Disorders of Motor and Mental Development

Toni S. Pearson

Reet K. Sidhu

INTRODUCTION

Infancy and early childhood are marked by rapid brain growth and development. A wide variety of genetic and nongenetic factors may affect the immature brain during this period and manifest as a delay in the acquisition of milestones in one or more developmental domains: motor (gross and fine), speech/language, social, and cognitive. The delay may be isolated to one domain. When development in more than one domain is significantly delayed in children younger than the age of 5 years, the term global developmental delay applies.

Developmental delay is a common reason for referral to a child neurologist. The aims of the initial neurologic evaluation of a child with developmental delay are, first, to confirm the nature and severity of the suspected delay and second, to characterize any specific findings that may provide a clue to the underlying diagnosis. A detailed history is the key starting point. Items of particular importance include the family history (presence of neurologic or developmental disorders in the siblings, parents, grandparents, aunts, or uncles), perinatal history (complications during pregnancy, birth, or the neonatal period, including prematurity), and history of any coexisting medical problems. With regard to the presenting problem (e.g., motor delay), important items include the age at which the initial concern arose, the child’s developmental progress over time, and whether or not there has been developmental regression. On general examination, the child’s head circumference, height and weight, and the presence of any dysmorphic features should be noted. The eyes and optic fundi should be thoroughly examined, and skin should be checked for stigmata of neurocutaneous syndromes. Specific features of interest in the neurologic examination will be outlined in the relevant sections below.

DISORDERS OF MOTOR DEVELOPMENT

The acquisition of motor skills features prominently in the first year of life (Table 137.1). As a result, conditions that affect the motor system often present during infancy with motor developmental delay. Motor delay may also be the first manifestation of a condition that affects development globally because impaired motor function becomes apparent earlier than impairments in other domains such as cognition and language. Motor delay may be accompanied by specific motor symptoms such as stiffness, floppiness, and involuntary movements.

APPROACH TO THE CHILD WITH MOTOR DELAY

The neurologic examination begins with observation, particularly in the infant or toddler. Observe the child’s spontaneous posture and movements for asymmetry, paucity of movement that may hint at weakness, abnormal postures, and excessive or involuntary movements. On cranial nerve examination, look for eye movement abnormalities including restricted range of movement and nystagmus. If the child can speak, note whether speech is clear or dysarthric. Turning attention to the body, assess muscle tone in the trunk and limbs. Low truncal tone is common to many disorders that present with motor delay in infancy. Are the limbs hypotonic or spastic? Check whether tendon reflexes are abnormally brisk, suggesting an upper motor neuron lesion, or reduced, suggesting a neuromuscular abnormality. Assess coordination on targeted reaching movements (looking for dysmetria) and, in an older child, rapid alternating movements such as repetitive hand tapping. If the child is able, ask them to rise to standing from the floor (looking for a Gowers sign, which indicates proximal lower limb weakness). Note whether the gait is narrow or wide based and steady or unsteady. If involuntary movements are present, note their body distribution, their quality (e.g., sustained, writhing, or jerky), whether they are random or repetitive and stereotyped, and in what contexts they appear (e.g., at rest, during movement).

Following the clinical evaluation, brain imaging may be considered. Magnetic resonance imaging of the brain is indicated if there is a history of developmental regression, marked micro- or
macrocephaly (>2 standard deviations from the mean), abnormal rate of head growth, or any abnormalities on neurologic examination including cranial nerve dysfunction, focal weakness, spasticity, abnormally brisk reflexes, or involuntary movements. Other investigations, such as genetic testing, may be indicated by the clinical syndrome or brain imaging results. In all cases, the aim is to determine a specific etiologic diagnosis whenever possible in order to guide the most appropriate management strategy. If the clinical syndrome and brain imaging findings are compatible with a developmental malformation or static brain lesion, then symptomatic management will be the most important consideration (see “Cerebral Palsy” below). On the other hand, several individually rare genetic and metabolic disorders may present with motor delay and mimic cerebral palsy. It is vital that the child neurologist be alert to signs that may indicate one of these conditions (Table 137.2). Making the correct diagnosis in these selected cases has important implications for management. In some cases, there is a disease-specific treatment that may dramatically improve the clinical course. Even if no disease-specific treatment yet exists, accurate diagnosis makes it possible to provide prognostic information and genetic counseling regarding recurrence risk in future pregnancies to the family.

TABLE 137.1 Motor Developmental Milestones in the First 5 Years

Gross Motor	Age Range
Hold head steady	2-4 mo
Roll over	2-5 mo
Sit without support	5½-7 mo
Pull to stand	8-10 mo
Walk	11-15 mo
Run	14-20 mo
Jump	21-28 mo
Hop	3-4 yr
Balance on one foot for 4 s	3½-5 yr
Fine Motor	Age Range
Grasp rattle	3-4 mo
Reach	4-6 mo
Transfer objects	5-8 mo
Pincer grasp	7-10 mo
Scribble	12-17 mo
Feed self with spoon	13-18 mo
Stack two blocks	13-21 mo
Hold crayon using fingers (not fist)	2-3 yr
Copy a circle	3-4 yr
Refined tripod pencil grip, print own name, copy a square	4-5 yr
Age range indicates approximately the 25th to 90th percentile for each milestone according to the Denver II Developmental Screening Tool.

TABLE 137.2 Features that Should Prompt Evaluation for a Possible Genetic or Metabolic Disorder in a Child Presenting with Symptoms of Cerebral Palsy

Parent or sibling with a neurologic disorder

Absent history of perinatal complications

Normal brain imaging

Developmental regression

Progressive neurologic symptoms

Ataxia or involuntary movements

Signs of peripheral neuromuscular disease (reduced or absent reflexes, sensory loss)

Fluctuating motor symptoms, for example, diurnal variation, worsening during fasting or exercise (may be symptoms of a treatable condition, e.g., a neurotransmitter disorder or Glut1 deficiency syndrome)

CEREBRAL PALSY

Cerebral palsy (CP) is an umbrella term that describes a group of disorders characterized by motor impairment due to a developmental anomaly or nonprogressive lesion that arose in the developing fetal or infant brain. CP is not a specific disease and does not imply any one specific etiology. The term remains useful if considered not as a diagnosis in itself, but rather as a descriptive term which has widespread familiarity and conveys a recognized set of clinical characteristics and physical needs.

CP is common, with a birth prevalence of 2 or 3 per 1,000 live births in developed countries. Risk factors include a perinatal history of prematurity, intrauterine growth retardation, multiple gestation, and antepartum hemorrhage. One common misconception is that CP is usually caused by birth asphyxia, but in fact, fewer than 20% of patients with CP have documented perinatal asphyxia in many studies, and the actual proportion may be less than 10%. Other causes of CP include periventricular leukomalacia (the most common form of ischemic brain injury in very preterm infants), cerebral malformations, stroke, and infection. The etiology is usually, but not always, evident on brain imaging.

CP may be classified according to the predominant motor abnormality: spasticity, dyskinesia (involuntary movements including dystonia, chorea, or athetosis), or ataxia. In some cases, there is a mixture of more than one motor feature, such as spasticity and dystonia. Spastic CP may be further classified according to the affected body regions: diplegia (both legs), quadriplegia (all four limbs), and hemiplegia (one side of the body). An accurate characterization of the motor syndrome is important for two reasons. First, it assists the interpretation of the clinical history and brain imaging findings in establishing the etiology of a child’s CP. Second, it guides management decisions.

Spastic Diplegia

Approximately one-third of children with CP have spastic diplegia (or diparesis), in which spasticity is predominantly found in the legs. The arms may be mildly affected or unaffected. Parents may notice leg stiffness and a tendency for the legs to cross (“scissoring”) due to increased tone in the hip adductor muscles. The increased lower limb tone may lead an infant to roll over or bear weight through the legs at an atypically early age. An older child with mild to moderate symptoms may have a narrow-based, scissoring gait and toe walking. On examination, there is increased tone in the lower limb muscle groups, particularly hip adductors, hamstrings, and calves. Tendon reflexes are brisk and plantar responses are extensor. The most commonly associated brain imaging abnormality is bilateral periventricular white matter lesions, particularly in children with a history of prematurity. The white matter lesions may be periventricular leukomalacia, consequences of intraventricular hemorrhage, or both.

Spastic Quadriplegia

Spastic quadriplegia (found in 20% to 25% of children with CP) is the most severe form. It is frequently associated with diffuse brain injury or dysgenesis. Brain imaging may demonstrate abnormalities in both gray and white matter, such as cystic encephalomalacia resulting from diffuse hypoxic injury. Severe limb hypertonia is often associated with hypotonia in the neck and trunk. A subset of patients has lesions in the deep gray nuclei (basal ganglia or thalamus) and may have a coexisting movement disorder. Most children with spastic quadriplegia are unable to walk and are dependent on a wheelchair for mobility and on support from caregivers for routine daily activities. Due to the diffuse nature of the cerebral insult, a number of comorbidities are often present, including seizures, cognitive impairment, and swallowing and speech difficulties. If swallowing is impaired, a feeding gastrostomy is often required to ensure adequate nutrition. For children who have both the inability to speak and limited voluntary control of hand movements, communication can be very challenging. Effective use of a communication device such as a board or tablet to which the child can point, or devices with eye tracking capability, may vastly improve the quality of life for both the child and their caregivers.

Spastic Hemiparesis

Spastic hemiplegia is found in about one-third of children with CP and results from a unilateral corticospinal tract lesion, such as a cerebral infarct (often in the territory of the middle cerebral artery), focal malformation (e.g., schizencephaly, cortical dysplasia), or posthemorrhagic porencephalic lesion in the white matter.
Such lesions may have been acquired prenatally or perinatally, but symptoms tend to manifest around age 6 months, when parents notice that the child exhibits a strong preference to use one hand over the other. Handedness normally develops at age 2 to 3 years, and so an obvious hand preference younger than 12 months of age should prompt clinical evaluation for a hemiparesis.

The hemiparesis usually affects the arm and hand more than the leg. Children with spastic hemiplegic CP are able to walk, although walking may be delayed, and an asymmetric gait pattern with toe walking and circumduction of the affected leg on the affected side is observed. In mild cases, upper limb weakness may only be evident as a subtle loss of hand dexterity or abnormal arm posturing during running. On the other hand, large lesions that involve both the white matter and the cortex can be associated with pronounced weakness as well as cortical sensory loss, leading to little or no functional hand use. Speech and language development is often delayed in the setting of a unilateral lesion of either hemisphere, but most children develop age-appropriate spoken language by the time they enter school. Longitudinal follow-up studies describe the emergence of subtle cognitive weaknesses in school-aged children with a history of perinatal stroke. Seizures are an additional factor that may adversely impact long-term cognitive outcome.

Dyskinetic Cerebral Palsy

Involuntary movements are the predominant motor finding in 5% to 10% of children with CP. The majority of children with dyskinetic CP have a history of term birth. Several types of involuntary movements may occur either alone or in combination. Dystonia describes stereotyped, abnormal twisting postures that may be fixed or intermittent. When severe dystonia causes fixed postures that make the limb appear hypertonic, it may be difficult to distinguish from severe spasticity. Athetosis refers to continuous writhing or wriggly movements, whereas chorea appears as discrete, random-appearing, jerky movements. Children with dyskinetic CP often have a history of hypotonia during early infancy, and their underlying muscle tone also tends to be low. A key feature of the involuntary movements is their tendency to worsen with increased activity or attempts to initiate voluntary movement. Often, muscles of the face and neck are involved in addition to the trunk and limbs.

TABLE 137.3 Selected Genetic Conditions that May Mimic Dyskinetic and Attaxic Cerebral Palsy

Condition	Features
Neurotransmitter disorders	Hypotonia, dystonia with diurnal variation (better in morning and after sleep), oculogyric crises. Diagnosed by CSF neurotransmitter metabolite assay, genetic testing. Many forms respond to levodopa treatment.
Glut1 deficiency syndrome	Seizures, acquired microcephaly, ataxia, spasticity, dystonia, paroxysmal dyskinesia (may be triggered by exercise, fasting); treatment: ketogenic diet
Creatine deficiency	Intellectual disability, seizures, autism, progressive dystonia in guanidinoacetate methyltransferase (GAMT) deficiency. Treated with creatine monohydrate supplementation.
Benign hereditary chorea	Hypotonia, chorea, dystonia, myoclonus; may be associated with hypothyroidism, neonatal respiratory distress, or asthma.
Lesch-Nyhan syndrome	Hypotonia, dystonia, self-injurious behavior, elevated plasma urate
Ataxia-telangiectasia	Slowly progressive ataxia; chorea; dystonia (involuntary movements may preceed onset of ataxia); oculocutaneous telangiectasia; immunodeficiency; elevated serum α-fetoprotein; reduced levels of serum IgA, IgE, IgG₂
Pelizaeus-Merzbacher disease	Initial hypotonia then spastic quadriparesis, ataxia, ± dystonia and chorea, nystagmus (in classic form)
Niemann-Pick disease type C	Initial hypotonia followed by vertical supranuclear gaze palsy, slowly progressive ataxia, dystonia; ± hepatosplenomegaly
CSF, cerebrospinal fluid; Ig, immunoglobulin.

Basal ganglia lesions are the most common abnormality seen on brain imaging in children with dyskinetic CP. These lesions may result from hypoxic-ischemic injury (in which cortical injury is also often seen) or neonatal hyperbilirubinemia (kernicterus, usually caused by maternal-fetal blood group incompatibility and now rare in developed countries). In instances where the cortex is spared, children may have good cognitive function despite severe motor disability and speech impairment.

Ataxic Cerebral Palsy

Ataxic CP is the least common form of CP (<5%) and is characterized by hypotonia, trunk and gait ataxia, and limb ataxia (intention tremor, dysmetria). If speech is affected, dysarthria with a slow and scanning quality is typical. Brain imaging may demonstrate a cerebellar malformation or lesion, although it is often normal. Both dyskinetic and ataxic CP are associated with normal brain imaging in a significant proportion of children (approximately one-third and one-half, respectively). In these cases, it is important to consider further investigation for an underlying treatable or neurodegenerative condition (Table 137.3).

Management of Cerebral Palsy

Children with CP should be referred to a multidisciplinary specialty center and to an early intervention program for therapy services as soon as they are identified. Hearing and vision should both be assessed early. Interventions are directed toward: (1) spasticity management; (2) management of involuntary movements; and (3) improvement of strength, motor abilities, function, and self-care. Effective management requires ongoing regular follow-up as the child grows and develops so that realistic expectations and achievable goals can be set and periodically reevaluated.

Spasticity management aims to reduce hypertonia in order to maximize the child’s ability to gain muscle strength and range of movement through physical therapy, and to prevent long-term complications such as joint contractures and deformity. Functional goals depend on the severity of the child’s impairment. For example, the goal for a child with moderate spastic diparesis may be to achieve independent ambulation. In a child with severe spastic quadriplegia, seizures, and intellectual disability, the goal may be to improve comfort and ease the caregivers’ burden of care during daily activities such as dressing and bathing. The effect of spasticity on a child’s posture and motor function can change over time, often increasing noticeably during periods of rapid growth.

Only gold members can continue reading. Log In or Register to continue