Pediatric Neurologic Disorders

Generalized Seizures

Generalized seizures may be convulsive or nonconvulsive. A convulsive seizure may start focally and generalize secondarily. Convulsive status epilepticus is a true neurologic emergency defined as 5 minutes or more of continuous seizure activity (clinical or electroencephalographic) or recurrent seizure activity without return to baseline between seizures. Refractory status epilepticus is defined as status epilepticus that does not respond to first- and second-line antiepileptics. Super-refractory status epilepticus is defined as status epilepticus that persists 24 hours or more. Super-refractory status epilepticus is associated with a risk of mortality (3%) and long-term morbidity, including recurrent seizures and cognitive-behavioral impairment. The diagnosis of convulsive status epilepticus is usually obvious; however, the duration of the seizures is often underestimated because the intensity of the jerking tends to diminish with time. Status epilepticus occurs more frequently in children than in adults, particularly in those younger than 1 year. Medication changes, toxic ingestion, idiopathic epilepsy, metabolic derangements, and congenital abnormalities are common etiologies of pediatric seizures.

Nonconvulsive status epilepticus is marked by an altered mental status. Patients may demonstrate confusion, unresponsiveness, abnormal motor movements, twitches, lip smacking, automatisms, and sympathomimetic changes such as tachycardia, hypertension, and dilated pupils. An electroencephalogram (EEG) can confirm the diagnosis and should be obtained if nonconvulsive status is suspected. The most common type of generalized nonconvulsive seizure is absence seizures. Absence seizures are marked by a brief arrest of consciousness and movement, typically lasting 5 to 30 seconds; no postictal drowsiness occurs. It may be difficult to differentiate a brief complex partial seizure, in which a child may stare and not respond, from an absence seizure. Psychogenic nonepileptic seizures (PNES), caused by psychological factors, are events that look like generalized seizures but are not epileptic in nature. PNES are more common in patients with epilepsy, and patients with PNES are often later diagnosed with an epileptic seizure disorder.

Focal Onset

There are two types of partial (i.e., focal) seizures—complex and simple. In simple partial seizures, the patient experiences no change in mentation. In complex partial seizures, the patient experiences a change in level of awareness, and may exhibit bizarre behaviors, including staring, lip smacking, wandering, or picking at clothing. An important subcategory of focal seizures is composed of benign focal epilepsies of childhood, which are idiopathic in nature (i.e., they do not result from abnormalities in brain structure or injury to the brain). Benign focal epilepsies spontaneously resolve over time; benign childhood epilepsy with centrotemporal spikes (i.e., benign rolandic epilepsy) is most common and represents 10% to 20% of all childhood epilepsies.

The etiology of seizures can be divided into three categories—acute symptomatic, remote symptomatic, and idiopathic. Acute symptomatic seizures are provoked by an acute event such as fever. Remote symptomatic seizures are due to a preexisting or remote central nervous system (CNS) lesion such as cerebral palsy, neurocutaneous disorders, neurodegenerative disease, or a congenital brain malformation. Idiopathic seizures have no identifiable cause ( Table 169.3 ).

Fever is the most common cause of acute symptomatic seizures. A febrile seizure is defined as a seizure occurring in the presence of fever without CNS infection or other cause and occurs in up to 5% of children. A simple febrile seizure is generalized, lasts less than 15 minutes, and occurs in a neurologically and developmentally normal child between 6 months and 60 months of age. Complex febrile seizures are diagnosed when multiple seizures occur during the same illness, the seizures are longer than 15 minutes, or the seizures have a focal component. Febrile seizures typically occur early in the course of illness; higher temperature or reduction of fever with antipyretics does not reduce the risk of seizure. Meningitis should be considered in any patient with seizures and fever. However, a child whose mental status is normal before and after the seizure is very unlikely to have meningitis. We recommend considering a lumbar puncture in infants younger than 6 months presenting with febrile seizures, especially those with complex features or who have other risk factors for bacterial meningitis (e.g., underimmunized, comorbid disease, immunocompromised).

Electrolyte derangements including hypoglycemia, hyponatremia, and hypernatremia are other common causes of acute symptomatic seizures in children. Hypoglycemia resulting in seizure may be the first presentation of an infant with an underlying metabolic disease. Dehydration is the most common cause of hyper natremia, whereas hypo natremia may be secondary to overdilution of infant formula—a feeding history should be obtained in infants with abnormal serum sodium levels. Hypocalcemia and hypomagnesemia may lead to muscle spasms, paresthesias, hyperactive reflexes, weakness, tetany, or seizures. Hypocalcemic seizures are a common cause of neonatal seizures.

Posttraumatic seizures occur in as many as 15% of children after head injury. Impact seizures, occurring within 1 hour of a head trauma, are often not associated with significant injury or with the development of epilepsy and therefore trigger diagnostic imaging with CT. It may be difficult to distinguish impact seizures from those associated with intracranial injury; existing clinical decision rules and electronic decision support systems should determine need for intracranial imaging. Early posttraumatic seizures, occurring within the first week of injury, may arise from cerebral edema or intracranial hemorrhage or contusion.

Brain tumors and intracranial masses can present with seizures, depending on their location. However, infratentorial tumors, the most common location in the pediatric population, do not typically cause seizures. A seizure may be the presenting sign of stroke or vascular anomaly (discussed in more detail later in this chapter). Numerous drugs are known to cause seizures in children, especially in overdose. Cyclic antidepressants, cocaine and other stimulants, antihistamines, and isoniazid are the most common agents of drug-induced seizures. Seizures may occur during drug withdrawal from benzodiazepines or ethanol, usually within 48 hours of cessation.

Status Epilepticus

Status epilepticus is a true medical emergency. The patient should be positioned to maximize ventilation and prevent aspiration; attempts should be made to immobilize the cervical spine if trauma is suspected. Oxygen should be administered by nasal cannula or face mask with a bag valve mask for positive pressure if ventilation is inadequate. A large suction catheter should be available to suction oropharyngeal secretions. In younger patients, the tongue may obstruct the airway; a nasopharyngeal airway should be used to improve ventilation unless there is significant facial trauma. Oral pharyngeal airways may lead to vomiting when the seizure resolves and are often not utilized in treatment of seizures. If there is evidence of increased ICP, the head of the bed should be elevated. In a prolonged seizure, treatment with multiple medications or increased metabolic demand may lead to respiratory failure, necessitating intubation. We suggest that noninvasive measures are used to support ventilation in the initial phases of treatment before moving to intubation. If the decision is made to intubate, a sedative agent with antiepileptic activity should be selected (e.g., propofol, ketamine). In addition, a short-acting neuromuscular blocker (e.g., succinylcholine) is preferred to allow for monitoring of continued seizure activity as long as other contraindications to its use are not present.

Heart rate, blood pressure, respiratory rate, and pulse oximetry should be monitored and hyperthermia treated with antipyretics and cooling blankets. An IV line or, if an IV cannot be established, an IO line should be placed and blood samples sent for electrolyte values, glucose concentration (including rapid blood glucose test), calcium and magnesium levels, renal function tests, liver function tests, antiepileptic levels (when indicated), and CBC. Urine should be sent for toxicology. Metabolic abnormalities should be corrected.

Anticonvulsant treatment should begin as quickly as possible ( Fig. 169.3 ). Delays in the initiation of benzodiazepines of greater than 10 minutes is associated with higher frequency of death, longer seizure duration, and more complications. Benzodiazepines, particularly lorazepam and diazepam, are the initial drugs of choice in the treatment of status epilepticus; they diffuse quickly into the CNS, rapidly terminating seizure activity 70% of the time. Hypotension, respiratory depression, and impaired consciousness may occur after administration. Intranasal, buccal, or intramuscular routes may be used if IV or IO access cannot be obtained within the first 1 to 2 minutes of resuscitation and are preferable to rectal administration. Recommended doses for these non-IV preparations are shown in Fig. 169.3 .

A second dose of benzodiazepine should be administered only after 5 minutes of continued seizure activity following the first dose. If the seizure persists an additional 5 minutes after giving the second benzodiazepine dose, consider administering a third benzodiazepine dose and load with a second-line agent. The choices of second-line agents include levetiracetam, fosphenytoin, or valproic acid ( Fig. 169.3 ). There is limited evidence that one of these agents is preferred to the others. Recent controlled trials comparing phenytoin or phosphenytion to levetiracetam did not note a difference in the cessation of seizures. ^, One trial in Pakistan noted fewer adverse events and an improved efficacy for levetiracetam compared to phenytoin. Valproic acid is contraindicated in the presence of liver disease, thrombocytopenia, or possible metabolic disease. There is limited evidence consisting of case reports that ketamine may be effective in treating refractory status epilepticus compared to conventional anesthetics and other agents.

Fosphenytoin is a water-soluble phosphate ester of phenytoin that is rapidly converted in plasma to phenytoin. Unlike phenytoin, fosphenytoin can be administered intramuscularly and with common IV solutions and is substantially less cardio-toxic and less sclerosing to the vasculature. In addition, it can be given three times more rapidly than phenytoin. Fosphenytoin achieves plasma concentrations similar to those achieved for phenytoin. If seizures continue after loading with a second-line agent, another second-line agent can be administered. We recommend a propofol or a midazolam infusion as third-line agent to induce a coma. Other options include phenobarbital, pentobarbital, thiopental, or inhalant anesthetics. All have significant associated side effects and cause apnea, depressed consciousness, and hypotension; these side effects are more pronounced in the presence of benzodiazepines. Patients receiving these agents should receive continuous cardiorespiratory monitoring; staff and equipment should be readily available to support ventilation and advanced airway management.

Pediatric refractory status epilepticus is a high stakes and low frequency event and we recommend consultation with a neurologist when possible. Nonconvulsive status epilepticus is more difficult to recognize and often requires electroencephalography for diagnosis. Once the seizure has been effectively terminated, neuroimaging and lumbar puncture (LP) are often indicated to elucidate the cause of the seizure further.

Febrile Seizures

Children with simple febrile seizures do not require blood and urine testing other than as needed for the evaluation of fever source. An LP is not necessary in children older than 6 months with no signs of meningitis and no severe ill appearance before or after the seizure. If a child is less than 6 months or not fully immunized, an LP should be considered. Electroencephalography, neuroimaging, admission, or specialty consultation is not required after a first simple febrile seizure. Children who fully recover after a simple febrile seizure can almost always be sent home. Guidance for families should include high likelihood of recurrence (>33%), the small increased risk for the development of afebrile seizures (2% to 5% or double the baseline risk), fever control, and emergency measures for seizure. Extensive anticipatory guidance and reassurance should be provided to the family with close follow-up with their pediatrician.

Afebrile Seizures

For infants and children older than 6 months who have had a first-time afebrile seizure and have returned to baseline, laboratory testing should be pursued in a targeted manner, based on clinical and historical findings. A seizure in the setting of recent vomiting, diarrhea or starvation may warrant examination of serum chemistries for possible electrolyte abnormalities. A toxicology screening history should be performed to explore any medications in the home and laboratory testing considered. A lumbar puncture should be considered for patients who present with unprovoked seizures and persistent abnormal mental status, do not return to baseline, or show signs of meningitis. An outpatient EEG may be appropriate in well-appearing children who have returned to baseline.

Emergent neuroimaging should be performed in infants and children with new focal neurologic deficits, persistent altered mental status (including status epilepticus), recent trauma, persistent headache, or partial seizures. Children with generalized unprovoked seizures and normal examination findings on presentation do not necessarily require emergent imaging. A focal abnormality on follow-up EEG may indicate a need for neuroimaging, which can be done on an outpatient basis. Children with a history of epilepsy do not need neuroimaging unless there is a change in clinical status or marked change in seizure pattern.

If imaging is indicated in the acute period, CT or MRI may be used. Although MRI provides superior anatomic detail, sedation may be needed, impeding assessment of the patient’s mental status. When available, a rapid sequence MRI may provide sufficient information for the acute evaluation, with a full MRI planned for a later date. Often the initial imaging study of choice, CT provides rapid imaging and is highly sensitive for the detection of acute blood and fractures.

Neonatal Seizures

The common underlying causes of neonatal seizures in infants <1 month of age differ from those in older children and adults ( Box 169.1 ). In addition to congenital abnormalities, metabolic derangements, and birth-related injuries, neonatal seizures may be the only presenting sign of nonaccidental trauma. Diagnostic assessment of neonatal seizures is broad and includes metabolic testing (blood and urine), CSF analysis, and neuroimaging. Glucose, calcium, magnesium, and electrolyte levels (basic chemistry, including sodium, potassium, chloride, bicarbonate, blood urea nitrogen [BUN] and creatinine), and CBC should be obtained; lactic acid, ammonia, ketones, and pH determinations should be considered to assess for inborn errors of metabolism. Clinical assessment for meningitis is not reliable in young infants; thus, a LP should be performed and fluid sent for cell, protein, and glucose determinations, culture, and herpes simplex PCR assay. Head CT or MRI should also be performed when the neonate is stabilized. In the unstable neonate, a head ultrasound may be performed at the bedside to evaluate for a neurosurgical emergency until more definitive imaging can be obtained.

Empirical antibiotic coverage should be initiated if an LP is suggestive of bacterial meningitis. Antiviral therapy should be administered if there are clinical concerns for herpes encephalitis, including skin or mucosal findings, continued seizures with no other clear cause, or concerning maternal history; CSF red cells are a late and ominous finding. Electrolyte abnormalities, including hypoglycemia, hypomagnesemia, and hyponatremia, should be promptly corrected as described previously. If seizures are refractory to medical treatment, empirical treatment with pyridoxine, 15–30 mg/kg/day (not to exceed 500 mg/day), should be considered for the potential for a deficiency, and this dose can be repeated over the course of 30 minutes. This should be done with EEG monitoring, as clinical seizure detection in neonates is not reliable..

Phenobarbital is the usual drug of choice for neonatal seizures. However, there is increasing evidence of phenobarbital-induced neuronal apoptosis, even with a single dose, and evidence of memory and learning difficulties in rat models. Due to its potential harm, other potential first-line agents for the treatment of neonatal seizures are currently being investigated. If seizures continue, fosphenytoin may be loaded. Refractory seizures may be treated with a benzodiazepine infusion. Neonates with a first-time seizures should be admitted for continuous cardiorespiratory monitoring and evaluation by a neurologist.

Anticonvulsant Therapy at Discharge

The decision to start anticonvulsant prophylaxis should be done in consultation with a pediatric neurologist, balancing the risk of recurrent seizures against potential complications associated with long-term medication use. Two-thirds of children with a first unprovoked seizure never experience a recurrence. The risk for recurrence is increased with the presence of neuroimaging or electroencephalographic abnormalities, developmental delay, family history of epilepsy, remote symptomatic seizure, first seizure occurring during sleep, and Todd paralysis. If none of these risk factors are present, the 5-year recurrence risk is only 21%. There is no evidence that early treatment with anticonvulsant medications after a single seizure alters the risk of epilepsy, nor is there evidence to show that a single self-limited seizure causes neurologic sequelae. In light of these considerations, anticonvulsants are generally started after a second unprovoked seizure. The ED provider should only initiate a seizure medication upon discharge in consultation with a pediatric neurologist and is dictated by the seizure type and the side effect profile of the agent ( Table 169.5 ). Patients with acute symptomatic seizures associated with a risk factor for recurrence (e.g., cerebral hemorrhage, meningitis, or contusion) should be treated in the hospital with prophylactic anticonvulsants under the guidance of a neurologist; the decision to continue treatment should be made once the patient is stable.

Acute Headache

The acute headache is a common problem in children and adolescents and accompanies many infectious processes. In the absence of other signs of CNS involvement (e.g., nuchal rigidity, alteration in level of consciousness, or focal neurologic findings), headaches in febrile children usually do not constitute evidence of CNS infection; nonspecific viral illnesses or dehydration represent the most common diagnoses in children presenting to the ED with an acute headache.

Although far less common, arteriovenous malformations can be a trigger for a new severe headache. Intracranial arteriovenous malformations are structurally unstable and thus susceptible to spontaneous rupture. In children, the abrupt onset of a severe headache in the absence of trauma (especially when accompanied by focal neurologic findings) suggests an acute intracranial bleed, and a head CT should be performed. Localized acute headaches without focal neurologic findings may be due to sinusitis, otitis media, dental disorders, or traumatic head injury. Headache associated with trauma should be carefully investigated for the possibility of subdural or epidural hematomas, fractures, and leptomeningeal cysts (a “growing” skull fracture, usually in a child <3 years of age, with a history of recent trauma). Ophthalmologic problems, such as astigmatism, refractory errors, eye strain, and squint, are occasionally responsible for headaches in children.

Chronic Progressive Headache

Chronic progressive headaches in children often signify underlying pathology. The development of increased ICP can be caused by brain tumors, hydrocephalus, impaired venous drainage, brain abscess, or intracranial bleeding. Headache that awakens the child from sleep (related to increased CSF production in the later hours of sleep), is present on first awakening, or is associated with early morning emesis is a classic symptom of increased ICP and suggests an intracranial mass or hydrocephalus. In the setting of an abnormal intracranial entity, such as a mass or CSF obstruction, impaired venous outflow in the supine position leads to excess volume inside the skull, generating elevated pressure. The physical examination may show signs of increased ICP—vital sign changes, including hypertension, bradycardia, and irregular respirations (i.e., Cushing triad); papilledema; brisk reflexes; cranial nerve deficits; positive Babinski sign; or decreased level of consciousness—as well as focal symptoms related to the location of the lesion (e.g., hemiparesis, ataxia, visual field deficits).

Headaches are more likely to be the first symptom of a brain tumor in older children, but may be a later finding in younger children. Frequently, there are associated symptoms: nausea, vomiting; visual effects, problems with walking, weakness, loss of developmental milestones, changes in personality or school performance, or speech changes. As symptoms progress and evolve, the diagnosis of a brain tumor is often made after one or more clinical visits for headache. Loss of developmental milestones can be a potential sign of a brain tumor in infancy and childhood. Neurologic findings in children newly diagnosed with brain tumors may include papilledema, abnormal eye movements, ataxia, abnormal tendon reflexes, abnormalities on the visual examination, or less specific signs of increased ICP.

Clinical findings of pseudotumor cerebri (i.e., idiopathic intracranial hypertension or benign intracranial hypertension) are secondary to the increased ICP and include papilledema (with or without sixth cranial nerve palsy) and visual field deficits. Idiopathic intracranial hypertension (i.e., pseudotumor cerebri) is more common in females and obese individuals, and in younger children can be associated with medications (e.g., vitamin A, steroids, birth control pills, tetracycline). Neuroimaging is normal in idiopathic intracranial hypertension and the LP usually demonstrates elevated pressure, greater than 25 cm H ₂ O, and normal CSF protein and glucose levels. Neuroimaging should precede LP when increased ICP is suspected. We suggest any neuroimaging performed in the evaluation of idiopathic intracranial hypertension to include imaging of the venous sinuses, as cerebral sinovenous thrombosis (CSVT) can present similarly. Treatment is usually with diuretics, with or without an initial LP for therapeutic removal of CSF.

Brain abscess can result from meningitis, head trauma, chronic otitis media, sinusitis, or septic embolization in children with congenital heart disease. Focal neurologic signs, as well as fever and headache, may be present, but the patient may look surprisingly well. CT of the head without contrast enhancement is not sufficiently sensitive when an abscess is considered in the differential, but may be obtained; CT with and without contrast enhancement or MRI should be performed. CSF findings usually include a mild leukocytosis (10–200 leukocytes/mm ³ ), slightly elevated protein level, and normal glucose level. The CSF smear and culture do not usually reveal any organisms.

A subdural hematoma, epidural hematoma or intraparenchymal bleed are associated with head trauma. Headaches in these patients may evolve and progress over a relatively short time period. Symptoms include those associated with increased ICP, seizures, and focal neurologic deficits. The diagnosis is confirmed by neuroimaging.

Chronic progressive headache also can be a symptom of systemic diseases, such as hypertension, collagen vascular disease, hypothyroidism, Lyme disease, mononucleosis, or inborn errors of metabolism.

Migraine Headache

The diagnosis of migraine is based on symptoms of recurrent headaches separated by pain-free intervals. Migraine headaches are multifactorial in cause, with environmental and genetic contributions. The principal mechanism of migraine headaches is thought to involve a primary dysfunction of the brain in which a wave of spreading cortical neuronal depression is accompanied by vascular changes. Derangement of the trigemino-vascular reflex results in alterations of regional blood flow, and this neurovascular interaction is thought to contribute to neurogenic inflammation and the development of migraine headaches. Serotonin (5-hydroxytryptamine [5-HT]) may be a key mediator in this cascade of events, and serotonin agonists have been shown to relieve migraine pain.

Pediatric migraines may last from 2 to more than 72 hours and are more often bilateral than unilateral, which is more common in adults. Photophobia and phonophobia may be more difficult to assess in the young child or infant. Occipital headaches are rare and should raise clinical suspicion for a diagnosis other than migraine. Migraine headaches are classified primarily into migraine with and without an aura. Migraine without an aura, also known as common migraine, is the most frequent type of pediatric and adolescent migraine and includes the following criteria: more than 5 attacks that last 2 to 72 hours (untreated or unsuccessfully treated), accompanied by nausea, vomiting, photophobia or phonophobia, and including a minimum of 2 of the following criteria: unilateral or bilateral location, pulsing quality, moderate to severe intensity, and aggravated by routine physical activities.

Migraine with an aura, previously known as classic migraine, is diagnosed when at least two attacks fulfilling the diagnosis of migraine occur accompanied by a variety of sensory warning symptoms, such as flickering lights (scintillations), obscuration or loss of vision (scotoma), and tingling or numbness (paresthesias). The aura typically develops over 5 or more minutes and completely resolves within 60 minutes.

Migraine variants or atypical migraines are more common in children. Hemiplegic migraine is characterized by the sudden onset of hemiparesis or hemiplegia, along with headache in the contralateral hemisphere. Even though symptoms usually last for hours or even days, patients are rarely left with permanent deficits. These patients often receive imaging on initial presentation to exclude other diagnoses. Ophthalmoplegic migraine is characterized by severe unilateral eye pain and headache, followed by ipsilateral third nerve palsy of variable degree. Rarely, the fourth or sixth cranial nerve, rather than the third nerve, may be affected. Basilar artery migraine, also common in children, is manifested with a combination of visual symptoms (e.g., transient bilateral blindness, blurred vision) and visual hallucinations, vertigo, ataxia, loss of consciousness, and drop attacks. An acute confusional state can be associated with migraines and is characterized by changes in personality, orientation, or behavior. The so-called Alice in Wonderland syndrome includes perceptions of distortion in body images and shapes; objects appear much larger (macropsia) or smaller (micropsia) before, during, or after the headache.

Migraine variants are not uncommon and can be misdiagnosed. Abdominal migraine is characterized by recurrent abdominal pain, nausea, vomiting, and recurrent headaches. Benign paroxysmal vertigo of childhood (distinct from benign paroxysmal positional vertigo) is manifested as headache accompanied by the sudden onset of vertigo, pallor, and nystagmus. Paroxysmal torticollis is defined as recurrent episodes of head tilt associated with headache, nausea, and vomiting. Of note, this is a diagnosis of exclusion; children with a head tilt, vomiting, and headache should first be evaluated for a posterior fossa lesion. Ocular migraine is characterized by transient monocular visual blurring to blindness with bright flashes of light.

The incidence of seizures is higher in patients with migraine than in the general population. Although epilepsy and migraine headache are distinct clinical syndromes, they share several characteristics, such as aura, vertigo, nausea, pallor, loss of consciousness, drowsy postictal state, confusion, and transient focal neurologic deficits. Headache as the sole manifestation of a seizure is uncommon; however, headaches frequently follow tonic, tonic-clonic, and brief complex partial seizures. Bilateral frontal throbbing headaches may follow episodes of status epilepticus. Further neurologic evaluation, including electroencephalography, may occasionally be necessary to distinguish between these two syndromes.

Chronic Nonprogressive Headache

Chronic nonprogressive headache is commonly seen in the adolescent population. Included in this category are muscle contraction and conversion headaches. The International Headache Society classification of headaches refers to these types of headaches as tension headaches. This type of headache includes the following symptoms: bilateral or unilateral, nonthrobbing, pressing, or bandlike tightness of mild to moderate intensity, and the absence of nausea, vomiting, and aura. Tension headaches are further classified as episodic (10–15 episodes/month lasting 30 minutes to 7 days) or chronic (>15 episodes/month for more than 6 months).