fibers, whereas smaller muscles in the hand that are responsible for fine motor control have a much smaller muscle fiber-to-motor neuron ratio. Rose and McGill (2005) found reduced neuromuscular activation and motor-unit firing rates in the medial gastrocnemius and tibialis anterior in spastic CP. The altered neural input to muscle has been associated with altered muscle growth, fiber type and size variability, sarcomere length, as well as altered collagen, fat, and extracellular matrix composition. These changes in skeletal muscle morphology contribute to functional changes in muscle strength, the length of the muscle-tendon unit, and the reflexive and passive resistance to stretch.

Muscle fiber development and growth rely on a number of neuronal, nutritional, and hormonal factors, as well as initial and repeating patterns of muscle use ( Kimball and Jefferson, 2010; Braun and Gautel, 2011; Gundersen, 2011). Muscle growth increases rapidly during the prenatal and neonatal periods. For example, the sartorius muscle fibers double in diameter between mid-gestation and term ( Moore et al., 1971), and accelerated growth in overall muscle fiber diameter has been noted between 35 weeks of gestation and term ( Schloon et al., 1979). Thus, preterm delivery may interfere with early muscle growth, and compromised nutritional status in the preterm infant likely contributes to poor skeletal muscle growth ( Thorn et al., 2009). It has been shown that muscle size is reduced in spastic CP ( Barber et al., 2011), and muscle volume is especially reduced in the gastrocnemius and semitendinosus, both of which are critical for gait ( Smith et al., 2011). Recent work by Dayanidhi and Lieber (2014) suggests that satellite cells also play an important role in muscle growth. Muscle biopsies from children with CP had 60-70% fewer satellite cells when compared to that of age-matched, TD children, which may contribute to muscle contracture in CP.

Weakness in Spastic CP

Children with spastic CP suffer from significant weakness that contributes to abnormal posture and movement ( Brown et al., 1991; Damiano et al., 1995; Rose and McGill, 2005; Barber et al., 2012; Noble et al., 2014). Studies suggest that the loss of excitatory motor signals descending in the CST results in reduced muscle activation and reduced muscle size, which is aggravated further by pathological changes in the elasticity of the muscle ( Brown et al., 1991; Wiley and Damiano, 1998; Engsberg et al., 2000). MVC of the quadriceps, plantar flexors, and dorsiflexors are significantly reduced in CP ( Damiano et al., 2002; Elder et al., 2003; Rose and McGill, 2005; Stackhouse et al., 2005; Barber et al., 2012). Barber et al. (2012) found a 33% lower ankle plantarflexion torque in children with spastic CP compared to their TD peers. This reduced ankle plantarflexion torque was partially explained by 37% smaller medial gastrocnemius muscle and 4% greater antagonistic co-contraction.

It has been posited that individuals with spastic CP do not develop sufficient tension frequently enough to encourage normal muscular growth ( Noble et al., 2014). Noble et al. (2014) found that the medial and lateral gastrocnemius, soleus, tibialis anterior, rectus femoris, semimembranosus, and semitendinosus of patients with CP had reduced volumes compared to TD children, even when adjusted for body mass. This lack of growth may be mediated through reduced muscle and neurotrophic factors that are released in response to neuronal activation, acetylcholine release, and contraction ( Gough and Shortland, 2012), further contributing to weakness. Affected muscles in spastic CP have substantially reduced neuromuscular activation and strength ( Damiano et al., 2001; Rose and McGill, 2005; Stackhouse et al., 2005) and an inability to sufficiently recruit and drive motor-units at higher firing rates ( Rose and McGill, 2005). Further, musculoskeletal manifestations progress as skeletal growth out-paces muscle growth, leading to reduced muscle volumes associated with weakness ( Noble et al., 2014). Muscle endurance is also reduced in CP compared to TD individuals; specifically, adolescents with CP have a reduced capacity to endure activities at similar relative loads compared with TD adolescents ( Eken et al., 2014).

While the neural correlates of muscle weakness are not well studied, Meyns et al. (2016b) recently found a correlation between asymmetry in strength and asymmetry in the CST ADC calculated from DTI ( r = 0.639, p < 0.034) of the segment of the CST that runs through the posterior limb of the internal capsule (CST PLIC). Thus, greater asymmetry in strength was associated with a greater ADC asymmetry of the CST PLIC. Further research is needed to clarify the brain structure-function relations underlying weakness in spastic CP to develop effective treatments.

Short Muscle-Tendon Unit in Spastic CP

Impaired muscle growth and muscle fiber changes result in a shortened muscle-tendon unit in the muscles affected by spastic CP. The failure of muscle growth to keep pace with bone growth is most evident in the bi-articular muscles, e.g., the gastrocnemius, hamstrings, and rectus femoris, and contributes to joint contractures and gait abnormalities such as toe-walking and flexed-knee gait.

The short muscle-tendon unit also likely contributes to weakness. The active force generated by muscle is a function of the number of cross-bridges formed, which depends on the extent of myofilamentary overlap. Muscle force is maximal at intermediate muscle lengths with optimal myofilament overlap and declines at shorter and longer relative lengths ( Gordon et al., 1966). Thus, short muscles with lengthened sarcomeres, as has been found in spastic muscle in CP ( Lieber et al., 2004), may result in an inefficient overlap of myofilaments, thereby contributing to weakness. Research on the neural correlates of short muscle-tendon unit is needed, considering the impact of reduced descending excitatory signals on muscle growth, muscle-to-bone growth rate discrepancy, and muscle fiber diameter.

Spasticity in Spastic CP

Resistance to muscle stretch in children with spastic CP is primarily due to two factors: neural-mediated reflex stiffness (muscle spasticity) and passive muscle stiffness. Spasticity and passive resistance to muscle stretch particularly influence bi-articular muscles, such as the rectus femoris, hamstrings, and gastrocnemius, which require greater excursion across two joints.

Spasticity has been defined as "a velocity-dependent increase in muscle tone with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex" ( Mayer, 1997). Loss of descending inhibition of the stretch reflex pathway to affected muscles in spastic CP may result in increased sensitivity to stretch ( Rose and McGill, 1998).

In addition to the velocity-dependent sensitivity to stretch ( Sanger et al., 2003), spasticity may also be position-dependent. Wu et al. (2010) found that evaluating patients at different velocities and positions helped to distinguish passive stiffness from spasticity. The delayed catch angle at higher velocities may be due to position change, as the joint is moved into a stiffer position.

Although muscle spasticity is a primary symptom of spastic CP, objective quantification has been challenging ( Bar-On et al., 2014b). Recent data on the profile of imposed muscle accelerations, including the muscle length-velocity relationship, hold promise for quantifying spasticity. Bar-On et al. (2014c) quantified integrated biomechanical (joint position and torque) and electrophysiological (surface EMG) signals of manually performed passive stretches on the medial hamstrings and gastrocnemius and found that measurement reliability was moderately high for both muscles, and spasticity parameters were significantly higher in children with spastic CP than in TD children. Similarly, biomechanical parameters quantifying the neural and non-neural contributions to ankle joint torque were measured during manually applied passive stretches to the gastroc-soleus in children with spastic CP, and the parameters based on modeling of passive muscle stiffness and viscosity were able to detect a significant decrease in spasticity ( p = 0.012) following BoNT-A in 53 children with spastic CP ( Bar-On et al., 2014a). This type of musculoskeletal modeling combined with spasticity measurement may allow for individually tailored spasticity treatments. Further, investigation of fast and slow passive rotations imposed during manual and motorized assessments may yield greater insights into the development of movement profiles to better mimic spasticity imposed during functional tasks such as walking ( Sloot et al., 2016).

Increased passive muscle stiffness has been demonstrated in spastic CP. Lee et al. (2016) used shear wave elastography to measure muscle stiffness in eight children with hemiplegic CP and found that the more-affected limb had greater muscle stiffness than the less-affected limb. The increased passive mechanical stiffness accounted for nearly all of the measurable increase in joint stiffness ( Lieber et al., 2004), suggesting that spastic muscles have an altered resting sarcomere length and altered cellular elastic modulus. Smith et al. (2011) also found that the increased stiffness of hamstring contractures in children with spastic CP compared to age-matched, TD children was likely due to increased stiffness of the extracellular matrix and increased in vivo sarcomere length.

Neural correlates of spasticity are emerging. Serdaroglu et al. (2004) found PVL to be associated with spasticity. Specifically, spasticity was found in 54 of 69 participants with body PVL and in 7 of 20 without body PVL. Body PVL was defined as PVL injury in the WM adjacent to the middle region of the lateral ventricle. In addition, lower volume of the total corpus callosum as well as lower volume in the posterior aspect of the central corpus callosum correlated to increased incidence of spasticity ( Serdaroglu et al., 2004). Meyns et al. (2016b) recently found a correlation between asymmetry in spasticity and asymmetry in the CST ADC calculated from DTI ( r = 0.608, p < 0.048). Further study will clarify neural correlates and the mechanism underlying spastic and passive resistance in muscle stretch and guide more effective treatment.

Impaired Selective Motor Control in Spastic CP

Neuromuscular Deficits in Dyskinetic CP

Neuromuscular Deficits in Ataxic CP

Influence of Neuromuscular Deficits on Gait in Cerebral Palsy: Treatment Implications

Neuromuscular deficits of spastic, dyskinetic, and ataxic CP differ and therefore influence gait in different ways. Neuromuscular deficits include abnormal motor drive, muscle tone, motor patterns, coordination, and sensorimotor impairments caused by the original brain injury. Subsequent sensorimotor and musculoskeletal changes also contribute to gait abnormalities in children with CP.

The Influence of Neuromuscular Deficits in Spastic CP

The neuromuscular deficits of spastic CP, including muscle weakness, short muscle-tendon length, spasticity, and impaired SMC influence gait in different but predictable ways and contribute to common gait abnormalities such as plantar-flexed gait, flexed-knee gait, or a stiff-knee gait. Plantar-flexed gait includes both 'drop-foot' gait where weakness of the tibialis anterior prevents adequate dorsiflexion in swing phase, as well as equinus gait which arises from short and/or spastic plantar-flexors and impacts both stance and swing phases of the gait (Figure 3 and Table 2). In both cases there is typically forefoot initial contact and disruption of the normal heel-toe progression of gait. The plantarflexed position of the ankle causes an early and 'double bump' plantarflexion moment that reduces forward momentum. Additionally, the plantarflexed position results in reduced foot contact area in stance that can impair balance.

Stiff-knee gait arises from spastic knee extensors which impair pre-swing mechanics that limit knee flexion in early swing. In addition, hip flexor weakness impairs hip and knee flexion in early swing, and impaired SMC slows the transition from the stance phase hip and knee extension to the swing phase hip and knee flexion. The neuromuscular deficits contributing to stiff-knee gait primarily impact pre-swing through mid-swing phases of gait in spastic CP (Figure 3 and Table 2). Here, we explore the influence of neuromuscular deficits on gait in the three types of CP with a focus on spastic CP.

The Influence of Weakness on Gait in Spastic CP: Treatment Considerations

The impact of weakness in spastic CP most notably affects ankle dorsiflexion in swing phase and hip and knee extension in stance phase. Thus, weakness affects all phases of the gait cycle (Figure 3 and Table 2). Weak ankle dorsiflexors result in excessive ankle plantar flexion in swing and poor foot clearance with compensatory motion such as hip circumduction to clear the foot. Weak ankle dorsiflexors also cause excessive plantar flexion at initial contact, disrupting the normal heel-toe progression of gait. Weak plantar flexors fail to restrain tibial forward rotation over the foot in mid stance, increasing hip and knee flexion in stance. Furthermore, failure to stabilize the ankle during heel rise reduces the normal ankle plantar-flexion moment in terminal stance and can decrease peak knee flexion in swing. Weak hip and knee extensors contribute to flexed hip and knee postures during the stance phase of gait. Weak hip flexors can contribute to reduced peak knee flexion in swing. Weak hip abductors cause contralateral pelvic drop and increase ipsilateral trunk sway, shifting the body's center of mass closer to the hips' axis of rotation and thereby reducing the muscular demand on the hip abductors.

The Influence of Short Muscle-Tendon Units on Gait in Spastic CP: Treatment Considerations

The Influence of Spasticity on Gait in Spastic CP: Treatment Considerations

Treatments for spasticity include BoNT-A injections, oral or intrathecal baclofen, and dorsal rhizotomy. However, treatments that promote strength may also be effective. A study conducted by Williams et al. (2013) found that simultaneous use of BoNT-A and strength training was successful in spasticity reduction, improving strength, and achieving functional goals, over and above treatment with BoNT-A alone in 15 children (aged 5-12 years) with spastic diplegic CP. Further research is needed to assess the efficacy of treatments that promote strength, such as intensive strength training and functional electrical stimulation, for reducing spasticity and improving overall gait function.

The Influence of Impaired Selective Motor Control on Gait in Spastic CP: Treatment Considerations

Recently, Shuman et al. (2016) examined EMG patterns of muscle activation during gait in CP and found increased patterns of muscle synergies. They developed an EMG analysis to quantify synergy patterns during gait and found that prolonged antigravity muscle activation is necessary to prevent collapse in flexed-knee gait. However, prolonged and simultaneous antigravity muscle activation may be a compensatory symptom, separate from impaired SMC and therefore requires further delineation.

Treatments utilizing intensive exercise patterns outside of synergy patterns, such as knee extension combined with ankle dorsiflexion, may prove beneficial and warrant further investigation. Research is needed to determine the efficacy of intensive exercise on improving SMC using exercise patterns that combine flexion and extension of adjacent joints. Further work is needed to determine if improvements in SMC translates to improved gait patterns.

The Influence of Neuromuscular Deficits on Gait in Dyskinetic CP

Deep brain stimulation to the globus pallidus internus may be an effective treatment option for children with dyskinetic CP (Review: Koy et al., 2013). It has been shown that response to pallidal deep brain stimulation in the treatment of dystonia yields better outcomes if administered earlier in life (<7 years of age) ( Lumsden et al., 2013), highlighting a need for early intervention.

The Influence of Neuromuscular Deficits on Gait in Ataxic CP

Neural Correlates of Gait Abnormalities in CP

To date, few studies have examined the neural correlates of motor deficits and gait abnormalities. Staudt et al. (2003) found correlations ( r = 0.8; p < 0.01) between lower limb motor dysfunction assessed with the Movement ABC and extent of contralateral PVL, as assessed on semi-coronal reconstructions from 3D-MRI in 13 adolescents with CP. In addition, Rademaker et al. (2004) found an inverse association between motor function assessed on Movement ABC scores and corpus callosum area assessed on MRI in 204 preterm children with VLBW. The association existed in frontal, middle, and posterior corpus callosum areas but increased in the direction of the posterior part. Lee et al. (2011) found a strong relationship between motor dysfunction assessed with GMFCS and fractional anisotropy values assessed on DTI within the bilateral CST and posterior body of the corpus callosum ( p < 0.03); Cortical volume of the pre- and post-central gyri, and the paracentral lobule was negatively associated with GMFCS levels ( p < 0.005).

Meyns et al. (2016b) found that the severity of gait abnormality assessed using the Gait Profile Score correlated to total corpus callosum ( r = -0.441; p < 0.040) and subpart 1 ( r = -0.437; p < 0.042) volumes in children with CP ( Witelson, 1989). Furthermore, Rose et al. (2007) found evidence to support early prognosis of gait abnormalities in VLBW preterm children. They found that neonatal WM microstructure of the posterior limbs of the internal capsule assessed with DTI fractional anisotropy correlated to severity of gait abnormalities at 4 years of age, measured using 3D kinematics ( r = 0.89, p < 0.0) and to GMFCS ( r = 0.65, p < 0.04). In a separate cohort of VLBW preterm children, gait velocity at 18-22 months of age correlated ( r = -0.374, p < 0.007) with near term brain microstructure in the genu of the corpus callosum assessed on DTI mean diffusivity ( Rose and McGill, 1998).

Conclusion

Emerging evidence suggest that important links exist between neurologic injury, neuromuscular deficits, and specific gait abnormalities in CP. A better understanding of these relationships can elucidate underlying mechanisms of gait impairments and lead to more strategic treatments. Here, we have reviewed the nature of brain injuries in CP, the associated neuromuscular deficits, and the subsequent gait abnormalities on both a microscopic and functional level.

Our understanding of brain abnormalities in CP have been informed by rapidly evolving neuroimaging techniques. However, inconsistent methodology and reporting of data limit interpretation. These discrepancies have been identified as "(1) inappropriate assignment of etiology to morphologic findings, (2) inconsistent descriptions of radiologic findings, (3) uncertain relationship of pathologic findings to brain insult timing estimates, and (4) study designs that are not based on generalizable samples" ( Korzeniewski et al., 2008). In addition, consistent, standardized language across studies would help compare findings in context of the existing body of knowledge. Neuroimaging findings are rarely reported with anatomical descriptions sufficient for direct comparison between studies. For example, the localization of atrophy of GM or WM, the location of cavities, and the nature of anomalies found on imaging are not specified in a consistent manner. However, the National Institute of Neurological Disorders and Stroke (NINDS), in conjunction with the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) have recently developed a set of Common Data Elements for use in CP research, including neuroimaging diagnostics, which promises to standardize clinical language and improve data collection consistency for future research on CP ( Odenkirchen et al., 2016).

The criteria for estimating the time of injury are also not well described; thus, exactly how prenatal and perinatal insults are differentiated is unclear, and there is a need to develop accurate, standardized techniques. Automated analysis of MRI is an exciting new field that can facilitate precise identification of brain abnormalities and improve consistency in the interpretation of MRI scans. Automated brain lesion segmentation using the Least Absolute Shrinkage and Selection Operator (LASSO) on both WM and GM from T1-weighted MRI sequences was recently validated against manual expert classifications of lesions ( Pagnozzi et al., 2016). The prognostic ability of MRI to determine mild motor impairment and exactly which motor functions will be compromised is still limited. Thus, further work on developing a quantitative relationship between lesion burden and functional outcome will help increase the utility of structural MRI in predicting individual prognoses and planning targeted therapeutic interventions.

By discussing the neurologic correlates of gait abnormalities within this context, we hope to encourage the reader to recognize specific mechanisms of gait abnormalities in CP and discover targeted treatment opportunities that can substantially improve functional outcomes for children with CP.

Author Contributions

JZ, EB, and JR synthesized literature and wrote the paper. All authors discussed and commented on the manuscript.

Funding

This work was supported in part by MedScholars Fellowship Stanford University.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgment

We wish to thank Katelyn Cahill-Rowley, Kornél Schadl and MaryAnn Wijtman for helping to create Figure 1.

Abbreviation

ADC, apparent diffusion coefficient; ATP, adenosine triphosphate; BGTL, basal ganglia and/or thalamus lesions; BoNT-A, botulinum toxin-A; CP, cerebral palsy; CST, corticospinal tract; CT, computed tomography; DTI, diffusion tensor imaging; EMG, electromyography; GM, gray matter; GMFCS, Gross Motor Function Classification Scale; MRI, magnetic resonance imaging; MVC, maximal voluntary contraction; PVL, periventricular leukomalacia; SCALE, Selective Control Assessment of the Lower Extremity; SMC, selective motor control; TD, typically developing; VLBW, very low birthweight; WM, white matter.

References

Australian Cerebral Palsy Register Report [ACP] (2013). Report of the Australian Cerebral Palsy Register, Birth Years 1993-2006. Sydney: Cerebral Palsy Alliance Research Institute.
Google Scholar
Mtui, E., Gruener, G., and Dockery, P. (2016). FitzGerald's Clinical Neuroanatomy and Neuroscience, 7th Edn. Philadelphia, PA: Elsevier Health Sciences.
Google Scholar
Odenkirchen, J., Burr, T., Ala'i, S., Esterlitz, J., and Feldman, R. (2016). "Common language for clinical research studies: the national institute of neurological disorders and stroke and american academy for cerebral palsy and developmental medicine common data elements version 1.0 recommendations," in Proceedings of the American Academy for Cerebral Palsy and Developmental Medicine Annual Meeting, September 20-24, 2016, Hollywood, FL.
Google Scholar
Sanger, T. D. (2015). Movement disorders in cerebral palsy. J. Pediatr. Neurol. 13, 198-207.
Google Scholar
Schnekenberg, R. P., Perkins, E. M., Miller, J. W., Davies, W. I., D'Adamo, M. C., Pessia, M., et al. (2015). De novo point mutations in patients diagnosed with ataxic cerebral palsy. Brain 138, 1817-1832. doi: 10.1093/brain/awv117

# data[].attributes.attachment_link.title
Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

# data[].attributes.attachment_link.description
Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children.

# data[].attributes.body
This is the least common form of CP. This is due to damage to the cerebellum.

How does Ataxic CP affect you?

unsteady, shaky movements or tremors

struggle with maintaining balance

sense of balance and depth perception is affected

can affect upper and lower limbs

may cause slow eye movements

How does Ataxic CP affect speech?

can affect speech and swallowing

monotone voice with a breathy sound

unusually pauses and accelerations between syllables

# data[].attributes.attachment_link.provider_name
Centers for Disease Control and Prevention

# data[].attributes.attachment_link.description
Cerebral palsy (CP) is the most common motor disability in childhood. Learn more facts.

# data[].attributes.body
This is due to damage to the basal ganglia, it is involuntary movement.

How does dyskinetic CP affect you?

Dystonia- twisting and repetitive movements

repetitive movements

rapid or slow movements that are often painful

attempts at controlled movements trigger involuntary movements

involuntary movements are more common when you are tired, stressed, anxious

Slow "stormy" movements- athetosis

slow, writhing movements that usually affect the hands, feet, arms or legs

difficulty with eating or drinking

grimacing and drooling

small or big unwanted movements

dance-like irregular, unpredictable movements- chorea

involuntary movements- these are brief, abrupt and unpredictable

those with mild cases may simply appear clumsy

those with severe cases may have wild/violent movements

interfere with movement, speech and swallowing

How does dyskinetic CP affect speech?

difficulty controlling lips and tongue

difficulty with eating and drinking

difficulty verbalizing thoughts

# data[].attributes.attachment_link.title
Functional outcomes in children and young people with dyskinetic cerebral palsy

# data[].attributes.attachment_link.title
Spastic Cerebral Palsy Surgical and Rehabilitation Treatment | Journee’s Story

# data[].attributes.body
This is a form of spasticity that affects one side of the body. One arm and one leg on the same side of the body is affected.

How does hemiplegia affect you?

difficulties with balance and walking

struggles with fine motor skills

muscle stiffness on one side of the body

jerky/shaking muscles

weakness on one side of the body

delays in developmental milestones

How does hemiplegia affect speech?

speech that is slow and slurred

speech that is difficult to understand

difficulty controlling pitch, loudness, rhythm, and voice qualities of their speech

# data[].attributes.attachment_link.readable_text
What is Hemiplegia?

Hemiplegia in infants and children is a type of Cerebral Palsy that results from damage to the part (hemisphere) of the brain that controls muscle movements. This damage may occur before, during or shortly after birth.

The term hemiplegia means that the paralysis is on one vertical half of the body. A similar medical term, hemiparesis, means a weakness on one side of the body. In children with hemiplegia, the paralysis in the body occurs on the side opposite the affected part of the brain. For example, if the left side of the child's brain is injured, then the paralysis will be on the right side of the child's body.

What are the Symptoms Of Hemiplegia in a Child?

The symptoms of spastic hemiplegic cerebral palsy may differ from child to child and over time. Symptoms may include:

stiffness and weakness in muscles on one side of the body

only using one hand during play or favoring one hand before the age of 3 years

keeping one hand in a fist

difficulty with walking and balance

difficulty with fine motor tasks like writing or using scissors

delay in reaching expected developmental milestones such as rolling over, sitting up, crawling, or smiling

What are some of the Conditions Related to Hemiplegia in a Child?

Hemiplegia is often the result of a brain injury. A wide range of physical, cognitive, and behavioral effects can result from a brain injury. Each child is different and your child may or may not have some of the following effects of the brain injury:

Memory - Difficulty with encoding, storing, and retrieving new information.

Attention and Concentration - Problems focusing and sustaining attention for along periods of time. She may be unable to filter out distractions in the classroom or may have problems functioning in situations where there is a great deal of noice or stimluation. The child may have difficult switching from one topic or activity to another.

Executive Functions - Difficulty setting appropriate goals, planning and organizing behavior to accomplish tasks, and monitoring and evaluating behavior.

Speech and Language - Depending on the age and cause of injury, the child may have problems with speech, such as lack of speech or extremely slow speech. These may improve with time. Children who have a focal injury(stroke) at or near birth, may have delays in expressive language (talking), but not in receptive language (understanding). These children often begin to catch up with peers by age 3 or so.

Social Communiation - The ability to participate in conversation with others requires the use of cognitive, linguistic, and social skills, all of which can be affected by an early brain injury. The child may have difficulty following shifting topics, interpretation of social cues, organization of ideas, and application of rules of social behavior.

Behavior - May experience agitation, irritability, mood swings, hyperactivity, apathy and emotional and behavioral outbursts as a result of the brain injury. The psychosocial problems can be extremely complex.

Sensory Effects - Difficulty with vision and impaired coordination of both eyes. The brain's visual processing area may be injured, resulting in visual field cuts (partial losses of vision). Hearing may also be affected.

Seizures - May develop immediately following the injury or months or even years later. In many cases, the seizures can be controlled through medication.

See the Medical section of the CHASA website for additional information.

Is Hemiplegia a Progressive Condition?

No hemiplegia is not a progressive condition, nor is it a disease. As children experience growth spurts, they may have more problems with muscle spasticity, but this does not mean that the initial injury has gotten worse.

Children with hemiplegia tend to show some atrophy of the hand, arm, shoulder, leg, and foot. This appears more noticeable as the child reaches his or her teens. The child's arm and leg on the affected side are often shorter than the other side. Some of this may be a true difference in the length of the bone. The limb may also "appear" shorter, but this appearance is not a true length difference and is actually due to the increased muscle tone pulling the limb upwards. Weight bearing and strengthening exercies may help prevent atrophy and increase use.

Children with hemiplegia are at a higher risk of developing scoliosis. It is recommended that your child be followed by an orthopedic surgeon or physiatrist so they can watch for signs of scoliosis and treat if necessary.

Are There Treatments For Children With Hemiplegia?

Children with hemiplegia cannot be "cured", but therapies can help with some of the symptoms. Medication can be prescribed for seizures. Orthotics, braces, and splints may help with spasticity and gait (walking). See the Treatment section of the CHASA website for more information.

For more detailed information, read Hemiplegia in Children by John Lynch, DO, NINDS

Will my Child with Hemiplegia be in a Special Education Program at School?

Most children with hemiplegia attend traditional schools and are integrated into a traditional classroom. Some children may be pulled out of class or have a special teacher who comes into class to help with challenging subjects. Other children may be in smaller non-integrated classrooms if those better fit their needs. See the School section of the CHASA website for more information.

Causes of Hemiplegia in Children

Cerebrovascular Accident (CVA) or stroke

Intraventricular Hemorrhage of the newborn (IVH)

Thrombosis: embolism or hemorrhage

Transient ischemic attack (TIA)

Migraine syndrome

Head Trauma: brain contusion, subdural hematoma or epidural hematoma

Sturge-Weber Syndrome

Todd's Paralysis

Brain tumor (Primary or metastatic disease)

Infection: brain abscess, encephalitis, subdural empyema or meningitis

Nonketotic hyperosmolar coma

Vasculitis

Demyelinating disease: multiple sclerosis, acute necrotizing myelitis

Hereditary disease: leukodystrophies

Congenital or perinatal injury

Arterovenous malformations

Unilateral Polymicrogyria

Unilateral Perisylvian Syndrome

Hemimegalencephaly leading to hemispherectomy

Hemimegalencephaly with Ohtahara syndrome leading to hemispherectomy

Unilateral Hydrocephalus

Cerebral Cavernous Malformations

Bleed due to Extracorporeal Membrane Oxygenation (ECMO)

Unilateral Cortical Displasia/Hemimegalencephaly leading to hemispherectomy

Schizencephaly

Other Resources for Children with Hemiplegia or Hemiparesis
Hemi-Kids Support Group for Parents of Children with Hemiplegia
Hemiplegia/Hemiparesis discussion of gait by Molson Medical Informatics

Congenital Hemiplegia book published 2001; edited by Brian Neville, Robert Goodman
Supporting young adults with hemiplegia: services and costs
Cerebral palsy after perinatal arterial ischemic stroke. March 2008. Indiana

Fingertip force control during bimanual object lifting in hemiplegic cerebral palsy. March 2008, The Netherlands.

Fast adjustments of ongoing movements in hemiparetic cerebral palsy

Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study. Jan. 1999. London. Early MRI and EEG can help to identify the infants with cerebral infarction who are likely to develop hemiplegia.

Hemiparetic cerebral palsy: etiological risk factors and neuroimaging journal article 2001

Visual function in children with hemiplegia in the first years of life 2001

The relationship between infections and adverse pregnancy outcomes: an overview, Dec. 2001

Premotor cortex is involved in restoration of gait in stroke, Aug. 2002

Intact motor imagery in chronic upper limb hemiplegics: evidence for activity-independent action representations, Aug. 2002

Comparing tests of tactile sensibility: aspects relevant to testing children with spastic hemiplegia. Sept. 2002. Sweden.

Neuroimaging fails to identify asymptomatic carriers of familial porencephaly. Belgium. October 2002

Hand function in children with hemiplegic cerebral palsy: prospective follow-up and functional outcome in adolescence. Italy. Feb. 2003

# data[].attributes.attachment_link.description
What is Hemiplegia? Hemiplegia in infants and children is a type of Cerebral Palsy that results from damage to the part (hemisphere) of the brain that controls muscle movements. This damage may occur before, during or shortly after birth. The ...

# data[].attributes.body
This impacts the legs for the most part and occasionally the arms. Symptoms can be seen during infancy and early childhood. The most common problem here is muscle stiffness which can make crawling and walking extremely difficult for children.

How does diplegia affect you?

both arms are affected

legs may turn inward and cross at the knees

toe walking

flexed knees

later motor milestones

some children may not be able to walk at all

How does diplegia affect speech?

no significant difference in expressive and receptive language

# data[].attributes.body
This is the most severe of the three types of spastic cerebral palsy. It means "loss of use of the whole body"- the inability to control legs, arms, and body. This is typically caused by brain damage before, during or after birth.

How does quadriplegia affect you?

muscle tremors

seizures

cognitive disabilities

muscle tightness and spasticity

language disorders

joints that cannot stretch or move

muscles that rapidly contract and release

How does quadriplegia affect speech?

difficulty coordinating muscles of the face and tongue

difficulty swallowing

may cause speech impediments and language disorders

# data[].attributes.body
This is the most common type of cerebral palsy, when ones muscles appear tight and stiff.

How does spasticity affect you:

Upper limbs (arms and hands)

Flexion at the elbow

Flexion at the wrist

Flexion at the fingers

Lower limbs

flexion at the hip

adduction of the thighs

flexion at the knees

Equinovarus foot posture

Hyperextension of the big toe

How does spasticity affect speech?

slow imprecise oral movements that require a lot of effort

slurred speech sounds

A hoarse or tight sounding voice

# data[].attributes.attachment_link.title
Cerebral Palsy | Cook Children's Movement Disorders

# data[].attributes.attachment_link.description
The neurologists at Cook Children's Medical Center are experts in the treatment and care of cerebral palsy.