Etiology and Pathogenesis

Common to the pathophysiology of all seizures is the hypersynchrony of neuronal discharges. The inciting cause varies and may include metabolic, anatomic, infectious, and primary neurologic processes (see Chapter 74). Uncovering the cause of SE is essential because it guides subsequent evaluation and management of a patient in SE.

Clinical Presentation

Differential Diagnosis

There are other paroxysmal events that can mimic seizures in children that must be considered in the differential diagnosis. Breath-holding spells occur in children 6 months to 4 years of age and consist of a period of crying resulting from an inciting event, such as trauma, followed by breath holding and ensuing pallor or cyanosis. The child becomes rigid and may have twitching movements but quickly returns to a full level of alertness. Syncope, a brief loss of consciousness and muscle tone, can be differentiated from seizure by history and physical examination (see Chapter 48). Sleep disorders, such as night terrors, benign myoclonus, and sleep paralysis, can mimic seizures.

Evaluation and Management

The initial management of a child with SE includes assessment and support of the patient’s airway, breathing, and circulation (ABCs). The administration of supplemental oxygen is recommended, and intravenous (IV) access should be established. Initial laboratory testing should include basic electrolytes and a bedside glucose test. Children in SE should be protected from trauma, although objects should not be placed in the patient’s mouth to prevent tongue biting.

Children who arrive in the emergency department actively convulsing should be assumed to be in SE and given pharmacologic agents to stop the seizure. If hypoglycemia is present, 0.5 g/kg of IV dextrose should be given using the “rule of 50s” (multiply the volume of fluid in mL/kg by the concentration of dextrose to equal 50, e.g., 2 mL/kg of 25% dextrose in water, 5 mL/kg of 10% dextrose in water). Other electrolyte abnormalities should be addressed as well. Hyponatremia, hypocalcemia, and hypomagnesemia can all result in seizure. Patients with hyponatremia (usually <125 mEq/L) are treated with 3 to 5 mL/kg of 3% saline IV, hypocalcemia with 0.3 mL/kg of 10% calcium gluconate IV, and hypomagnesemia with 50 mg/kg of magnesium sulfate IV.

Benzodiazepines are the first-line anticonvulsant medications for treating children with SE (Table 10-1). IV lorazepam is usually preferred, but if IV access is not available, midazolam can be given via the buccal or intramuscular route or diazepam can be administered rectally. Although these agents have similarly rapid onsets of action, lorazepam lasts much longer than other benzodiazepines (≤12-24 hours). As a result, one must be mindful to administer another agent for long-term seizure control when using other benzodiazepines as a first-line agent. If the patient does not have seizure remittance after benzodiazepine administration, phenytoin (or fosphenytoin) is widely considered the next anticonvulsant agents to use. Although phenobarbital has been used as a second-line agent in SE, phenytoin is preferred because by acting on voltage-gated sodium channels, its mechanism of action is different than lorazepam. Lorazepam and phenobarbital, on the other hand, are both GABA (γ-aminobutyric acid) receptor agonists. Phenobarbital and some newer anticonvulsant medications, such as levetiracetam, are considered third-line agents for SE. Consultation with a pediatric neurologist and/or pediatric intensivist are warranted when treatment beyond benzodiazepines is used.

Table 10-1 Suggested Treatment Algorithm for Status Epilepticus

Etiology and Pathogenesis

ALOC occurs when there is dysfunction of the reticular activating system in the brainstem and pons, which is responsible for wakefulness, or the cerebral hemispheres, which are responsible for awareness. For these structures to function properly, the nervous system needs to be free from abnormal irritation, body temperature needs to be in the normal range, adequate blood flow needs to exist to these areas to bring vital energy-producing substrates, and the body needs to be free of metabolic waste products or toxins. Whenever there is an alteration in one of these factors, ALOC ensues. There are myriad causes for the aforementioned alterations in consciousness. The mnemonic VITAMINS outlines the most prevalent causes (Table 10-2).

Table 10-2 Causes of Altered Level of Consciousness (“VITAMINS”)

ALOC, altered level of consciousness; AVM, arteriovenous malformation; DKA, diabetic ketoacidosis; ICP, intracranial pressure; TCA, tricyclic antidepressant.

Evaluation and Management

The initial management of ALOC includes assessment and support of the patient’s ABCs. This is followed by a detailed history that may help narrow the differential diagnosis. Questions should focus on the patient’s past medical history (e.g., diabetes mellitus, epilepsy) as well as the circumstances surrounding the onset of symptoms (e.g., head trauma, possible toxin ingestion, presence of fever). Specific questions about physical signs and symptoms such as headache, irritability, vomiting, gait disturbances, and behavioral abnormalities should also be asked.

Subsequent examination of the patient begins with a global neurologic assessment using the AVPU scale or the Glasgow Coma Scale and an evaluation of vital signs, including core temperature. Pupillary response can provide important clues to the underlying cause of ALOC. A unilateral dilated pupil can indicate mass effect and increased ICP, and bilateral enlarged pupils might represent severe global intracranial dysfunction or an ingestion of sympathomimetic or anticholinergic substances. Pinpoint bilateral pupils may result from ingestion of opiates. The patient should next be examined for signs of head trauma such as scalp hematoma, retinal hemorrhage, hemotympanum, cerebrospinal fluid (CSF) otorrhea or rhinorrhea, postauricular hematoma, periorbital hematoma, and other visible signs of head injury. Evaluation for infection, especially in the setting of fever, should include testing for meningeal irritation using Kernig’s (resistance to bent knee extension with the hip in 90 degrees flexion) and Brudzinski’s (involuntary knee and hip flexion with passive neck flexion) signs (Figure 10-2). Other stigmata of infectious causes for ALOC include petechiae or purpura found in patients with meningococcal sepsis.

Figure 10-2 Kernig’s and Brudzinski’s signs.

Laboratory evaluation of patients with ALOC should be determined based on the most likely causes. A bedside glucose test along with basic electrolytes, blood urea nitrogen, and creatinine can uncover correctable metabolic derangements. Blood gas analysis, complete blood count with differential, and toxicologic screening of blood and urine may also be helpful. An empiric trial of the opioid antagonist naloxone should be considered in patients with unexplained ALOC, especially with associated respiratory depression and miosis, and in toddler or adolescent patients because of their higher risk of poisoning (see Chapter 9). Brain imaging is helpful in revealing possible hemorrhage, malignancy, abscess, hematoma, cerebral edema, and hydrocephalus. A high index of suspicion for nonaccidental trauma must be maintained, especially in infants with ALOC, even in the absence of physical signs of injury. If fever or other signs of CNS infection are present, lumbar puncture is warranted, and empiric antibiotic therapy with a third-generation cephalosporin (e.g., cefotaxime) should be started, with other antibiotics, such as ampicillin or vancomycin, added if indicated by age and clinical situation. Electroencephalography (EEG) may also be necessary to evaluate for nonconvulsive seizures in patients with ALOC. Ultimately, definitive treatment depends on the results of the diagnostic evaluation.

Etiology and Pathogenesis

Elevated ICP in children is most often a complication of traumatic brain injury. Other common causes include hydrocephalus, brain tumors, and intracranial infections. Prompt recognition and treatment of increased ICP is vital to avoid morbidity and mortality. The intracranial compartment is a fixed internal volume composed of brain parenchyma (80%), CSF (10%), and blood (10%) protected by the skull. ICP is a function of the volume and compliance of each component. The Monro-Kellie doctrine states that because the intracranial compartment is a fixed space, an increase in volume of one compartment requires displacement of other structures, an increase in ICP, or both. Cerebral blood flow must be maintained to provide oxygen and nutrients for metabolic activity. Cerebral perfusion pressure (CPP) is used clinically to define the adequacy of cerebral perfusion. It is defined as:

Normal CPP in children can be estimated to be around 50 to 60 mm Hg based on normal ICP of less than 20 mm Hg and mean arterial pressure (MAP) greater than 70 to 80 mm Hg. Inadequate CPP caused by systemic hypotension or elevated ICP may result in ischemic brain injury. Therefore, management of increased ICP must take into account the ultimate goal of maintaining CPP.

Clinical Manifestations

Children with increased ICP may present with headache, decreased consciousness secondary to increased pressure in the midbrain reticular formation, or vomiting. Headache is an early symptom and is typically characterized by a progressive increase in frequency and severity, nocturnal awakening, and worsening with Valsalva maneuvers (cough, defecation, micturition). Infants may present with a bulging fontanelle, poor feeding, lethargy, and flat affect. Funduscopic examination may reveal papilledema, but the absence of this finding does not rule out increased ICP, especially if it has developed acutely (Figure 10-3). The presence of retinal hemorrhages should raise suspicion for nonaccidental head trauma (e.g., shaken baby syndrome; see Chapter 12). Infants may have a “sun-setting” appearance of their eyes, split sutures, or a bulging fontanelle. Dilated pupils (unilateral or bilateral) may be present along with cranial nerve palsies (most commonly the third and sixth nerves). Such cranial nerve palsies can cause double vision and head tilt as the patient tries to correct for the visual discrepancy. Hemiparesis, hyperreflexia, and hypertonia are late signs of increased ICP. Development of Cushing’s triad (bradycardia, systemic hypertension, and irregular respirations) is a late indication of impending cerebral herniation, with bradycardia being the earliest feature.

Figure 10-3 Signs of increased intracranial pressure.

Evaluation and Management

The initial management of a child with suspected increased ICP includes assessment and support of the patient’s ABCs. Endotracheal intubation should be considered if there is concern for loss of airway protective reflexes, severe hypoxia or hypoventilation, or acute cerebral herniation. Hyperventilation (goal PaCO₂ of 30-35 mm Hg), which leads to cerebral vasoconstriction and decreased cerebral blood flow, should be performed to acutely decrease ICP in the case of acute herniation. However, overly aggressive hyperventilation may lead to ischemic injury. Especially in cases of head injury and multisystem trauma, MAP must be supported to preserve CPP. After initial hemodynamic stabilization has been achieved, the patient should undergo computed tomography (CT) of the brain, which may reveal an underlying cause for the increased ICP. It is important to remember that ICP can be elevated in the setting of a normal initial CT. In one study, 33% of patients with initially normal head CTs developed CT scan abnormalities within the first few days after closed head injury. Thus, close monitoring in an intensive care unit is necessary for patients with suspected increased ICP.

Pharmacologic therapy may be warranted in the management of suspected increased ICP. Recalling the goal of preserving CPP, one must address both ICP and MAP when deciding on appropriate management strategies. Early neurosurgical consultation is mandatory. Medical management might include the following: