Pediatric neurologic disorders present unique challenges. At a very young age, bone is highly plastic. Imbalance of muscle forces (spasticity and weakness) acting on bones and joints results in musculoskeletal complications such as excessive femoral anteversion, hip subluxation and dislocation, and flexion contractures of hips, knees, and ankles. Unlike adults, children’s brains are still developing, especially in the first 2 years of life, during which dendritization and synaptogenesis are highly active. Additionally, children may be learning new functional skills for the first time with the added challenge of compensating for an acquired neurologic condition.¹

Cerebral palsy (CP) is a heterogeneous condition with varied etiologies and degrees of severity. It is characterized by “disorders of the development of movement and posture, causing activity limitation, attributed to non-progressive disturbances in the developing fetal or infant brain”² before the age of 3 years.³ The motor disorders are often accompanied by disturbances of sensation, cognition, communication, perception, and/or behavior and/or by a seizure disorder.⁴

CP is classified by limb involvement—hemiplegia, diplegia, and quadriplegia—as well as motor disorder—spastic, dyskinetic (dystonia, chorea, and athetosis), ataxic, and mixed (a combination of the preceding). The Gross Motor Function Classification System (GMFCS) is commonly used (Table 58–1), and an expanded and revised age-specific version is now available.⁵

Epidemiology

The prevalence estimates of CP range from 1.5 to more than 4 per 1,000 live births, making it the most common motor disability in childhood.⁶ Approximately 80% is due to prenatal causes (i.e., prematurity, maternal infection, and low birth weight), 10% is due to perinatal events (asphyxia), and 10% is due to postnatal causes (trauma, meningitis).⁷

Diagnosis

CP is a clinical diagnosis based on a characteristic and consistent history and examination. The history should include a detailed birth history, especially gestational age, weight at birth, and any complications of pregnancy, labor, or delivery, including hypoxia, jaundice, and infections.⁷ Typically, children will have delays in developmental milestones, especially motor.⁷ Review of systems should include difficulty chewing and swallowing (sometimes the first symptoms to be identified), seizures, pain, bowel and bladder abnormalities, speech difficulties, and cognitive disorders.⁷ Hemorrhagic parenchymal infarction (HPI) in conjunction with examination should evaluate for progressive or degenerative features that would indicate a genetic or metabolic diagnosis instead.⁷ Family medical history should include asking about any neurologic, genetic, and metabolic disorders.

Physical examination should look for abnormal movement and/or increased or decreased muscle tone.⁷ Additionally, any stigmata or phenotype of a genetic condition, including the shape of the head, face characteristics, and limbs, should be sought. “Absent or abnormal fidgety movements (exaggerated amplitude, speed, or jerkiness) at age 3 months is 95% sensitive and 96% specific for the development of neurological deficits, and when coupled with findings from magnetic resonance imaging in preterm babies, is almost 100% accurate in predicting cerebral palsy.”⁷ By 18 months, motor impairments are usually evident, and the diagnosis of CP is usually made in the second to fourth year of life.⁷

Imaging should include a brain MRI to confirm the diagnosis, to tailor treatment, and a baseline in case of further deterioration. However, 20% of children with CP will have negative neuroimaging.⁸ Genetic and metabolic workup should be considered, especially if the history is inconsistent with CP (i.e., a loss of previously attained milestones or progressive deterioration).⁷

Management

In a review of interventions, the following were found to be effective⁹: (1) botulinum toxin, diazepam, and selective dorsal rhizotomy, (2) casting for ankle range of motion, (3) hip surveillance, (4) home therapy programs, constraint-induced therapy, bimanual training, context-focused and functional training, and occupational therapy following botulinum toxin injections, (5) fitness training, (6) bisphosphanates to improve bone density, (7) pressure care to reduce the occurrence of pressure ulcers, and (8) anticonvulsants for managing seizures.

Common oral medications include diazepam, which is fast acting and helpful for painful spasms at particular times of the day, and long-acting baclofen, which is better for continuous pain or to decreased constant increased tone interfering with function.⁷ Careful management should occur for feeding difficulties, drooling, mental health and intellectual impairment, seizures, communication difficulties, impaired vision and hearing, abnormal pain and touch sensation, sleep disturbance, and constipation.⁷ Special issues such as isolation, pain, and sexuality and gynecologic needs should not be overlooked. Equipment and orthoses are used to help improve and maintain function and quality of life.

Surgical interventions include orthopedic intervention for scoliosis, hip dysplasia, tendon contractures, and bony deformities often a result of spasticity and neurosurgical intervention with the intrathecal baclofen pump or selective dorsal rhizotomy.

Prognosis

Age of motor milestones can be used to help prognosticate whether a child will one day walk independently.¹⁰ The most common milestone includes the child being able to sit independently by age 2 years, which means that the child is more likely to be able to ambulate.^10,11 Ambulation, IQ, quality of speech, and hand function are predictive of employment status.⁴ Quality of life is not related to the degree of functional impairment.¹² Quality of life can be similar to that of subjects without CP when pain symptoms are controlled and patients are integrated into the community.⁷

Myelodysplasia

Myelodysplasia (also known as spina bifida) is a congenital malformation that develops when the neural plate fails to close during the first month of gestation and affects approximately 1,500 infants born annually.¹³ Spinal cord and vertebra formation begin at approximately 18 days’ gestation, and closure of the spinal canal begins at the cephalad end, proceeds caudally, and is complete by 35 days’ gestation. Most open neural tube defects occur between the twenty-second and twenty-sixth days of embryogenesis.¹⁴ Etiology appears to be multifactorial, with genetic, environmental, and nutritional factors having been implicated. For unknown reasons, spina bifida is more common in the eastern United States, and studies have been unable to conclusively identify a seasonal variation in prevalence. Inadequate intake of natural folate or its synthetic form, folic acid, before and during early pregnancy is associated with an increased risk of spina bifida. The current Recommended Daily Allowance (RDA) of 400 μg/day of folic acid has been established and recommended for women during pregnancy. An increased risk of spina bifida is associated with in utero exposure to valproic acid or carbamazepine alone or in combination with each other or other anticonvulsants. A genetic component to the disease appears to be present; if spinal bifida is present in one child, the chance of having a second child with the same condition is 2% to 5%. In addition, prevalence is increased in children born to mothers older than 30 years of age. Prepregnancy obesity, maternal diabetes, and increased body temperature in the early weeks of pregnancy are also associated with an increased risk of spina bifida.¹⁵

Spina bifida occulta is the mildest type of spina bifida in which there is a small gap in the spine but no opening or sac on the back. The spinal cord and the nerves are typically normal. A meningocele occurs when the meningeal sac extends beyond the confines of the vertebral canal but does not contain any neural elements. A lipomyelomeningocele is defined by the presence of fatty tissue and neural elements within the sac. The most common open neural tube defect is myelomeningocele, which is characterized by herniation of meningeal membranes and spinal cord tissue through a bony defect in the vertebral column, frequently in the lumbosacral regions¹⁴ (Fig. 58–1). Arnold-Chiari malformations are found in 85% of children with a myelomeningocele, and these children may require a ventriculoperitoneal shunt. Most children with myelomeningocele have a neurogenic bladder and bowel.

Maternal serum α-fetoprotein (AFP) and ultrasound are now routinely used to identify fetuses that have either spina bifida or anencephaly. Ultrasound is used to assess the severity of the malformation. When high levels of maternal serum AFP are found with normal ultrasound findings, an amniocentesis is recommended to check the level of AFP in amniotic fluid. High AFP can be seen in open ventral tube defects such as gastroschisis and omphalocele.¹⁵

Treatment of myelomeningocele is typically aimed at primary closure of the defect and preserving any viable neural structures. Traditionally, myelomeningocele closure is performed within the first 48 hours after delivery. Delay beyond 72 hours is associated with higher risk of meningitis, ventriculitis, and development of hydrocephalus-related complications. Prenatal repair before 26 weeks of gestation compared with postnatal repair has been found to improve neurologic outcome and decrease shunt dependence despite there being an increased risk of premature birth and maternal morbidity with these procedures.¹⁶ Long-term complications of myelomeningocele include lifelong paralysis, various degrees of mental retardation, bowel and bladder dysfunction, orthopedic disabilities, and hydrocephalus. Tethering can occur secondary to adhesions between the previously exposed neural elements and the surrounding tissues. In children with Arnold-Chiari II malformations, there may be complications related to the shunt.

Traumatic Spinal Cord Injuries

The incidence of spinal cord injury (SCI) in individuals 18 years of age and younger has been estimated to be 1.99 per 100,000 children and adolescents¹⁷ and is very rare in children younger than 5 years of age.¹⁸ The most common cause of SCI in children and adolescents is motor vehicle crashes, followed by violence and sports injuries. Unique etiologies of pediatric SCI include lap belt injuries, child abuse, delayed onset of neurologic deficits, and birth injuries. SCI may result from nontraumatic upper cervical spine instability related to syndromes such as Down’s syndrome or skeletal dysplasias, infections (tonsillopharyngitis), and inflammatory conditions (juvenile rheumatoid arthritis).^19,20 Infants and young children are more susceptible to upper cervical injuries (C1–3) and are more likely to suffer complete injuries in the cervical spine (80%) due to the large size of their head, immaturity of the spinal structures, and underdeveloped neck musculature.^20,21 Children younger than 10 years of age tend to be more susceptible to SCIs without radiographic abnormalities (SCIWORA) than adults due to increased mobility of the spine secondary to shallow occipital condyles, the horizontal orientation of the facet joints (30 degrees vs. 60–70 degrees in adults), small uncinate processes, immature uncovertebral joints, increased elasticity of the posterior joint capsules, and a cartilaginous junction between the vertebral bodies and their end plates.²²

By the age of 8 years, the level at which SCI occurs becomes similar to the adult population with fewer injuries at the C1–2 level and more at the C5–6 level as the fulcrum of flexion gradually shifts caudally, from C2–3 to C5–6.²³ Lap belt injuries most commonly affect children weighing less than 60 pounds because the lap belt rises above the pelvic brim.²⁴ The most common location for vertebral damage with lap belt injuries is between L2 and L4, although 23% to 30% of children with these injuries have SCIWORA.

Treatment and prophylaxis of medical issues after spinal cord injury in children are similar to those for adults, but certain medical issues in children with SCI are more unique in terms of incidence and management. Deep vein thrombosis prophylaxis, including anticoagulation and graduated elastic stockings, should be used for children older than 12 years of age. Graduated elastic stockings are preferred over elastic wraps due to the risk of unevenness of wrapping that can cause venous obstruction and increase the risk of deep vein thrombosis.²⁵ Low-molecular-weight heparin (LMWH) is ideal for prophylactic anticoagulation, and dosing must be closely monitored with anti-factor Xa levels because of variable rates of metabolism in children.²⁰ LMWH should not be used in the children younger than 13 years of age because of an increased risk for lower extremity and pelvic fractures.

Hypercalcemia is often seen after SCI, most commonly in adolescent and young-adult males, usually occurring in the first 3 months after injury. The typical presentation of hypercalcemia includes insidious onset of abdominal pain, nausea, vomiting, malaise, lethargy, polyuria, polydipsia, and dehydration. Patients may also exhibit behavioral changes or an acute psychosis. Management of hypercalcemia includes hydration with intravenous (IV) normal saline, administration of furosemide to facilitate renal excretion of calcium, or a single dose of IV pamidronate.²⁰ The effects of autonomic dysreflexia in children and adolescents with SCI are comparable to those in the adult SCI population. Blood pressure elevations of 20 to 40 mm Hg above baseline for each age group should be considered a sign of autonomic dysreflexia.²⁶ If high blood pressure is not responsive to conservative measures, nitropaste should be applied or nifedipine (0.25 mg/kg) administered for younger children and infants. Patients with recurrent autonomic dysreflexia may be managed with prazosin (25–150 μg/kg per day in divided doses every 6 hours) or terazosin (1–5 mg daily). Lesions at T6 or above interfere with central control of the thoracolumbar sympathetics and voluntary muscles of the lower body, resulting in a poikilothermic state. Infants and younger children are particularly vulnerable to environmental temperature extremes because of their relatively large surface area and their limited communication and cognitive abilities. In contrast, adolescents with SCI may be susceptible to hypothermia or hyperthermia because of their unpredictable behavior and judgment. Young people with SCI should be assessed for their risk of cardiovascular disorders, including obesity, sedentary lifestyle, hyperlipidemia, hypertension, smoking, and family history. Screening for lipid abnormalities should be pursued in children with a high-risk family history.²⁰ Neurogenic bladder is a serious problem for many with SCI. Similar to adults with SCI, the primary goals of neurogenic bladder management in children are to preserve renal function, prevent life-threatening complications, and promote continence. Clean intermittent urinary self-catheterization is the standard of care. Intermittent catheterization should be introduced at the age of 3 years, with the goal of obtaining complete independence by 5 to 7 years of age. Many of the management principles of neurogenic bowel are the same as for adults due to similar physiologic processes. Bowel programs can be successfully introduced around 2 to 4 years of age. Although conservative measures such as use of the gastrocolic reflex, gravity-aided postures, and suprapubic pressure (Credé’s maneuver) should be trialed first, more than 80% of children require the use of either oral, rectal, or combination medication regimens to manage neurogenic bowel and bladder.¹⁹ Heterotopic ossification is less prevalent in children, with an approximately 3% incidence rate, and is believed to show up later in children than in adults, occurring on average around 4 months after injury.²⁷ The pediatric SCI population is at an increased risk for developing a latex allergy, with an approximately 6% to 18% rate of occurrence. Risk factors for the development of latex allergy include age at exposure (with younger ages being at higher risk) and number of repeated exposures; therefore, all efforts should be made to prevent exposure.²⁰ Latex allergic reactions may manifest as localized or generalized urticaria, wheezing, angioedema, or anaphylaxis. Latex allergy should be suspected in individuals who have unexplained intraoperative allergic reactions or in individuals allergic to bananas, kiwi, avocados, or chestnuts.²⁸

Children who sustain their SCI before puberty experience a higher incidence of musculoskeletal complications, such as scoliosis and hip dislocation.²⁹ Pediatric SCIs pose unique management challenges because of the dynamic nature of cognitive and physical development in the growing child and the impact of the SCI on this complex process. Care for children and adolescents with SCI should be developmentally based, using appropriate strategies to facilitate adjustment and maximize independence across the spectrum of physical and emotional maturity levels. The goal of SCI rehabilitation for children and adolescents is to maximize function and independence and to prepare them for a successful transition to adulthood. Depending on age at injury, the acquisition of certain skills (e.g., bowel and bladder continence) may not be rehabilitation but rather habilitation because they may have never achieved this skill previously.¹⁹

Traumatic Brain Injury

Traumatic brain injury (TBI) can be defined as brain dysfunction caused by an external mechanical force. It results in a wide spectrum of signs and symptoms from mild temporary confusion to coma and death.

Epidemiology

The incidence of pediatric TBI is highest from birth to 4 years, with a second peak at 15 to 16 years of age. Falls are the most common cause of TBI in infants and preschoolers, abd sports activities are the main causes of injury in school-aged children and adolescent. Motorized vehicle accidents are the most common in 15- to 16-year age range. Severe TBIs in children are most often caused by motor vehicle accidents, except in infants, in whom assault is the most common cause. The majority of treated TBIs are mild (∼80%–90%).³⁰

Diagnosis and Classification

Diagnosis is made based on history of trauma and signs and symptoms of brain injury such as loss of consciousness, confusion, poor focus/memory, poor balance/coordination, weakness or numbness, nausea or vomiting, blurred vision, ringing in the ears, bad taste, slurred speech, photo- and phonophobia, fatigue, sleep changes, mood changes, headache, seizures, pupillary dilation, and clear fluids draining from nose or ear. Children should be observed closely for changes in eating, sleep, mood, attention, and interest in toys.³¹

Severity of TBI is indicated by postresuscitation children’s Glasgow Coma Score (GCS) and the duration of posttraumatic amnesia (PTA) using the Children’s Orientation and Amnesia Test (COAT).³² The definition of mild TBI for adults is often used for children and is defined by the World Health Organization (WHO) as confusion or disorientation; loss of consciousness (LOC) <30 minutes; PTA <24 hours; and transient neurologic abnormalities such as focal signs, seizure, or intracranial lesion not requiring surgery (GCS 13–15 after 30 minutes).³³ Moderate TBI indicates a GCS score of 9 to 12 and severe, a GCS score of greater than 9.³⁴

Severe TBIs can be divided into three stages: unconscious, PTA, and conscious. During the unconscious state, patients go through state, patients go through coma (eyes closed and (eyes closed and nonresponsive), vegetative (presence of a sleep-wake cycle, eyes open, some basic reflexes intact), and minimally conscious state (inconsistently able to follow one-step command). Once a patient is able to pass the COAT 2 days in a row, he or she has completed the PTA state and is able to retain new information and benefit most from a rehabilitation program.³⁵

Management

For acute TBI, the first step is to manage airway, breathing, and circulation (ABCs), followed by quick assessment for primary injury and life-threatening emergencies.³³ Early neuroimaging helps determine whether an extraventricular drain or decompressive craniectomy is required.³³ Intubation and pediatric intensive care unit (ICU) admission for close monitoring of hemodynamics and intracranial pressure (ICP) is recommended.³³ Sedatives and analgesics, usually an opioid and a benzodiazepine, are used to help with pain and anxiety and to synchronize respirations with the ventilator. Osmotic agents, preferably hypertonic saline 3%, are used to decrease ICP.³³ Seizures, both clinical and subclinical, are common, and antiseizure prophylactic medication should be considered in severe TBI.³³ Other monitoring includes avoidance of hyperglycemia and targeting arterial carbon dioxide level of 35 to 40 mm Hg. Patients should be positioned with their head at 30 degrees with a stable cervical spine collar.³³

Management for all TBIs, including very mild ones, must include educating families to look for symptoms and signs of sequelae of brain injury such as impairments in global cognition including attention, executive function, memory, and language that impede future learning and are associated with difficulties acquiring academic skills.³⁷ Late neurobehavioral deficits might include hyperactivity, inattention, aggressiveness, social withdrawal, apathy, and decreased motivation. There is some evidence that it may be beneficial to avoid a high degree of cognitive activity, but degree and duration of relative cognitive rest are unknown.³⁶ Strategies include transitional support into the classroom as well as extra time, monitoring, and assistance.³⁷ TBIs commonly result in transient or permanent hypopituitarism, so survivors should undergo serial screening for possible endocrine disturbances.³⁸

Prognosis

Overall, given a similar injury severity and type, most reports suggest that children have a better prognosis than adults, with lower likelihood of persistent vegetative state or death.¹⁰ When damage to the brain is focal, greater plasticity in children leads to an increased ability to recover. General factors that predict worse outcome in children include age under 4 years or adolescence (likely related mostly to mechanisms of injury in these ages), low GCS score, long PTA, prolonged coma, and secondary insults, including hypotension, hypoxia, and hypothermia. Overall recovery takes place within the first 6 months to 1 year, with a slowing of recovery and plateauing in the following years; nonetheless, children tend to have a longer recovery phase than adults. Most motor recovery occurs early on, with cognitive and intellectual recovery continuing into later years.

Brain tumors comprise approximately 20% of all childhood malignancies, second only to acute lymphoblastic leukemia in frequency. Pediatric brain tumors are different in location and behavior than adult tumors. The most common types of brain tumors in children are astrocytoma, medulloblastoma, and ependymoma.³⁹ Symptoms can include unsteady or imbalanced movement; vision loss, especially peripheral vision loss; double vision, particularly if associated with headache, gradual onset of speech difficulty, and loss of hearing, with or without dizziness; a steady headache that is worse in the morning; a persistent headache combined with nausea or vomiting; or a headache that includes weakness, numbness, double vision, memory loss, disorientation, and confusion. Treatment can vary based on types, grade, and location of tumors and is strongly influenced by the age and situation of the child. For most children, treatment starts with surgery. A biopsy following surgery will help to classify and grade the tumor. Additional treatment such as chemotherapy, conventional radiation therapy, and bone marrow transplantation, as well as rehabilitation therapy, is provided after surgical intervention.

Disabling sequelae occur often in a majority of patients with brain tumors. Complications after treatment include paralysis of limb(s), spasticity, muscle weakness, cognitive dysfunction, visual perception changes, and neurogenic bowel and bladder. While prognostic considerations factor into rehabilitation goals and expectations, the treatment team must offer cohesive support, facilitating hope, function, and quality of life. Inpatient rehabilitation, especially after surgical resection, has been shown to result in functional improvement and home-going rates on par with individuals with other neurologic conditions, such as stroke or TBI. Late effects after treatment such as cognitive dysfunction, infertility,⁴⁰ and poor adaptive functioning⁴¹ are not unique to children, but because children can live for many decades after treatment, education on the late effects of treatment has to be provided to parents and brain tumor survivors of all ages by the medical team. Proton therapy is believed to decrease late effects without altering survival in pediatric brain tumor patients. This hypothesis is currently being assessed in ongoing clinical trials with up-to-date proton devices.⁴²

Hypoxic-ischemic encephalopathy, known as perinatal asphyxia, is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia. Birth asphyxia causes 840,000 (23%) of all neonatal deaths worldwide.⁴³ Guidelines from the American Academy of Pediatrics (AAP) and the American College of Obstetrics and Gynecology (ACOG) for hypoxic-ischemic encephalopathy indicate that all the following must be present for the designation of perinatal asphyxia severe enough to result in acute neurologic injury: (1) profound metabolic or mixed acidemia (pH < 7) in an umbilical artery blood sample, if obtained, (2) persistence of an Apgar score of 0–3 for longer than 5 minutes, (3) neonatal neurologic sequelae (e.g., seizures, coma, hypotonia), and (4) multiple organ involvement (e.g., kidney, lungs, liver, heart, intestines).^44,45 Signs and symptoms of hypoxic-ischemic encephalopathy in acute stage are variable depending on its severity, including generalized hypotonia, diminished muscle stretch reflexes, absent or sluggish neonatal reflexes, irregular breathing that could require ventilatory support, and multiorgan dysfunction. Spasticity can be seen over time in infants with corticospinal tract damage caused by a hypoxic-ischemic insult. Hypoxic-ischemic encephalopathy is often reported to be the most frequent cause of neonatal seizures, with most seizures occurring within 12 to 24 hours after birth. Following initial resuscitation and stabilization, treatment of hypoxic-ischemic encephalopathy includes therapeutic hypothermia as well as supportive measures focusing on adequate ventilation and perfusion, careful fluid management, avoidance of hypoglycemia and hyperglycemia, and treatment of seizures. Intervention strategies aim to avoid any further brain injury in these infants. Given the current state of knowledge, initiation of treatment within the therapeutic window (before 6 hours of life) and duration of hypothermia for 72 hours with slow rewarming is essential to provide the best care to critically ill newborn infants with neonatal encephalopathy.⁴⁶ Many children who survive birth asphyxia develop problems such as CP, mental retardation, learning difficulties, and other disabilities.⁴⁷ Therefore, it is important that rehabilitation therapy starts while they are in the neonatal ICU. After they become medically stable, they will be discharged to home or rehabilitation center based on their disabilities and will be assessed by an early intervention program team to receive ongoing therapy services.

Shaken baby syndrome is a nonaccidental head trauma that occurs in infants as a result of the brain pushing against the skull due to severe acceleration-deceleration forces and remains the most common cause of death in children who are victims of nonaccidental trauma. Shaken baby syndrome usually occurs during the first year of life.

The diagnosis of shaken baby syndrome is often missed because no history of head trauma is provided, and the signs and symptoms the child displays may be nonspecific, such as vomiting, poor feeding, irritability, or lethargy. MRI and ocular examinations are used to determine the extent of mental and visual damage, and β-amyloid precursor protein immunohistochemical staining is used to detect axonal injuries.

Symptoms of shaken baby syndrome include subdural, subarachnoid, and retinal hemorrhages. Therefore, it is important to maintain a wide differential diagnosis, including birth trauma, coagulopathy, congenital vascular malformations, spontaneous subdural hemorrhage, and metabolic deficiencies such as glutaric aciduria type I. Surgeries, such as subdural hemorrhage evacuation surgery and the burr hole craniotomy, are used to treat shaken baby syndrome, but the prognosis is poor in many cases. Because of the severity of shaken baby syndrome and its traumatic and sometimes fatal effects, it is important to educate new parents, nurses, and doctors on the syndrome in order to prevent incidents.^48,49

Peripheral neuropathy, a disorder of the peripheral nerves, can be caused by many systemic illnesses, drugs, and toxins. It is typically characterized by weakness, sensory loss (numbness), and/or positive sensory symptoms such as paresthesia, pain, or burning sensations.

Hereditary Motor Sensory Neuropathies

Hereditary motor sensory neuropathy (HMSNs), also known as Charcot-Marie-Tooth (CMT) disease, is the most common inherited neuropathy, with an estimated prevalence of 1 in 2,500.⁵⁰ CMT disease is a disorder that most commonly causes progressive distal-to-proximal weakness with associated atrophy and sensory deficits, usually affecting the feet and legs at onset. CMT disease was originally classified by Dyck as HMSN I–VII (Table 58–2). However, due to rapidly developing genetic discoveries, a growing number of genetic subtypes of CMT disease has been found, and Dyck’s classification is not able to describe the genetic heterogeneity within each of the categories.⁵¹ CMT disease type I is the most commonly diagnosed form, representing approximately 50% to 80% of all CMT disease. An overview of single-gene causes of CMT disease based on inheritance patterns, pathology, and genetics has been simplified.⁵²

The most characteristic clinical signs in CMT disease are distal limb weakness and muscle atrophy. The neuropathy is length dependent, meaning that the longest nerves in the body are affected first and most severely. Therefore, the lower extremities are usually affected earlier than the upper extremities in the course of disease progression. In toddlers, the earliest clinical signs are delayed motor development and toe walking, along with tripping or falling. In older children, slow running, ankle injuries, and clumsiness in sport activities are red flags. The most typical foot abnormalities are high arch (pes cavus) and hammer toes (claw feet), but flat foot (pes planus) may be a rare finding. Hand weakness may not present until the child is older and has difficulty dressing, tying shoes, or writing at school. Dejerine-Sottas disease, the rare, severe infantile CMT disease, presents with floppy-infant features such as nonspecific clinical signs of generalized hypotonia, hip dysplasia, decreased sucking effort, and, in more severe cases, breathing problems. After the neonatal period, most infants survive and eventually improve to achieve motor skills with variable delay.⁵³

The diagnosis of HMSN is made through thorough history taking, assessment of clinical symptoms and signs, rapidity of onset, and diagnostic studies including electrodiagnosis and genetic studies. Electrodiagnostic testing, including electromyogram and nerve conduction studies (EMG/NCV), is the first test of choice for confirming and identifying various forms of neuropathy and for differentiating between demyelinating and axonal types. If the EMG/NCV test confirms a demyelinating CMT disease, a genetic test for PMP22 gene duplication determination should be performed as the next most informative and cost-effective test, and it is positive in 70% of patients. However, a negative genetic test does not exclude a CMT disease diagnosis, especially in axonal forms.⁵³

There is no curative treatment available for CMT disease at this time. Tricyclic antidepressants, gabapentin, and anticonvulsants can be used to address neuropathic pain. Low-intensity exercise and stretching exercises seem to have a beneficial impact. Orthopedic surgical interventions may be required for progressive foot deformity and can include tendon lengthening and/or transfer, osteotomy, and arthrodesis. Ankle-foot orthoses have been used to improve ankle instability and walking balance. Genetics-based therapies, such as molecules that can correct nonsense mutations or facilitate gene expression regulations, hold promise in specific therapies for the future of CMT disease treatment.⁵³

Brachial Plexopathies

Brachial plexopathies occur in two different age groups. Neonatal brachial plexus palsy (NBPP) is a recognized complication of childbirth, with an incidence between 0.04% and 0.4% of live births.⁵⁴ The next peak in the incidence of brachial plexopathies occurs in younger (usually male) adults, and it is often caused by motor vehicle accidents or penetrating wounds. Therefore, this chapter focuses on NBPP.

NBPP is defined as an injury to any nerve root of the brachial plexus during a difficult delivery. It is mostly due to unpredictable risk factors, such as shoulder dystocia or macrosomia with a birth weight greater than 4 kg. Both diagnosis and assessment are based on clinical examination, such as asymmetrical active movements between both arms and flaccidity of the involved arm, and may be seen with the classic Horner’s syndrome triad of ptosis, myosis, and enophthalmia. Infants with Erb’s palsy (paralysis of the upper nerve roots with C5, C6, ±C7 nerve root involvement) demonstrate a characteristic spontaneous position: shoulder in adduction and internal rotation, elbow in extension, forearm in pronation, and wrist in extension. If the lesion extends to the C7 root, the wrist will be in flexion with an ulnar inclination, and the fingers retain their physiologic tonicity in flexion. Erb’s palsy is the most common postganglionic lesion, occurring in more than 75% of NBPP patients. Klumpke’s palsy, which causes distal paralysis, presents with the wrist and hand inert, whereas the elbow and shoulder retain normal function. This is rare and accounts for less than 2% of cases. Infants with total paralysis, in which the upper limb is completely inert and dangling, account for approximately 20% of cases. This often indicates a radicular avulsion of the distal roots, which worsens the prognosis. Infants may have signs and symptoms of the sympathetic nervous system such as vasomotor problems causing skin blotches, local coldness, and sweating and Horner’s syndrome. Further investigations should include shoulder x-ray to rule out scapular or humeral fracture and a chest x-ray to rule out phrenic paralysis.⁵⁵

Electromyography (EMG) is difficult to interpret in the newborn, and use of this study has been controversial.⁵⁶ If surgery is indicated, an MRI of the cervical spine should be performed to identify the presence of a preganglion tear. Prognosis depends on the level of the injury (pre- or postganglion), size and severity of the postganglion tears, speed of recovery, and quality of initial management. Although spontaneous recovery is frequent (75%–95%), some children suffer various degrees of sequelae (20%–30%) from mild motor involvement to complete loss of function of the affected upper limb. Treatment is first conservative, and infants with NBPP who do not recover during the first 2 months should be managed with a multidisciplinary team. In general, nerve surgery is recommended at 3 months of age for infants with total paralysis and at 5 to 6 months of age for infants with partial paralysis who have had no biceps recovery. However, some aspects, such as indication and timing of nerve repair, continue to be debated.⁵⁵

Rehabilitation management includes the development of treatment plans that address both short- and long-term goals. Therapy evaluation and treatment can and should begin as early as day 1 of life, particularly in cases where the infant is otherwise medically stable. The most important goal of early therapy for NBPP patients is maintenance of soft tissue and joint flexibility. Passive range-of-motion exercises are critical and must be taught to the parents/caregivers to be performed routinely at home. Motor training to stimulate activity in denervated muscles should begin as early as possible and continue for as long as nerve recovery is still occurring (potentially for years). This will help to prevent or minimize soft tissue contractures and to minimize ineffective substitution movements. Botulinum toxins have been applied to agonist and antagonist muscles to facilitate movement and improve range of motion by relaxing muscles temporarily as an adjunctive tool.⁵⁷

Acquired/Toxic Neuropathies

Many chemicals, toxins, and drugs can cause peripheral neuropathy. Excessive vitamin intake can also be neurotoxic. Chronic lead poisoning causes a motor neuropathy known as “mononeuritis multiplex,” which selectively involves large nerves such as the common peroneal, radial, and median nerves.⁵⁸ Arsenic poisoning produces painful burning paresthesias and motor polyneuropathy.⁵⁹ The most frequent cause of toxic neuropathies in children is prescribed medications. Polyneuropathies may develop as a complication from the use of antimetabolic and immunosuppressive drugs such as vincristine, cisplatin, and packlitaxel, used as chemotherapy for neoplasm and immunologic disorders such as juvenile idiopathic arthritis. This neuropathy results from axonal degeneration rather than primary demyelination.⁶⁰ Biologic neurotoxins associated with diptheria, Lyme diseases, West Nile virus disease, leprosy, herpes viruses (Bell’s palsy), and rabies also produce peripheral nerve– or anterior horn cell–induced weakness or paralysis.⁶¹

Entrapment Neuropathies

Entrapment neuropathies are rare complications in children.⁶² The ulnar nerve is at increased risk of entrapment because of its curvature around the elbow joint. Any pathologic condition that alters the normal anatomy of the elbow joint can lead to stretching or irritation of the nerve. Ulnar neuropathies are the most common upper extremity mononeuropathies seen in children and are most commonly found at the cubital tunnel.⁶³ Etiologies include, but are not limited to, acute trauma, compression from compartment syndrome, baseball throwing injuries, and insulin-dependent diabetes mellitus. Tardy ulnar nerve palsy is a chronic clinical condition characterized by delayed-onset ulnar neuropathy. It typically occurs as a consequence of nonunion of the lateral condyle, resulting in cubitus valgus deformity, which causes the ulnar nerve palsy.⁶⁴ Radial nerve neuropathies are very rare. While carpal tunnel syndrome (CTS) is rare in children, those with mucopolysaccharidosis types I, II, and III and mucolipidosis are at increased risk.⁶⁵

The most common entrapment in the lower extremities is peroneal mononeuropathy occurring at the fibular head with a physical presentation of unilateral foot drop. Common etiologies include compression from a short leg cast, compression from prolonged surgical positioning, and trauma. Sciatic mononeuropathies, while uncommon, may be caused by direct trauma and iatrogenic mechanisms and can rarely be caused by tumor and vascular and compression injuries.⁶⁶

Guillain-Barré Syndrome

Guillaine-Barré syndrome (GBS) is the most common cause of ascending flaccid paralysis in the United States with an annual incidence of 1.2 to 3 per 100,000 inhabitants.⁶⁷ It is caused by acute inflammatory demyelinating polyradiculopathy (AIDP) and results in weakness and diminished or absent muscle stretch reflexes. GBS is typically a postinfectious disorder, as shown by the rapidly progressive monophasic disease course that occurs shortly, usually less than 1 month, after infection and typically occurs without relapse. Infections associated with GBS are Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, influenza A virus, Mycoplasma pneumoniae, and Haemophilus influenzae. Cases of GBS have also been reported shortly after vaccination with Semple rabies vaccine and various types of influenza A virus vaccine. Typically, vaccinations are not contraindicated for patients with prior episodes of GBS, unless one occurred in the past 3 months or they had vaccination-related GBS. However, risk and benefit might be discussed on a case-by-case basis.⁶⁸ There are several well-recognized variants of GBS, including acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Miller-Fisher syndrome. Miller-Fisher syndrome is characterized by the triad of ophthalmoplegia, ataxia, and areflexia.⁶⁹

Clinically, GBS causes rapid bilateral progressive ascending weakness with complaints of finger dysesthesias and proximal muscle weakness of the lower extremities.⁶⁹ It typically presents 2 to 4 weeks following a relatively benign respiratory or gastrointestinal illness. Most patients will reach the nadir within 2 weeks, but in rare cases progression can last up to 6 weeks after onset and is then considered subacute GBS. During the progressive phase, 20% to 30% of patients develop respiratory failure and need ventilation in an ICU. GBS weakness can involve the cranial nerves, especially CN VII involvement with facial droop. Reflexes can be normal initially, especially in pure motor and axonal forms of the disorder or, in a few cases, even be hyperreflexic.⁷⁰ However, most patients have, or develop, reduced tendon reflexes in the affected limbs.⁶⁸ There could be autonomic changes associated with GBS such as tachycardia, bradycardia, facial flushing, orthostatic hypotension, and urinary retention.

GBS is generally diagnosed on clinical grounds. A classic laboratory finding for GBS is cytoalbuminologic dissociation—the combination of a normal cell count and increased protein level. However, normal protein level (especially when determined in the first week after onset of disease) does not make the diagnosis unlikely or even exclude GBS.⁷¹ Additionally, 15% of patients with the disease have a mild increase in cerebrospinal fluid (CSF) cell count (5–50 cells/µL).⁷²

Nerve conduction studies show delayed conduction velocity, prolonged distal latencies, prolongation of F-waves, and decreased recruitment on EMG. MRI is sensitive and can show spinal nerve root enhancement with gadolinium, but this finding is nonspecific for diagnosis. However, an MRI finding of selective anterior nerve root enhancement is strongly suggestive of GBS.⁶⁹

Early initiation of intravenous immunoglobulin (IVIG) or plasma exchange is crucial and has been proven to be beneficial, especially in patients with rapidly progressive weakness.⁶⁸ Subcutaneous unfractionated or low-molecular-weight heparin (LMWH) is often used in the treatment of immobile patients to prevent lower extremity deep venous thrombosis (DVT) and consequent pulmonary embolism. For the patients with respiratory muscle involvement, negative inspiratory force (NIF) must be measured. Normal NIF is usually greater than 60 cm H₂O, but if the NIF is dropping or if it is near 20 cm H₂O, respiratory support needs to be available. After acute medical management, intense rehabilitation therapy is beneficial in helping patients with GBS to regain their baseline functional status. Approximately 80% patients with GBS walk independently at 6 months after onset, and about 60% of patients attain full recovery of motor strength by 1 year after onset. For a small subset of patients, approximately 5% to 10%, recovery is prolonged, with several months of ventilator dependency and a very delayed and incomplete recovery. Some factors that may indicate a poor prognosis include a preceding gastrointestinal infection or diarrheal illness, older age (57 years or older), poor upper extremity muscle strength, acute hospital stay of longer than 11 days, ICU requirement, need for mechanical ventilation, Medical Research Council (MRC) score below 40, and requiring discharge to a rehabilitation facility. Mean compound muscle action potential (CMAP) amplitudes of less than 20% of the lower limit of normal and the presence of inexcitable nerves on initial electrophysiologic studies are other predictors of poorer functional outcomes. The follow-up electrophysiologic study after 1 month from onset showed that persistence of a low mean CMAP has an even higher sensitivity and specificity than do initial tests showing low amplitude.⁶⁹ High CSF levels of molecular weight neurofilament (NfH) protein, an axonal protein, are prognostic indicators in GBS.⁷³ Increased CSF levels of neuron-specific enolase and S-100b protein and a prolonged increase in immunoglobulin M (IgM) anti-GM1 are also associated with longer duration of illness.⁶⁷

Myopathies are neuromuscular disorders in which the primary symptom is muscle weakness due to muscle fiber dysfunction. Other symptoms of myopathies can include muscle cramps, stiffness, and spasm. Myopathies can be inherited (e.g., muscular dystrophies) or acquired (e.g., common muscle cramps). Myopathies have several classifications: congenital myopathies, muscular dystrophies, mitochondrial myopathies, glycogen storage diseases of muscle, dermatomyositis, myositis ossificans, familial periodic paralysis, polymyositis, inclusion-body myositis, and related myopathies including neuromyotonia and common muscle cramps, stiffness, and tetany. Muscular dystrophy is a group of inherited diseases that is characterized by muscle weakness and atrophy with and without nerve damages. The most well-known of the muscular dystrophies is Duchenne’s muscular dystrophy (DMD), followed by Becker’s muscular dystrophy (BMD).

Treatment for myopathy depends on the disease or condition and specific causes. Supportive and symptomatic treatment may be the only treatment available or necessary for some disorders. Management for these disorders often includes drug therapy (e.g., immunosuppressives), physical therapy, bracing to support weakened muscles, and surgery. Clinicians should counsel patients with muscular dystrophy on parameters for physical exercise and exertion. Aerobic exercise combined with a supervised submaximal strength training program is probably safe. Gentle, low-impact aerobic exercise, such as swimming or stationary bicycling, can improve cardiovascular performance, increase muscle efficiency, and lessen fatigue.