Introduction

Intracranial hypertension (IH) is a general term for excessive pressure within the cranial vault. It usually presents with headaches, alterations in the level of consciousness, visual disturbances, and kids’ developmental or cognitive delays. The etiologies for IH vary and are usually separated into two primary groups based on the etiology of the derangement—primary intracranial hypertension (also known as idiopathic intracranial hypertension or pseudotumor cerebri) and secondary intracranial hypertension (variable etiologies—trauma, hydrocephalus, infection, tumors, acute subarachnoid hemorrhage, Chiari malformation, medication-induced, etc.). Another way to categorize increased intracranial pressure is by severity and acuity. Sustained chronic intracranial hypertension usually is better tolerated and presented with chronic headaches, visual disturbances, and even developmental and cognitive delays. On the other hand, acute IH (e.g., traumatic brain injury) is not well tolerated and can lead to acute brain herniation—this was referred to by some as “brain codes”, which in analogy to cardiac codes, signify extreme cases of devastating neurological episodes that mandate immediate action to save brain tissue and prevent further injury and even death [1]. Besides specific etiologies that have a component of the mass lesion (brain tumor, intracranial bleeding, etc.) with or without secondary brain edema, most of the other etiologies pathophysiological mechanism leads to elevated pressure as a result of the secondary brain edema. Brain edema is traditionally classified as vasogenic or cytotoxic [1, 2]. Further understanding of the pathophysiology leads to the current paradigm stating this is a continuum process, with different stages and types of edema (usually cytotoxic edema, then ionic edema, and last vasogenic edema) [3]. Cytotoxic edema is created by progressive cell swelling mainly because of the accumulation of fluids and sodium. Vasogenic edema is primarily created by the disruption of the blood–brain barrier (BBB). This leads to the extracellular accumulation of fluid in the brain parenchyma.

The management paradigm of elevated intracranial pressure is based on pediatric traumatic brain injury research and management. Early detection of increased intracranial pressure is an essential first step to implement the right therapeutic measures [4]. In many cases, imaging and clinical evaluation is enough to diagnose elevation in intracranial pressure. In some cases, as part of diagnosis and monitoring of treatment’s effectiveness, direct ICP monitoring via intraparenchymal or intraventricular catheter is considered. Direct ICP measurement is considered by many the gold standard and the most reliable technique. However, although relatively low risk, it still bears the risk for intraparenchymal or ventricular hemorrhage as well as an intracranial infection [5]. This leads to the development of a variety of non-invasive diagnostic tools to measure ICP [6]. The use of direct ICP measurement for non-traumatic etiologies is highly controversial, and its use is judged based on the case and the possible benefit of invasive monitoring [7,8,9].

This review thoroughly describes the different etiologies, suggested diagnosis, monitoring, and treatment for non-traumatic etiologies that lead to IH in the pediatric population.

Methodology

A thorough literature review was made using PubMed. We used general keywords for elevated intracranial pressure concerning the pediatric population (e.g., pediatric elevated intracranial hypertension, pediatric elevated intracranial pressure, elevated intracranial pressure in children). After reviewing the non-traumatic etiologies, we chose the most commonly discussed etiologies in the literature and ran another literature review for each subcategory. These etiologies are described in this review based on the different papers that were reviewed for each subcategory.

Core treatment paradigm

The treatment paradigm derived mainly from trauma studies and the development of Brain Trauma Foundation Guidelines for traumatic brain injuries [10,11,12]. Most clinicians agree that when the suspicion for elevated ICP is present, a stepwise tier directed paradigm should be initiated, with an elevation of the head of the bed, control blood pressure and glycemic status, and initiation of hyperosmolar treatment as needed. In the pediatric population, Yildizdas et al. [13] conducted a retrospective study of 67 children with cerebral edema caused by different etiologies. In their research, the endpoint was the duration of the comatose state and mortality for patients that were treated aggressively for elevated ICP by either mannitol, hypertonic saline, or a combination of the two. They found that those treated by mannitol did worse and deduced that hypertonic saline has some advantages over mannitol. Yet, other publications failed to achieve the same results and even found mannitol benefits like treatment choice [14, 15]. In 2016, Burgess et al. published a systematic review of RCTs comparing the two modalities in TBI treatment [16]. They stated that if taking all considerations into account and not just reducing ICP, there is no superiority of any agent over the other. They concluded that choice of therapy could be decided based on safety and that in different scenarios, different agents can be used when taking the safety profile into account [16].

The paradigm for non-traumatic elevated ICP is different in several aspects, and one of them is the possible use of high dose corticosteroids, which can be very beneficial in cases of intracranial mass effect like a new brain tumor but can be even harmful to some degree when given in the case of IH as a result of brain trauma [10, 12]. If the condition continues to evolve, most agree there is a need to control ICP and cerebral perfusion pressure (CPP) by more aggressive measures like intubation, ventilation, and possible invasive ICP monitoring. The use of induced hypothermia is still highly controversial, even for the pediatric age group. Advocates mention the good response that was observed among neonates treated with hypothermia for hypoxic-ischemic insults [17, 18]. In a multicenter phase III randomized controlled trial for severe pediatric TBI comparing induced hypothermia versus maintaining normothermia, it was found that induced hypothermia did not lead to greater mortality but also did not achieve a better neurological outcome for the patients (much more patients needed intervention in the normothermia group, but it did not reach statistical significance) [19]. The latest update for the pediatric age group from the brain trauma foundation published in 2019, still describes the controversy with a Level II evidence stating there is no benefit over normothermia for improving outcome. Yet, for overall ICP reduction, there is a level III recommendation to use moderate hypothermia [12]. For the non-traumatic etiologies of pediatric IH, there is no evidence to support either way, and we advocate using extreme caution when choosing this tool. In the case where ICP is refractory, the use of paralytic agents can be discussed (although controversial) and the consideration for barbiturate-induced coma or decompressive craniectomy. Hemispheric decompressive craniectomy is known to increase the cranial cavity volume and thus reduce intracranial pressure, increase perfusion pressure, and preserve cerebral blood flow [20]. The use of decompressive craniectomy in non-traumatic IH settings is again highly controversial, with no evidence to support its use besides some small series and case reports.

Different etiologies for non-traumatic pediatric intracranial pressure

Pediatric hypoxic brain injury usually includes injuries with devastating results, such as near-drowning or prolonged resuscitation after cardiac arrest. The management of this kind of injury usually will consist of supportive systemic treatment with some measurement for controlling brain swelling. There is a big controversy regarding intracranial pressure monitoring, mainly because it appears not to alter the outcome [21]. Another group of pathological conditions that is atraumatic and known to be related to significant brain edema or swelling is related to metabolic disorders, such as Reye’s syndrome. Past literature showed the benefit of ICP monitoring for Reye’s syndrome, but like near-drowning, invasive monitoring is quite controversial regarding other anoxic encephalopathies [8]. For fulminant hepatic failure, there is controversy as well, but a growing body of literature suggests the benefit of controlling the ICP even as a bridge for transplantation. The elevated ICP in high-grade liver encephalopathy is a leading cause of mortality, and aggressive measures to control it have shown benefit [22]. In a recent review regarding different pathologies that can lead to elevated intracranial pressure, the authors describe panel recommendations for various pathologies stating the insufficient literature and evidence regarding pathologies that are not TBI related [23]. The literature focuses mainly on the major pathologies, such as TBI, stroke, sinus vein thrombosis, IIH, and infections. There is even less published data regarding the pediatric age group, and hence the treatment paradigm is deduced from the adult age group literature. The treatment paradigm in many cases will be similar, as mentioned above. Still, there is a lack of evidence in many issues regarding the different treatment aspects (e.g., invasive ICP monitoring). In this review, we will focus on the significant etiologies discussed in the literature regarding pediatric non-traumatic elevated ICP.

Brain tumors

One of the significant non-traumatic etiologies of elevated ICP among the pediatric age group is mass-like lesions, such as brain tumors. The discussion of pediatric brain tumors and their treatment paradigm is lengthy and beyond this review’s scope. Most cases of elevated ICP that are related to brain tumors will be treated with debulking or resection of the tumor. In other cases, when secondary hydrocephalus cannot be relieved by tumor resection, CSF diversion will be needed.

Infections

Meningitis is an infection of the brain covering mainly the dura, arachnoid, and subarachnoid space. Encephalitis and brain abscesses are infections of the brain itself, either the grey or white matter fibers. The symptoms can vary widely from mild neurological changes with or without fever to severe neurological deterioration, septic shock, and even death. The imaging modality is usually MRI, focusing on T1 with gadolinium, T2, and FLAIR sequences.

Acute severe bacterial meningitis can develop into a severe infection across the central nervous system with devastating consequences [24,25,26,27]. The high mortality and morbidity rates are mainly due to raised intracranial pressure and herniation. Although better understanding has been achieved in recent years, the mortality rate is still very high with traditional therapies for increased ICP [28]. The treatment paradigm is derived mainly from the trauma setting or acute malignant stroke syndrome. One of the possible explanations is collateral damage, such as vascular injury (that can potentially lead to areas of cerebral ischemia and stroke), cerebritis, and the evolution of brain abscess. In some cases, vascular injury leads to small punctate hemorrhagic spots that eventually can evolve into a severe infection and even significant brain infarct [29, 30]. Encephalitis is an inflammation of the brain parenchyma that can be presented as a significant neurological deficit. It primarily involves the brain yet can involve the meninges in some cases (meningoencephalitis). The impairment of viral encephalitis can result from focal or diffuse inflammation and vascular arthropathies, including pediatric stroke [26]. Among the pediatric population, the most common form of encephalitis is infection from the Herpes simplex virus. The infectious manifestations are devastating, with more than 70% mortality rate is reported in untreated cases, and almost all the patients will not return to their neurological baseline [31, 32]. Treatment success depends mainly on early anti-viral treatment. A significant reduction in mortality (in some publications to 20%) and significantly favorable results (around half of the patients will go back to baseline) can be achieved with the administration of Acyclovir [32]. The disease-associated inflammatory process is usually focal and tends to classically affect the temporal lobe. However, in some cases, parenchymal hemorrhage and areas of necrosis can be developed within the involved area, leading to mass effect and intracranial hypertension. In severe cases, even to brain herniation [33]. The peak rise in ICP varies for the individual patient but has been described in adults around the 12th day of illness, whereas in children, the data are still lacking [34]. Barnett et al. demonstrated in their publication that within two weeks, half of the patients died due to severe mass effects causing a devastating elevation in intracranial pressure despite treatment to alleviate the pressure [34]. Hence, a better understanding of the patient’s ICP is needed in the setting of acute and severe encephalitis [35]. Another important entity of encephalomyelitis is acute disseminated encephalomyelitis (ADEM). This is an inflammatory demyelinating immune-mediated disorder that usually will erupt in childhood [36]. There is a strong association between ADEM and infectious process or after vaccine administration. It is believed that the reactive immune response of the body leads to pathologic transient autoimmune response directed at myelin or other self-antigens in the CNS [36,37,38,39]. The medical treatment of ADEM is mainly high dose corticosteroids with a good prognosis as more than 50% achieve full recovery. Still, mortality is up to 12%, and refractory elevated ICP is the cause of most cases.

In cases of encephalitis or encephalomyelitis, when elevated ICP symptoms are suspected, there is a need to consider ICP monitoring and CPP management. Yet, clear management guidelines are missing, and the benefit of ICP measurement and surgical intervention is controversial when managing severe herpes encephalitis [40]. Furthermore, the management paradigm for encephalitis is related to ICP monitoring and ICP management from the traumatic brain injury (TBI) literature, which is a different etiology. As with the other entities with elevated ICP, the treatment should progress gradually with accurate monitoring of ICP in cases where there is no reliable neurological assessment. Several groups tried to describe a decision-making mechanism to identify the children with potential elevated intracranial pressure before devastating result happen. In 2020, Kostenniemi et al. published their scale of MeningiSSS (Meningitis Swedish Survival Score) trying to predict those that will benefit from strict monitoring of their ICP [41,42,43,44]. They compared the results of their scale to different known scales and were focused at the presence of altered mental status and leukopenia and circulatory distress, and found it useful in identifying children later having to undergo invasive procedures to monitor or manage their ICP as a result of bacterial meningitis [41].

Medical management of increased ICP includes different methods for relieving intracranial pressure and preserve tissue oxygenation and blood supply [35]. Treatments, such as hyperventilation, osmotherapy, corticosteroids, barbiturate coma, and induced hypothermia, were described in previous reviews, and the overall management is similar to TBI management. Corticosteroids are being widely used in different neurological and neurosurgical entities to reduce cerebral edema. Their use in infectious disease is questionable because of the possible increased viral or bacterial load under steroidal treatment [45]. Most authors advocate for their use in a delayed fashion after initiation of the anti-viral/bacterial treatment [45,46,47]. Hyperosmolar treatment is very widely practiced in the setting of elevated ICP in trauma as well as for elevated ICP due to infectious derived etiologies. Barbiturate coma is a medical therapy that is used for lowering cerebral metabolic demand, which leads to less blood influx to the brain and hence to a reduction in the intracranial pressure [35]. This therapy should be initiated after the failure of the previous tiers or the initial case was extremely severe demanding use of early radical measures. Barbiturate coma requires continuous EEG monitoring (to achieve burst suppression) as well as hemodynamic monitoring due to significant hypotensive crisis risk. In infectious diseases, several descriptions are supporting the early use of barbiturates coma in severe cases [48, 49]. The use of hypothermia has been debated for the last decade, especially in the pediatric population. Yet, as for now although the mechanism has been postulated in few publications it cannot be advocated.

Surgical treatment in elevated ICP derived from infectious disease etiology is scarce. In the pediatric population, it is mainly anecdotal and focused on previously published case reports. Yet, it has been described in the adult population [50]. Several publications advocate the use of decompressive craniectomy leading to high GOS of 4–5. Decompressive craniectomy was shown to be a significant and effective treatment methodology in patients with significant mass effect secondary to encephalitis that failed other treatments [20, 35]. Yet, cases need to be selected carefully since although functional outcome results after decompressive craniectomy look promising, there is not enough evidence to recommend the routine use of this tool in the setting of encephalitis [35]. In case the diagnosis is of a brain abscess the treatment paradigm usually involves tissue diagnosis with or without mass reduction or complete removal of the abscess followed with broad-spectrum antibiotics that will be narrowed according to microbiology answers.

Stroke—malignant MCA, others

Pediatric ischemic stroke is a devastating disease with significant mortality and morbidity. According to different publications, the mortality rate 1 month after severe pediatric stroke is around 12%, and most of the survivors will have significant neurological deficits[51,52,53]. The annual incidence of pediatric stroke differentiates according to etiology, with acute ischemic and hemorrhagic stroke being the most common (1–5 for hemorrhagic stroke and 2–13/100.000 children for ischemic stroke), while cerebral venous thrombosis (CVT) is the least common as possible etiology (0.5–1.0 for every 100,000 children) [54,55,56]. Pediatric stroke is usually ischemic rather than hemorrhagic. The treatment in pediatric stroke derived mainly from the adult literature but had come to the establishment of the treatment paradigm that suggests the identification of the etiology, possible acute intervention, and mainly the prevention of further progression by diminution brain metabolic demands (prevention of drop in oxygen saturation, hyperthermia, hypo- or hyperglycemia, hypo- or hypertension, seizures, infections, etc.) [57]. Large ischemic stroke can lead to a significant increase in the ICP, which might lead to brain herniation, and significant morbidity, and even mortality [51]. Decompressive hemicraniectomy (DC) was shown already in several publications to be an important and significant treatment modality to achieve immediate reduction for the rapid rise in ICP and is known to reduce mortality and improving outcomes among adult patients with malignant stroke [58]. Yet, the use of this radical tool is preserved for cases in which more conservative methods, including osmolar treatment, prevention of hyperglycemia and fever, and even barbiturate coma, failed to relieve the elevated ICP. The devastating numbers of mortality and morbidity were the driving force behind the randomized controlled trials (RCTs) DECIMAL, DESTINY, and HAMLET. These trials showed that the use of DC can significantly reduce mortality (case fatality reduction closely estimated as 50–75%) without increasing the risk for severe functional outcomes. The results were for patients under the age of 60 years and that was operated on for decompressive craniectomy within 48 h from the stroke [58, 59]. Most stroke patients will not develop the devastating elevation of ICP mandate treatment. In the special setting of large MCA (Middle cerebral artery) stroke, there is the potential of developing malignant MCA syndrome, which is a life-threatening event because of acute elevation of intracranial pressure and brain herniation secondary to the development of severe brain swelling. The incidence of malignant MCA stroke in the pediatric population is much smaller in comparison to adults (2% vs. 10%) [60]. The use of ICP monitoring is less common among these patients and the treatment decision is usually derived from clinical status and imaging [61]. Yet, in cases of more aggressive treatment like barbiturate come, ICP measurement might become significant for decision-making to anticipate the need for DC. The American Heart Association guideline for the early management of adults with ischemic stroke recommends DC as a lifesaving measurement in cases of severe malignant stroke. As mentioned above, DC in the right cases within 48 h will decrease mortality and can assist in preventing further neurological deterioration [58, 62,63,64,65]. The use of DC in pediatric ischemic stroke has become more common in recent years with acknowledgment of its benefits for the adult population. There is no clear evidence regarding when DC should be done in case malignant stroke develops. Delay in utilizing DC can lead to a worse prognosis and in some cases to hemorrhagic conversion [66]. When considering all recent data, including the recent data suggesting that the use of barbiturate come is as relevant as DC for intractable elevated ICP in face of the outcome of both treatments, we can summarize that only when maximal medical management of ICP has failed, the use of DC should be considered in children suffering from a pediatric stroke [67].

Sinus venous thrombus—spontaneous, trauma-related

Cerebral sinus vein thrombosis (CSVT) is a known phenomenon that can happen in a variety of clinical statuses. The brain vasculature system allows the blood to be drained through the different venous sinuses. In case one of the major sinuses is occluded, there is a steep rise in ICP due to lack of blood drainage from the brain. CSVT and arterial stroke differ for both the clinical evolution as well as the natural history [68]. CSVT accounts for 0.5% of all stroke cases [69]. The respective incidence in children and neonates is higher than in adults [70,71,72]. Most of the cases will involve either the superior sagittal sinus (SSS) or transverse sinus (TS). Etiologies may vary widely. The most common causes are prothrombotic states, either genetically imposed or acquired. Other pathologies include malignancy, hematological pathologies, inflammatory systemic disorders, postoperative related, infections (i.e. mastoiditis), trauma, jugular vein catheterization, and more [73,74,75,76]. Recent publication focused on the risk factors for CSVT among pediatric patients found that in a multivariant analysis head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for the development of pediatric CSVT [72].

The management paradigm includes diagnosis by imaging, usually either MRI with a specific focus on venous system (MRV), CTV, or even venography (Fig. 1). The treatment goal is to stop the progression of the thrombotic event as well as understanding the causative etiology. In cases where there is altered mental status and suspected elevated ICP, urgent steps are taken to control ICP, measure it, and actively lowering it [77]. In 2008 and later in 2011, several important manuscripts were published with the recommended use of anticoagulation for children [78,79,80,81].

Fig. 1
figure 1

Transverse sinus thrombosis. Sinus vein thrombosis can be seen in regular CT scan as hyper density (a) around the sinus (as a result of blood stasis), and as a filling defect in CT venogram (b)

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ICP management in the setting of sinus vein thrombosis includes several treatment options, such as acetazolamide administration, external ventricular drainage (that allows ICP monitoring as well as an effective treatment to lower excessive pressure), CSF shunt insertion, or even DC [68]. Decompressive craniectomy was found to be effective for CSVT when there is large parenchymal hemorrhage, or an acute mass effect secondary to cerebral swelling and failure of conservative treatment for decreasing intracranial pressure [82]. The use of thrombectomy either endovascular or surgical has been an issue for debate in recent years. Some centers advocate the use of endovascular treatment first when the patient starts to have neurological deterioration or have significant findings in imaging and conservative treatment failed [83]. Yet, when taking the published data that we have today, in cases where the pressure is building up within the brain in a more diffuse pattern, a better treatment paradigm will be measuring neurological status and ICP when needed, use of mannitol or hypertonic saline, and even barbiturate coma. DC in these cases should be the last result [84, 85].

Idiopathic primary increased ICP

Idiopathic intracranial hypertension (IIH) is diagnosed in patients with elevated intracranial pressure with normal brain parenchyma and small ventricles that lack an identifiable cause for elevated pressure. IIH is seen predominantly in young women of childbearing age and among obese girls, however, it can be seen across all ages, genders, a wide range of body mass indices (BMI), ethnicities, and socioeconomic statuses. The pathophysiology of IIH remains uncertain.

Incidence of IIH in pediatrics has been difficult to estimate given the paucity of appropriate studies in this population. It has been reported that 37% of all cases of IIH are children, and 90% of these are between the ages of 5–15 years old [86]. Previous studies found the incidence of primary intracranial hypertension (PIH) to be 0.47–1.2 per 100,000 children, higher than that of secondary intracranial hypertension (SIH), which was 0.32 per 100,000 children [87,88,89].

The presentation of patients with PIH varies with age. It is harder to diagnose in younger children due to more subtle symptoms and the ability to communicate their symptoms [90]. The most common presenting symptom and the most consistent symptom is headaches, which is present in 30–96.5% of patients [91,92,93]. Headaches are described as worse in the morning and can be exacerbated by straining, coughing, Valsalva, and bending down. Visual changes are the second most common symptom and are present in > 70% of patients [91]. Yet, bilateral papilledema or optic disc swelling is the most common finding on an exam with a frequency of 87% in children [94]. In pre-pubertal children, incidentally found bilateral papilledema is common and it has been reported in as high as 33% of the cases in the literature. However, papilledema is not identified in every patient and although it is often found bilaterally, it can also be seen unilaterally. If papilledema is left untreated, it can lead to sudden or gradual blindness as the increased pressure causes circumferential compression of the retinal ganglion cells in the optic nerve [86]. Visual field cuts are seen in 74–85% of patients on presentation and the most common defect is an enlarged blind spot [92, 95, 96]. Transient visual obscurations (TVO) described as blacking out of the vision for approximately one second are also widely reported and tend to be exacerbated by either straining, Valsalva, bending, etc. Blurry vision is a very common, however, nonspecific complaint. Diplopia has been reported in 16–42.3% of patients [90, 93, 97]. Unilateral abducens palsy can present as esotropia and diplopia when looking towards the side of the affected eye. In the literature, cranial nerve VI palsies have been reported as low as 12% of patients and as high as 60% of cases [91, 93, 98, 99]. Tinnitus is also a common symptom seen in 40–50% of patients and is often pulsatile and unilateral [90, 91]. Other symptoms of increased intracranial pressure are also seen, and in rare cases, even spontaneous CSF leak can be the presenting symptom [92, 96, 98]. It is important to note that the symptoms can be similar to those caused by posterior fossa lesions including but not limited to cranial nerve VII palsy, ataxia, nuchal rigidity, Babinski sign [100].

The latest criteria include (1) signs and symptoms of elevated intracranial pressure as discussed above, (2) lack of focal neurologic deficits (excluding cranial nerve IV and VI palsies), (3) normal CSF studies, (4) CSF opening pressure of > 18 cm H20 in children < 8 years old or > 25 cm H20 in children > 8 years old or < 8 years old without optic nerve edema, and (5) normal or small ventricles [89].

Diagnostic studies consist of MRI to rule out a mass lesion and a lumbar puncture for opening pressure (OP) and CSF studies. This is important to note in infants that have open sutures, as the increased ICP may lead to an increasing head circumference and a bulging fontanelle, but not papilledema [100]. Magnetic resonance venography (MRV) is the test of choice to rule out venous sinus thrombosis and is especially necessary for atypical patients, atypical presentations, patients with recent infections in sinuses or ears, patients refractory to routine medical treatment, and patients with a more sudden presentation. MRV has also been recommended in children as these are considered atypical patients and data shows 11% of cases are positive for venous sinus thrombosis [100, 101].

Imaging studies should reveal normal brain parenchyma and normal to small ventricles. Findings that are common in patients with intracranial hypertension include slit-like ventricles, empty sella, protrusion of the optic nerve head anteriorly, flattening of the posterior globe, dilatation of the optic nerve sheath, abnormal appearance of the optic nerve through its orbital portion, enhancement of the posterior sclera (Fig. 2) [95, 102, 103]. Presence of these findings assists in diagnosis, but their absence does not rule out IIH.

Fig. 2
figure 2

Idiopathic intracranial pressure. Previously known as pseudotumor cerebri, this entity by definition should be without any intracranial etiology that can result in mass effect. One of the signs being used in recent years is the T2 changes in the optic nerve sheath (a—axial, b—coronal), as a sign for intracranial pressure and builds up of papillary edema

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A lumbar puncture (LP) serves as a diagnostic test, may provide patients with temporary relief of symptoms caused by elevated ICP, and it also assists in treatment decisions as by removing some CSF it demonstrates whether CSF diversion would be effective. However, it is important to note that the patient’s response to the LP is not diagnostic of IIH. The pressure would return to what it was prior to LP within 1–2 h [104, 105]. In equivocal cases, the intracranial pressure can be monitored for an extended period via lumbar drain or intracranial pressure monitor.

Treatment for IIH should be designed by a multidisciplinary team involving a primary care doctor, a neurologist, a dietitian, an ophthalmologist, and if there is an ultimate need for surgical intervention, neurosurgery. The main reason to treat IIH is to prevent blindness and to provide pain relief. The first line of treatment is medical management. In patients who are overweight, this consists of first and foremost a weight loss plan. It has been shown that weight loss of as little as 6% body weight can result in resolution of papilledema [106]. Alternatives for weight loss include diet, exercise, and in adults, it may include surgical interventions like laparoscopic banding and gastric bypass.

Acetazolamide is the first-line medication for IIH in both adults and children. Acetazolamide is a carbonic anhydrase inhibitor that leads to decreased CSF production [107]. If acetazolamide is not effective, other possible medications are furosemide and methazolamide. Furosemide can be used alone or with acetazolamide as a synergistic effect has been reported. It is important to note the possible side effects of these medications. Acetazolamide can lead to a metallic taste and furosemide to hypokalemia. Given the need to monitor potassium levels and replace potassium accordingly, furosemide is considered a second-line medication when treating children [108]. Topiramate and methazolamide are both weak carbonic anhydrase inhibitors used as well. Octreotide can be used in adults, however, in children, it is not recommended given that it inhibits growth hormone and IGF-1 [109]. Lastly, corticosteroids can be used in combination with acetazolamide in cases of sudden rapid visual decline [90].

Surgical interventions are indicated if medical management fails if a patient does not tolerate medical management, if papilledema is severe, or if vision loss is rapidly progressing as weight loss and medications take some time to work [90]. Options for surgical interventions include (1) CSF diversion via ventriculoperitoneal shunt (VPS) or lumbar-peritoneal shunt (LPS) placement and (2) optic nerve sheath fenestration (ONSF). Serial lumbar punctures are advocate by some as spontaneous remissions are common within months to a year of onset. Surgeries like subtemporal or suboccipital decompressions are not in the frontline of the surgical armamentarium and are used rarely.

CSF diversion is ideal for patients that complain of headaches as their primary symptom. Shunting decreases intracranial pressure and helps relieve both headaches and papilledema. Debate still exists regarding what type of shunt is better for patients with IIH. Abubaker et al. compared VPS and LPS. The study determined that VPS has a failure rate of 14% and a revision rate of 30% whereas LPS has a failure rate of 11% and a revision rate of 60% [110].

Patients should be followed for at least 2 years with serial imaging to rule out any obscure, developing, or difficult to diagnose the secondary cause of intracranial hypertension [86]. Outcome data are scarce for the pediatric population. 43–68% of adult patients describe a persistent, yet different headache after treatment [100]. Papilledema does not resolve in about 15% of patients [86]. Permanent visual loss is reported in 2–24% of patients in the literature [86]. Estimates for recurrence are around 18–20%, but a relationship between BMI and risk of recurrence has not been identified [111].

Craniosynostosis

Craniosynostosis is a condition that is diagnosed whenever there is premature closure of one or more of the skull sutures. Incidence has been reported as 1 in 2000–2500 live births [112]. Craniosynostosis is classified by the specific suture or sutures involved, and it can be syndromic or nonsyndromic, with 80–90% of hospitalized children having the nonsyndromic subtype [112, 113]. Craniosynostosis can lead to increased ICP, especially in syndromic craniosynostosis cases. In this subgroup, increased ICP has been reported in 30–50% of cases [114]. Elevated ICP is more common in patients with multiple sutures that are prematurely fused than in patients with single fused sutures [115]. However, elevated ICP has been reported in 11–14% of cases with a single fused suture [114]. Craniofacial dysmorphic syndromes are typically associated with the fusion of multiple sutures and special care has to be taken when evaluating these patients for interventions as their risk for increased ICP is higher than single suture craniosynostosis (i.e. Crouzon, Apert, Pfeiffer, Kleeblattschädel syndromes, amongst others).

Increases in ICP can lead to abnormal development of the brain with significant consequences for these children [116]. An older study identified that for the first 6 years of life, ICP increased with age [115, 116]. ICP monitoring has been studied in patients with craniosynostosis and it can be used to diagnose elevated ICP and make treatment decisions regarding surgical intervention and timing of surgery if determined necessary. The threshold for elevated ICP differs across the literature and across age groups, which limits the generalization of study results for guidelines and the application of these results in general practice. The most common parameters in the literature are as follows: ICP is normal if it is < 10 mmHg, ICP is borderline if it measures 10–15 mmHg, and ICP is considered elevated if > 15 mmHg [115, 117,118,119]. Yet others suggested that a more sensitive way of diagnosing patients with elevated ICP is to calculate the frequency of ICP elevations > 20 mmHg, rather than making the diagnosis based on the calculated mean ICP [120].

The expected findings of increased ICP and imaging reflective of increased ICP are not common in patients with craniosynostosis [114, 118]. Possible symptoms of increased ICP in these patients are persistent headaches, sleep disturbance, irritability, nausea, deteriorating attention span or academic performance, mental delay [120]; however, these cognitive declines and mental delay findings are wildly debated in the literature as to their association with increased ICP and the long-term effects of ICP elevations on function and development in the presence of other factors that can lead to these same developmental issues [116]. Papilledema is not commonly identified in young children with non-syndromic craniosynostosis and raised ICP [118, 121]. On imaging, one can see decreased subarachnoid spaces, sulcal effacement, beaten copper appearance of the calvarium with a sensitivity of 82% and specificity of 27% [118]. Tuite et al. studied 123 patients with craniosynostosis focusing on imaging findings and ICP [119]. Certain imaging patterns were found to be normal in different age groups and not others. They identified that in children < 18 months old diffuse beaten copper patterns, effacement of the basal cisterns or the sulci were strong predicting factors for the presence of elevated ICP [122]. It is crucial to note that those findings did not predict elevated ICP in older children, as they are seen in these patients even in the presence of normal ICP. Hydrocephalus was the most sensitive indicator of elevated ICP when accounting for all patients; however, they found that hydrocephalus only detected 40% of patients with elevated ICP. They noted that suture diastasis and dorsum sella erosion had a specificity of at least 90% for elevated ICP [119]. When analyzing imaging findings for patients with craniosynostosis, age is a very important factor that assists in determining the relevance of any findings and whether it will change the treatment plan.

The gold standard to diagnose elevated ICP is invasive monitor placement. ICP monitoring is indicated for children who present with persistent symptoms of increased ICP in the absence of any objective symptoms on imaging or ophthalmologic evaluation [117].

Surgery for correction of craniosynostosis is only necessary in about 20% of cases [86]. Most children with mild craniosynostosis do not show significant symptoms, even in the presence of elevated ICP. In the presence of elevated ICP, early surgery is indicated for cranial vault expansion (for kids with fused sutures). Cranial vault expansion has been shown to relieve symptoms of increased ICP [123].

Chiari malformation

A Chiari malformation is characterized typically by a hindbrain abnormality and CSF flow disturbance. There are several types, from Chiari 0–Chiari IV; however, they do not relate to each other embryologically [124]. Treatment via posterior fossa decompression relieves symptoms and reduction in the size of the syrinx [125]. A Chiari I malformation, or simply a Chiari malformation, is the most common type and it is defined by elongated “pegged” cerebellar tonsils with > 5 mm of tonsillar herniation through the foramen magnum in a way that creates compaction of the foramen magnum. It presents later in life than the other types, typically in adulthood during the second or third decade of life [124, 126]. The most common presenting symptoms are pain, most commonly suboccipital pressure-like headaches (81% of cases) exacerbated by straining, physical activity, Valsalva, and bending down [126]. Chiari, I malformation is associated with syringomyelia in 20–85% of cases [124, 127, 128]. The alterations of CSF flow in these patients are believed to cause the syrinx.

The surgical intervention in Chiari malformation is intended to decompress the posterior fossa and brainstem and reestablish CSF flow. Surgery includes a suboccipital decompression and depending on the case, a cervical laminectomy, duraplasty, and tonsillar shrinking. Asymptomatic patients do not require treatment.

The need for CSF diversion in those patients that underwent decompression surgery is not clear. The previous publication found a significant abnormal pulsatile pressure gradient between the intracranial and lumbar compartments, which is even worse in patients with a syrinx [129]. Yet, the second intervention for CSF diversion after decompression surgery is rare [130].

Acquired Chiari, I malformations can occur when there is a significant gradient between the intracranial and cervical compartments. This can occur in the setting of over drainage from a lumboperitoneal shunt or in patients with CSF leaks. Patients with hydrocephalus or idiopathic intracranial hypertension can also develop downward herniation of tonsils and an acquired Chiari I malformation [128].

Hydrocephalus

Hydrocephalus is a well-known pathology in the pediatric population. Many etiologies can lead to hydrocephalus among the pediatric population. A full discussion of this topic is beyond the scope of this review.

Conclusion

Increased intracranial pressure is a potentially devastating process, especially in the young population. Different etiologies can lead to increased pressure due to brain edema, mass effect, or obstructive hydrocephalus. When clinical signs and symptoms suggesting the rise of intracranial pressure are present, urgent measures need to be taken to preserve cerebral tissue perfusion, oxygenation, and hence brain function.

Summary

  • The gold standard to diagnose elevated ICP is invasive monitor placement

  • The treatment is a tier-based treatment similar to the traumatic brain injury guidelines

  • For Herpes simplex encephalitis, acyclovir therapy dramatically reduces mortality, and around half of the patients return to normal function.

  • Some studies are supporting the utility of decompressive craniotomy in severe encephalitis, but true evidence is lacking.

  • For adults with malignant stroke, decompressive hemicraniectomy is an effective and recommended treatment for elevated ICP that failed conservative treatment, which can reduce mortality and improve functional outcome. It is recommended to consider the same treatment methodology in the pediatric population, although the lack of age-specific data.

  • For patients with CSVT, decompressive craniectomy should be considered in the presence of large mass effect (e.g., intracerebral hemorrhage or malignant cerebral edema) with signs for decompensation (pending herniation).

  • For idiopathic intracranial hypertension, surgical interventions are only indicated if medical management fails, if a patient does not tolerate medical management, if papilledema is severe, or if vision loss is rapidly progressing as weight loss and medications take some time to work.