Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis

INTRODUCTION — The clinical manifestations and diagnosis of elevated ICP in children will be reviewed here.

The management of elevated ICP in children, the evaluation of stupor and coma in children, and initial management of children with severe traumatic brain injury are discussed separately. (See "Elevated intracranial pressure (ICP) in children: Management" and "Evaluation of stupor and coma in children" and "Severe traumatic brain injury (TBI) in children: Initial evaluation and management".)

BACKGROUND — Elevated ICP is a potentially devastating complication of neurologic injury. In children, increased ICP is most often a complication of traumatic brain injury; it may also occur in children who have hydrocephalus, brain tumors, intracranial infections, hepatic encephalopathy, or impaired central nervous system venous outflow (table 1). Successful management of children with elevated ICP requires prompt recognition and therapy directed at both reducing ICP and reversing its underlying cause. Early recognition of elevated ICP can prevent neurologic sequelae and death.

PHYSIOLOGY

Intracranial pressure — The range of normal cerebrospinal fluid (CSF) pressure in children (10^th to 90^th percentile) at the time of lumbar puncture is 12 to 28 cmH₂O (9 to 21 mmHg) [1-3]. Measured ICP >20 mmHg (27 cmH₂O) for longer than five minutes with signs or symptoms is generally regarded as the threshold for treatment [4]. Occasional transient elevations may occur with physiologic events, including sneezing, coughing, or Valsalva maneuvers. However, sustained elevations above this pressure are abnormal [5].

The intracranial compartment is protected by the skull, a rigid structure with a fixed internal volume; the intracranial contents include (by volume) [6]:

●Brain parenchyma – 80 percent

●Cerebrospinal fluid (CSF) – 10 percent

●Blood – 10 percent

ICP is the pressure of CSF inside the cerebral ventricles, which is determined by cerebral blood flow (CBF) and CSF circulation. The Davson equation describes this relationship [7]:

Where P_ss is the sagittal sinus pressure, I_formation is the CSF formation rate, and R_CSF is the resistance to CSF outflow. The range of normal values for these variables are:

●Sagittal sinus pressure (P_ss) – 5 to 8 mmHg

●CSF formation rate (I_formation) – 0.3 to 0.4 mL/min

●Resistance to CSF outflow (R_CSF) – 6 to 10 mmHg/mL/min

Measured ICP is often greater than the calculated value because of a vascular component, which is probably a result of pulsation in the arterial bed and the interaction between pulsatile arterial inflow and venous outflow curves, cardiac function, and cerebral vasomotor tone [8]. Furthermore, all of these interrelationships may be altered in critically ill comatose patients with any of the conditions that increase ICP (table 1).

The anatomy and development of the cranial vault, the brain, and its vascular and CSF compartments also have an effect on ICP. The interrelationship between volume and compliance of each component of the intracranial compartment was recognized over 150 years ago and is known as the Monro-Kellie doctrine [9,10]. Because the overall volume of the cranial vault cannot change in the patient with closed cranial sutures, an increase in the volume of one component or the presence of pathologic components necessitates the displacement of other structures, an increase in ICP, or both [11]. Taken together with the Davson equation, it is clear that ICP is affected by various pathologies including:

●Parenchymal brain swelling

●Interstitial and vasogenic edema

●Alterations in cerebral blood volume (CBV)

●Obstruction of CSF outflow

●Focal cerebral perfusion deficits

●Variable levels of CBF

●Cerebrovascular carbon dioxide (CO₂) reactivity

●Cerebral vasculitis

The net result of this pathophysiology is elevated ICP along with significant risk of brain tissue herniation, ischemic syndromes, and death.

This process is demonstrated in the figure (figure 1). Normally, the intracranial components are in equilibrium. In a “closed system” (ie, closed sutures), initial compensation to increase in volume of a space-occupying lesion is by displacement of blood and CSF along the spinal axis, and ICP remains normal. When the limits of this compensation are reached; any additional increase in the volume of the mass lesion is accompanied by a corresponding increase in ICP (decompensated phase). The slope of the curve in the decompensated phase is steep, such that small changes in volume cause significant changes in ICP (figure 2) [11]. In infants with open cranial sutures and a non-ossified fontanel, the system should be considered as “open” and initial compensation occurs with bulging at the anterior fontanel. In slowly progressive change in volume, head growth will be affected by splaying of the cranial sutures, as seen in hydrocephalus.

Cerebral perfusion pressure — Cerebral perfusion pressure (CPP) is a clinical surrogate for the adequacy of cerebral perfusion. CPP is defined as mean arterial pressure (MAP) minus mean ICP.

CPP = MAP - ICP

Normal CPP in adults ranges from 50 to 70 mmHg; normal CPP in children younger than five years of age is probably lower than that in older children or adults, because children have lower systolic blood pressures, but normal limits have not been well established. However, based upon a normal ICP <20 mmHg and MAP >60 to 80 mmHg, depending upon age (where MAP = 1.5 x Age + 55 mmHg [12]), normal CPP in children can be calculated to be at least 40 to 60 mmHg [13]. When CPP falls below a critical level, either from hypotension or from a markedly elevated ICP, the brain receives inadequate CBF, and ischemic injury can occur [5,11].

Cerebral blood flow — When managing elevated ICP, the major goal is to maintain CBF. CBF is a function of the pressure drop across the cerebral circulation divided by the cerebrovascular resistance (CVR), as predicted by Ohm's law:

Where CAP is carotid arterial pressure, JVP is jugular venous pressure, and CVR is cerebrovascular resistance.

The following factors significantly impact CBF:

●Partial pressure of arterial oxygen (PaO₂) – PaO₂ has its most significant effects at levels below 50 mmHg, when it causes vasodilatation in an attempt to maintain the oxygen supply to the brain [11].

●Partial pressure of arterial carbon dioxide (PaCO₂) – Hypercapnia causes cerebral vasodilatation and increased CBF, whereas hypocapnia reduces CBF [11]. Because the response to changes in PaCO₂ is rapid, hyperventilation is an emergency intervention as a temporizing measure before neurosurgery during the acute management of increased ICP complicated by impending transtentorial and tonsillar herniation of brain tissue. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Therapeutic hyperventilation'.)

●Autoregulation – In the intact and normal cerebral circulation, CBF is maintained at a relatively constant rate by intrinsic cerebral mechanisms referred to as autoregulation. In addition to this global phenomenon, a region of brain tissue can also bring about an acute regional change in CBF. This coupling of local blood flow to local changes in metabolic activity is determined by a number of "neuro-energetic" signals [14]. A clinical illustration of this phenomenon is by the blood oxygen level-dependent ("BOLD") time series used in functional magnetic resonance imaging (fMRI) that can show "activated" regions with mental tasks. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Therapeutic hyperventilation'.)

At a global level, cerebral autoregulation adjusts CBF through changes in CVR. In adults, changes in CVR can maintain constant CBF at mean arterial pressures of 60 to 150 mmHg [15]. However, this "plateau" is under many influences including level of sympathetic activity and baseline PaCO₂. In infants and children, the range of the plateau (with upper and lower limits) is going to differ to that identified in adults because of developmental differences in mean arterial pressure and level of sympathetic activity. Consequently, we do not know the precise lower limit in mean blood pressure at which CBF falls with declining blood pressure. Newer techniques, however, using near-infrared spectroscopy in babies with hypoxic-ischemic encephalopathy suggest that optimum mean arterial pressure can be identified [16].

Outside this range, the compensatory mechanisms break down and inadequate or excessive perfusion can occur [11,15]. The upper and lower limits of autoregulation are shifted to the right in patients with chronic hypertension, such as patients with malignant hypertension and posterior reversible encephalopathy syndrome, in whom acute reductions in blood pressure can produce ischemic symptoms (figure 3). In addition, autoregulation may be impaired in the setting of neurologic injury, particularly in children, in whom rapid and severe brain swelling may result [17]. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Autoregulation'.)

PATHOPHYSIOLOGY

Cerebral edema — Cerebral edema may arise from a variety of clinical conditions (table 2). Therapeutic options for cerebral edema depend, in part, upon the type of edema:

●Cytotoxic or cellular edema – Cytotoxic or cellular edema is caused by intracellular swelling secondary to direct cell injury. This form of edema is common in patients who have severe cerebral injuries such as traumatic brain injury, traumatic axonal injury, or hypoxic-ischemic injury.

With these injuries, brain cells are often irreversibly injured, and therapy has little effect on eventual outcome [18]. By contrast, reversible edema can occur with water intoxication.

●Vasogenic edema – Vasogenic edema results when increased permeability of capillary endothelial cells permits fluid to escape into the extracellular space. Neurons are not primarily injured. Vasogenic edema is seen with tumors, intracranial hematomas, infarcts, abscesses, and central nervous system infections.

Therapy to decrease the edema may prevent secondary ischemic injury to surrounding brain tissue because neurons are not primarily injured [18]. Steroid therapy may be beneficial for vasogenic edema that occurs in the setting of mass lesions.

●Interstitial edema – Interstitial edema is characterized by increased fluid in the periventricular white matter. Increased cerebrospinal fluid (CSF) hydrostatic pressure, as occurs with hydrocephalus, is the most common cause.

Interstitial edema responds to therapies to reduce CSF pressure.

Trauma — After head trauma, a complex series of pathophysiologic changes may occur and contribute to increased ICP [11]:

●Loss of autoregulation resulting in excessive cerebral blood flow (CBF)

●Increased CSF production in response to cerebral hyperemia

●Hypercapnia or hypoxia, which may cause vasodilation and increased CBF (see 'Cerebral blood flow' above)

●Cerebral vessel vasospasm, which may cause regional ischemia and swelling in a vascular distribution [19]

●Herniation, brain swelling, or subarachnoid hemorrhage, which may obstruct the flow of CSF

●Epidural or subdural hematomas, cerebral contusions, or cerebral edema, which increases the volume of brain parenchyma with potential for decrease in blood and CSF volume

The combination of these changes can rapidly exceed the limits of intracranial compensation, leading to an increase in ICP and subsequent herniation or ischemia (focal or global). Intracranial hypertension may manifest immediately but more often occurs in the first 48 hours and peaks at day 3 to 5 after injury. (See 'Physiology' above.)

Brain herniation syndromes — Herniation of brain tissue can cause injury by compression or traction on neural and vascular structures. Herniation results when there is a pressure differential between the intracranial compartments and can occur in four areas of the cranial cavity [20]:

●Transtentorial herniation is the most common type (figure 4). It results from downward displacement of supratentorial brain tissue into the infratentorial compartment and can be caused by supratentorial mass lesions, diffuse brain swelling, focal edema, or acute hydrocephalus. Transtentorial herniation can cause compression of the third cranial nerve, the upper brainstem, and the cerebral peduncles as well as distortion or traction of the superior portion of the basilar artery and the posterior cerebral arteries, leading to occipital lobe infarction.

Furthermore, increased pressure in the frontal lobes causes posterior displacement over the lesser wing of the sphenoid bone which can cause carotid artery compression with anterior and middle cerebral artery infarction.

●Subfalcine herniation occurs when increased pressure in one hemisphere displaces brain tissue under the falx cerebri. Subfalcine herniation can cause compression of the anterior cerebral artery and extensive infarction of the frontal and parietal lobes.

●Foramen magnum herniation occurs when downward pressure forces the cerebellar tonsils into the foramen magnum, where they compress the medulla oblongata and upper cervical spinal cord.

CLINICAL MANIFESTATIONS — The clinical presentation of elevated ICP varies by the age of the child and whether the rise in pressure is gradual or acute. Features related to the underlying cause such as brain tumor or severe head trauma (including abusive head trauma) may also be evident.

Patient age — Among infants with chronic, progressive elevation in ICP (eg, slow-growing brain tumor), macrocephaly for age (figure 5 and figure 6) with a bulging anterior fontanel is the most common presenting feature because unfused cranial sutures can accommodate rising ICP without acutely compromising neurologic status. In addition, infants and young children may be unable to articulate certain symptoms (eg, headaches) and therefore are more likely to present with irritability. Alternatively, infants may display lethargy, lack of interest in their surroundings, and poor feeding.

Nausea and vomiting are common presenting symptoms at any age. In older children and adolescents, other common findings include headache, visual disturbance, abnormal gait, poor coordination, and papilledema.

Acutely elevated ICP — Acute elevation of ICP is an emergent condition that requires prompt recognition and management. Important findings include:

●Headache – In verbal children, headache is an early sign of acute elevation of ICP and, as noted below, transtentorial herniation.

●Vomiting – Vomiting frequently accompanies acute rises in ICP.

●Altered mental status – In patients with an acute increase in ICP (eg, severe head trauma or intracranial hemorrhage), abrupt onset of altered mental status with obtundation or coma may arise from direct brain injury or herniation.

●Papilledema – Papilledema (picture 1), if present, can confirm the presence of intracranial hypertension. However, papilledema may be absent in patients with acute elevation ICP because it takes several days to become apparent. Thus, absence of papilledema does not exclude elevated ICP [21,22].

●Hypertension with bradycardia or tachycardia – In children, increased ICP causes hypertension and either bradycardia or tachycardia. It is important to use age-based standards for heart rate (table 3) and blood pressure (table 4 and table 5). The combination of systemic hypertension, bradycardia, and respiratory depression (Cushing triad) is a late sign of impending herniation (table 6).

●Transtentorial herniation – In addition to vital sign changes, the earliest clinical signs of transtentorial herniation include (figure 4 and table 6):

•Headache

•Altered level of consciousness

•Pupillary changes (eg, anisocoria) with intact oculocephalic reflex and cold caloric response (figure 7)

•Abnormal breathing patterns (eg, Cheyne Stokes respirations)

•Maintained localization of noxious stimuli if paralysis is not present

As transtentorial herniation progresses the respiratory pattern changes, pupils become midposition and fixed, and motor response becomes decorticate, decerebrate, or absent (figure 8). Selected patients with posterior displacement of the brain over the lesser wing of the sphenoid bone due to increased pressure in the frontal lobes of the brain may develop hemiplegia, coma, and death due to compression of the anterior and middle cerebral arteries.

●Other herniation – Characteristic features identify other types of herniation:

•Foramen magnum herniation – Patients with foramen magnum herniation may have downbeat nystagmus, bradycardia, bradypnea, and hypertension; these findings may be exacerbated by neck flexion and improve with neck extension.

•Subfalcine herniation – Clinical features of subfalcine herniation include unilateral or bilateral weakness, loss of bladder control, and coma.

●Other findings – Less common findings of acute intracranial hypertension consist of:

•A natural preference for the "knee-chest" position

•Seizures

•Spontaneous upper eyelid ecchymosis adjacent to the lid margin when an abrupt increase in cerebral venous pressure is transmitted via the cavernous sinus to the orbital venous system [23]

•Transient (5 to 15 minutes) epidermal flushing involving the upper chest, face, or arms during the period of deterioration

●Findings of child abuse – Retinal hemorrhages may be present in infants with acute brain injury and increased ICP caused by abusive head trauma. Other findings such as cutaneous bruising, fractures, or visceral injuries may also be present (table 7). (See "Child abuse: Eye findings in children with abusive head trauma (AHT)" and "Physical child abuse: Recognition", section on 'Red flag physical findings'.)

Subacute or chronic ICP elevation — Key findings of subacute or chronic elevation of ICP include:

●Headache – Headache is one of the earliest symptoms of increased ICP. Certain headache features suggest increased ICP as described in the table (table 8). Infants and preverbal children who cannot express the presence of headache more commonly present with irritability. (See "Headache in children: Approach to evaluation and general management strategies", section on 'Worrisome findings'.)

●Vomiting – Vomiting, often worse in the morning, occurs due to buildup of ICP overnight while the patient is recumbent and venous drainage is decreased.

●Abnormalities of vertical gaze (Parinaud syndrome) – Abnormalities of vertical gaze including sunsetting, a downward gaze preference or an inability to look upwards are found in pediatric patients with hydrocephalus, brain tumor, or stroke due to enlargement of the third ventricle (table 9).

●Visual changes – Visual changes, such as vision loss (typically peripheral before central vision) or double vision (caused by palsies of cranial nerves III (oculomotor), IV (trochlear), or VI (abducens) suggest brainstem pathology (see "Detailed neurologic assessment of infants and children", section on 'III (oculomotor), IV (trochlear), and VI (abducens)'). Infants and young children who cannot complain of diplopia may squint, cover one eye with their hand, or tilt their head to one side (picture 2).

●Papilledema – Papilledema (picture 1) is a specific finding of elevated ICP. However, an adequate funduscopic examination is frequently difficult to obtain in infants or young children.

●Neurologic – Abnormal coordination and ataxia with gait disturbance suggests a posterior fossa lesion that is frequently associated with elevated ICP. (See "Clinical manifestations and diagnosis of central nervous system tumors in children", section on 'Tumor location'.)

●Findings of a brain tumor – Clinical features that suggest progressive elevation of ICP due to a brain tumor include (see "Clinical manifestations and diagnosis of central nervous system tumors in children", section on 'Common presenting signs and symptoms' and "Clinical manifestations and diagnosis of central nervous system tumors in children", section on 'Neurocutaneous syndromes'):

•Growth abnormalities

•Neck pain or stiffness

•Behavior or personality change; in older children declining grades in school

•Known risk factor for intracranial pathology (eg, neurocutaneous syndrome, macrocephaly, or hormonal abnormalities)

•Focal weakness or paralysis

•Ataxia and gait abnormalities

DIAGNOSIS

Approach — Although discussed separately, the assessment and management of elevated ICP are performed jointly in practice. The diagnosis of elevated ICP is typically established by neuroimaging or other noninvasive means in pediatric patients with suggestive clinical findings (eg, headache, vomiting, vision changes, altered mental status, or findings of herniation (table 6)). Papilledema, when present, is specific for intracranial hypertension but has low sensitivity. (See 'Clinical manifestations' above and 'Detection of papilledema' below.)

Direct measurement of increased ICP >20 mmHg (27 cmH₂O) using an external ventricular drain or intraparenchymal ICP monitor is the definitive way to confirm the presence of intracranial hypertension. However, invasive measurement of ICP is reserved for the most severely affected children in whom the benefits of direct measurement outweigh the risks of bleeding and infection (eg, Glasgow coma score [GCS] ≤8 (table 10) following head trauma or diagnosed with a condition that warrants aggressive treatment to manage ICP) [24].

In awake patients with findings that indicate subacute or chronic elevation of ICP (eg, headache, peripheral vision loss, and papilledema) but a nonfocal neurologic examination and normal neuroimaging, elevated opening pressure on lumbar puncture (>27 cmH₂O) can establish the diagnosis of idiopathic intracranial hypertension (pseudotumor cerebri). (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis", section on 'Lumbar puncture' and "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis", section on 'Diagnosis'.)

The diagnosis of intracranial hypertension can be challenging, especially when the elevation is subacute or chronic. In infants with unfused sutures, progressive enlargement of the cranial vault due to increased ICP can be initially accommodated without major clinical decompensation. In older children, early symptoms such as headache or vomiting are nonspecific, and unless there is a high index of suspicion, as the course progresses, an altered level of consciousness may hinder the diagnosis. Nonetheless, early diagnosis is of utmost importance because appropriate therapy can minimize or prevent permanent neurologic injury.  

Noninvasive detection of elevated ICP — In children, neuroimaging is the primary means of noninvasively detecting elevated ICP [24]. However, findings of increased ICP take time to develop and are frequently not present during the first 24 hours in patients with acute elevation of due to cerebral edema.

Computed tomography — For detection of acute elevation of ICP, computed tomography (CT) of the brain without contrast is the initial study of choice because it is noninvasive, can be obtained quickly in most hospitals without sedating the patient, and is more readily available than magnetic resonance imaging [24]. Head CT should be obtained as soon as the child is stabilized so that emergency therapy, if indicated, can be initiated. The goal of the emergency CT is to assess for a surgical cause of raised ICP that necessitates immediate neurosurgery (eg, epidural hematoma or acute, obstructive hydrocephalus). Head CT is also the best imaging study for the initial evaluation of intracranial injuries caused by head trauma. (See "Severe traumatic brain injury (TBI) in children: Initial evaluation and management", section on 'Imaging'.)

Findings consistent with elevated ICP on head CT include [24,25]:

●Midline shift

●Effacement of the basilar cisterns (image 1)

●Effacement of the sulci (image 1)

●Thumbprinting referring to increased gyral markings on the inner table of the skull in patients with chronically elevated ICP

●In adults, increased optic nerve sheath diameter (>6 mm); specific criteria for children have not been established, but >6 mm is used at the author’s institution. Based upon preliminary evidence using ocular ultrasound, different thresholds may exist for infants with open fontanelles and children 1 year of age and younger [26]. (See 'Ocular ultrasound' below.)

Head CT may also demonstrate the underlying etiology of elevated ICP such as cerebral edema, mass lesion, or hemorrhage (table 1).

However, based upon small observational studies in children with head trauma or nontraumatic coma and experience in adults with severe head trauma, patients without these findings on initial CT may have elevated ICP in up to 15 percent of cases [27,28]. Abnormalities on head CT may develop within the first few days after a closed head injury in up to one-third of patients. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Indications'.)

Thus, head CT findings must be interpreted cautiously, especially in children with head injury. Children with no findings of increased ICP on head CT but in whom elevated ICP is suspected based upon clinical findings such as headache, vomiting, vision changes, altered mental status, or findings of herniation should still receive expectant management and undergo alternative means to identify elevated ICP as follows:

●Direct measurement of ICP by an external ventricular drain or intraparenchymal ICP monitor – Patients with head injury and a GCS ≤8 or showing signs of impending herniation (see "Severe traumatic brain injury (TBI) in children: Initial evaluation and management", section on 'Ongoing management')

●Repeat CT or magnetic resonance imaging (MRI) at 12 to 24 hours – In general, if there has been no change in the patient’s condition “routine” repeat imaging is not needed. However, repeat imaging is important in the following circumstances:

•For patients with head injury or a space-occupying lesion on initial head CT (eg, subdural hematoma, brain tumor, or cerebral abscess), yet they have not undergone surgical intervention or direct measurement of ICP. Such imaging is needed when clinical assessment is not possible because of other interventions (eg, endotracheal tube, mechanical ventilation, sedation, and neuromuscular blockade)

•For patients with head injury or a space-occupying lesion on initial head CT, who in the intervening period have deteriorated.

●Lumbar puncture – Only indicated in awake patients with features of elevated ICP (eg, headache, papilledema, peripheral vision loss) but normal neurologic examination suggesting idiopathic intracranial hypertension (pseudotumor cerebri) (see "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis", section on 'Lumbar puncture')

Magnetic resonance imaging — MRI of the brain is more accurate for detecting elevation of ICP than CT but is less accurate than invasive measurement of ICP. It is also less available, takes longer to perform, and requires sedation in infants and young children or otherwise uncooperative patients [24]. MRI is a suitable alternative to head CT in patients with intact mental status and neurologic examination in whom chronically elevated ICP is suspected. As for CT, MRI findings of midline shift and effacement of the basilar cisterns or sulci indicate elevated ICP.

Though pediatric evidence is limited or lacking, the following measurements have also been correlated with intracranial hypertension in small studies:

●Elastance index that measures the ratio of ICP change to volume change during the cardiac cycle, high elastance occurs in brains with low compliance due to elevated ICP [29]

●Cerebral blood flow [30]

●CSF flow velocity through the cerebral aqueduct [31]

●In adults, optic nerve sheath diameter, although pediatric criteria are emerging [32] (see 'Ocular ultrasound' below)

However, further studies are needed before these MRI measurements can be routinely employed in children.

MRI does have greater sensitivity for detecting conditions that can cause cerebral edema (table 2) than computed tomography of the head. In clinical practice, these different forms of edema can be differentiated by comparing images from T2-weighting (T2-W), diffusion-weighting (DW), and apparent diffusion coefficient (ADC) sequences [25]. For example, three clinical illustrations of interstitial edema, cytotoxic/cellular edema, and vasogenic edema are, respectively, acute hydrocephalus, cerebral infarction, and posterior reversible encephalopathy syndrome (PRES). All three conditions show hyperintensity of signal in the affected region on T2-W imaging. Signal hyperintensity on DW imaging is seen in regions affected by cerebral infarction and periventricular regions in acute hydrocephalus. ADC is large and anisotropic in PRES, large in periventricular regions in acute hydrocephalus, and low with reduced anisotropy in infarcted tissue [18].

By contrast, although CT of the head can identify the presence of cerebral edema, it does not distinguish the type of edema [25].

Detection of papilledema — Papilledema on funduscopy has low sensitivity for intracranial hypertension as demonstrated in small studies of children with shunt failure or idiopathic intracranial hypertension (pseudotumor cerebri) [33,34]. Furthermore, papilledema takes time to develop and is typically not present in patients with increased ICP caused by acute head injury or hemorrhage. However, when present, papilledema can be a specific indicator of elevated ICP.

Fundus photography and optical coherence tomography (OCT) provide alternative methods to detect elevated ICP using images of the optic disk [35]. OCT has been used to monitor papilledema in children [35,36]. Although potentially better than funduscopy for detecting papilledema caused by elevated ICP, these methods require patient cooperation and have the same limitations as funduscopy for identifying acute intracranial hypertension.

Ocular ultrasound — Ocular nerve sheath diameter (ONSD) can be measured using ocular ultrasound, and limited evidence supports age-based normal values [24,26,37]. Threshold values that may correlate with an ICP ≥20 mmHg have also been proposed [24,26]. However, association with increased ICP by invasive monitoring in children has been variable [24,26,38]. Thus, we do not use ONSD for detection or monitoring of increased ICP pending further study.

Invasive measurement of ICP — Invasive measurement of ICP definitively establishes the presence of intracranial hypertension. However, because of potential complications of infection and bleeding and the need for placement by a pediatric neurosurgeon, invasive measurement is reserved for the most critically ill patients [24].

Intracranial monitoring with an external ventricular drain or intraparenchymal ICP monitor should be strongly considered in pediatric patients with a GCS ≤8 (table 10) after head trauma or who are diagnosed with a condition that warrants aggressive medical or surgical treatment to manage ICP based upon clinical findings and results of neuroimaging [4]. However, evidence is lacking to guide this decision in children. Furthermore, in a retrospective, database, propensity-weighted analysis of the impact of ICP monitors in over 3000 children suffering with severe TBI, functional outcomes, specifically survival, were not associated with the use of invasive monitoring [39]. Further studies are needed to help with clinical decision-making (ie, examination of treatment used along with the monitoring). Until that time, use of ICP monitoring remains a recommendation for severe TBI (GCS ≤8) in pediatric patients.

Intracranial monitoring in adults is discussed separately. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'ICP monitoring'.)

A detailed discussion of neurologic monitoring in comatose children with elevated ICP is beyond the scope of this topic but is addressed in the reference [40].

Ancillary studies — In addition to neuroimaging, ancillary studies serve to identify specific etiologies of elevated ICP (eg, meningitis or encephalitis), comorbid conditions in children with severe head trauma, and to differentiate elevated ICP from other causes of altered mental status (eg, hypoglycemia, metabolic encephalopathy, intoxication, or nonconvulsive status epilepticus).

Laboratory studies — Patients with known trauma or suspected abusive head injury should undergo laboratory evaluation for other injuries as discussed separately. (See "Trauma management: Approach to the unstable child", section on 'Adjuncts to the primary survey' and "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Laboratory studies'.)

Patients presenting with altered consciousness but no evidence of trauma should undergo a rapid bedside test for blood glucose and basic laboratory testing including (see "Evaluation of stupor and coma in children", section on 'Laboratory testing'):

●Serum electrolytes, calcium, magnesium

●Blood urea nitrogen, creatinine

●Arterial blood gas or pulse oximetry with measurement of venous blood gas

●Complete blood count

●Additional studies in febrile patients with possible central nervous system infection include:

•Blood culture

•Urinalysis

•Urine culture

•If lumbar puncture can be safely performed, cerebrospinal fluid (CSF) studies including (see 'Lumbar puncture' below):

-CSF cell count

-CSF glucose and protein

-CSF Gram stain, culture, and, as indicated, polymerase chain reaction for specific pathogens (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Laboratory evaluation' and "Acute viral encephalitis in children: Clinical manifestations and diagnosis", section on 'Laboratory evaluation')

●Additional studies in pediatric patients in whom intoxication is suspected based upon history or physical findings (table 11) are as follows:

•Measured serum osmolality

•Blood ethanol concentration

•Urine drug screen for drugs of abuse

●In young infants in whom metabolic disease is suspected, evaluation according to presenting features (table 12) (see "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management", section on 'Evaluation of specific critical presentations')

Lumbar puncture — LP, if necessary for diagnosis, should be deferred until after neuroimaging in any patient in whom intracranial hypertension is suspected, especially those patients with findings of impending herniation (table 6). (See 'Clinical manifestations' above.)

Furthermore, because neuroimaging does not always identify elevated ICP, patients with focal neurologic findings should not routinely undergo LP, regardless of radiographic findings. (See 'Computed tomography' above and 'Magnetic resonance imaging' above.)

These precautions are essential to avoid precipitating herniation across the tentorial notch or into the foramen magnum. LP decreases pressure in the region below the tentorium. If elevated pressure above the tentorium exists, then the pressure gradient between compartments, if large enough, can cause herniation.

In patients in whom central nervous system infection is a strong consideration, deferral of lumbar puncture should not delay the initiation of empiric antibiotic therapy (table 13). (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Avoidance of delay'.)

When an LP is performed for evaluation of a child with suspected elevated ICP, an opening pressure should be obtained. (See "Lumbar puncture in children", section on 'Use of manometer'.)

The contraindications to lumbar puncture in children are discussed in detail separately. (See "Lumbar puncture in children".)

Electroencephalogram — Rarely, nonconvulsive status can present with altered mental status and physical findings that suggest increased ICP. EEG can identify this condition in patients whose neuroimaging and clinical progression do not correspond with what is expected in patients with intracranial hypertension.

DIFFERENTIAL DIAGNOSIS — Whenever suspected, the first priority is to confirm the diagnosis of intracranial hypertension, prevent further decompensation, and treat the underlying cause. The physician should also be aware of the conditions that can mimic acute or chronic elevations of ICP as discussed below. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Ongoing Management'.)

Acute intracranial hypertension — Conditions that can mimic acute elevations of ICP consist of:

●Hypoglycemia – Hypoglycemia may present with abrupt onset of altered mental status and can cause coma with focal seizures or a focal neurologic deficit. It warrants early recognition by measurement of rapid blood glucose and emergency treatment to prevent permanent brain damage (table 14). (See "Approach to hypoglycemia in infants and children", section on 'Treatment'.)

●Metabolic encephalopathies, other than hypoglycemia – Metabolic coma in children usually occurs as a progression from delirium to stupor to coma, but more fulminant cases may present in coma. A fluctuating examination is common; deficits can include abnormal brainstem reflexes, hypotonia, and even posturing in severe cases. However, focal neurologic findings and anisocoria are uncommon in metabolic coma. Multifocal myoclonus is very suggestive of a metabolic etiology. Potential etiologies of metabolic coma are provided in the table (table 15) and are discussed in detail separately. (See "Acute toxic-metabolic encephalopathy in children".)

●Acute drug intoxication – Encephalopathy resulting from the toxic effect of medication is an important diagnostic consideration in a patient in whom intracranial hypertension is suspected because of the typically abrupt onset of encephalopathy. This condition can result from therapeutic overdose, unintentional ingestion, or deliberate abuse. Drugs that result in coma when present in high concentration include sedatives, anticholinergic agents, and salicylates (table 16). In many instances, physical findings can differentiate intoxication from increased ICP (table 11). Furthermore, drug intoxication with these agents is not usually associated with focal neurologic findings. (See "Approach to the child with occult toxic exposure" and "Acute toxic-metabolic encephalopathy in children", section on 'Drugs and toxins'.)

Chemotherapy may result in similar states regardless of drug level, and is often associated with signs of acute leukoencephalopathy on brain magnetic resonance imaging (MRI) (high signal on T2 and fluid attenuated inversion recovery [FLAIR]) and even changes in diffusion-weighted imaging (DWI), due to cytotoxic edema, especially with methotrexate use. (See "Acute toxic-metabolic encephalopathy in children", section on 'Immunosuppressive and immune modulating agents'.)

●Nonconvulsive status epilepticus – Nonconvulsive status epilepticus may present with a variety of symptoms and signs, including significant alterations in mental status. Electroencephalogram (EEG) confirms the diagnosis. EEG is warranted in critically ill patients who are obtunded or comatose and do not have clear findings of intracranial hypertension. (See "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis", section on 'Patient selection for EEG' and "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis", section on 'Clinical features'.)

●Hemiplegic migraine headache – Hemiplegic migraine is characterized by migraine attacks with motor weakness during the aura phase. Attacks may variably include severe headache, scintillating scotoma, visual field defect, numbness, paresthesia, unilateral weakness, aphasia, fever, lethargy, coma, and seizures. The symptoms can last for hours to days, or rarely weeks. The diagnosis is suggested by episodic occurrence of hemiplegia and response to specific treatment for migraine. (See "Hemiplegic migraine", section on 'Clinical manifestations' and "Hemiplegic migraine", section on 'Diagnosis'.)

Chronic intracranial hypertension — Headache is the most common presenting symptom of chronically elevated ICP (table 8). However, headache is also a frequent symptom of benign conditions in children, especially self-limited febrile illnesses (table 17). A careful history and physical examination can usually identify patients with concerning findings of intracranial hypertension. (See 'Acutely elevated ICP' above and 'Subacute or chronic ICP elevation' above.)

The acute evaluation of headaches in children is discussed separately. (See "Emergency department approach to nontraumatic headache in children", section on 'Diagnostic approach'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Increased intracranial pressure and moderate-to-severe traumatic brain injury".)

SUMMARY AND RECOMMENDATIONS

●Causes and treatment threshold – In children, increased ICP is most often a complication of traumatic brain injury; it may also occur in children who have hydrocephalus, brain tumors, intracranial infections hepatic encephalopathy, or impaired central nervous system venous outflow (eg, liver failure) (table 1). Measured ICP >20 mmHg (27 cmH₂O) is generally regarded as the threshold for treatment. (See 'Physiology' above and "Elevated intracranial pressure (ICP) in children: Management", section on 'Ongoing Management'.)

●Clinical manifestations – Acute elevation of ICP is an emergency condition. Important findings include (see 'Acutely elevated ICP' above):

•Headache (verbal children)

•Vomiting

•Abrupt onset of obtundation or coma

•Papilledema (picture 1) which may not be present in patients with acute elevations of ICP

•Hypertension (table 4 and table 5) with bradycardia or tachycardia (table 3)

•Signs of herniation (figure 4 and table 6)

•Spontaneous upper eyelid ecchymosis adjacent to the lid margin

•Retinal hemorrhages, cutaneous bruising, fractures, or visceral injury (table 7) in victims of abusive head trauma

Among infants with chronic, progressive elevation in ICP (eg, slow-growing brain tumor), macrocephaly for age (figure 5 and figure 6) with a bulging anterior fontanel is the most common presenting feature. In addition, infants and young children may be unable to articulate certain symptoms (eg, headaches) and therefore are more likely to present with irritability. Alternatively, infants may display lethargy, lack of interest in their surroundings, and poor feeding. (See 'Patient age' above.)

●Subacute or chronic ICP elevation – Among children with chronically elevated ICP, key findings are as follows (see 'Subacute or chronic ICP elevation' above):

•Headache (table 8)

•Vomiting, often worse in the morning due to buildup of ICP overnight while recumbent

•Abnormalities of vertical gaze (eg, downward gaze preference [sunsetting] or inability to look upwards)

•Vision loss or double vision; in young children diplopia may cause squinting or a head tilt (picture 2)

•Papilledema (picture 1)

•Ataxia, poor coordination, or abnormal gait suggesting a posterior fossa lesion

•Other findings of a brain tumor such as growth abnormalities, neck pain or stiffness, behavior change, or focal weakness or paralysis

●Diagnosis – Although discussed separately, the assessment and management of elevated ICP are performed jointly in practice (algorithm 1). The diagnosis of elevated ICP is typically established by neuroimaging or other noninvasive means in pediatric patients with suggestive clinical findings (eg, headache, vomiting, vision changes, altered mental status, or findings of herniation (table 6)). Papilledema, when present, is specific for intracranial hypertension but has low sensitivity. (See 'Approach' above and 'Noninvasive detection of elevated ICP' above.)

Invasive measurement of ICP definitively establishes the presence of intracranial hypertension. Intracranial monitoring with an external ventricular drain or intraparenchymal ICP monitor placed by a neurosurgeon is usually indicated in pediatric patients with a Glasgow coma score (GCS) ≤8 (table 10) after head trauma or who are diagnosed with a condition that warrants aggressive medical or surgical treatment to manage ICP based upon clinical findings and results of neuroimaging. (See 'Invasive measurement of ICP' above.)

●Ancillary studies – In addition to neuroimaging, ancillary studies serve to identify specific etiologies of elevated ICP (eg, meningitis or encephalitis), comorbid conditions in children with severe head trauma, and to differentiate elevated ICP from other causes of altered mental status (eg, hypoglycemia, metabolic encephalopathy, intoxication, or nonconvulsive status epilepticus). (See 'Ancillary studies' above and 'Differential diagnosis' above.)

Lumbar puncture (LP), if necessary for diagnosis, should be deferred until after neuroimaging in any patient in whom intracranial hypertension is suspected, especially those patients with findings of impending herniation. Furthermore, because neuroimaging does not always identify elevated ICP, patients with focal neurologic findings should not routinely undergo LP, regardless of radiographic findings. (See 'Lumbar puncture' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Warren K Brasher, MD, who contributed to earlier versions of this topic review.