Increased Intracranial Pressure

Abstract

Intracranial hypertension has gone by numerous different terms over the years. Symptoms of intracranial hypertension include a headache that can be exacerbated by maneuvers such as Valsalva, bending over or coughing. Other symptoms include nausea, vomiting, diplopia, cranial nerve palsy, and tinnitus. The ophthalmic exam is a fundamental part of the diagnosis and management of intracranial hypertension. A direct funduscopic exam of the optic nerves should be performed at each visit. Diagnostic neuroimaging should include MRI and MRV to rule out secondary causes. The largest diagnostic component is the lumbar puncture. Proper positioning includes lateral decubitus with the legs and heads extended at the time of measurement. Weight loss (if obese) and acetazolamide are considered the first-line treatment for intracranial hypertension. Recurrence is estimated to occur in up to 20% of patients. The development of migraine or other headache syndromes is seen in up to 68% following resolution of their intracranial hypertension.

History

The original description of intracranial hypertension has been credited to Heinrich Quincke, who pioneered the lumbar puncture. In 1897, he described a series of patients suffering from increased intracranial pressure with normal cerebral spinal fluid (CSF) and labeled this condition “meningitis serosa”.¹ Since Quincke’s initial description, there have been many different names used including serous meningitis, otitis hydrocephalus, toxic hydrocephalus, and hypertensive meningeal hydrops. In 1904, the term “pseudotumor cerebri” was coined by Nonne after similarities in a presentation to patients with an intracranial mass.² In 1955, Foley suggested “benign intracranial hypertension” to remedy the negative association with a “pseudo-cancer” diagnosis.³ The term idiopathic intracranial hypertension appeared in the 1980s following a series of reports describing permanent visual deficits.

Today, pseudotumor cerebri and idiopathic intracranial hypertension remain the most common terminology amongst both practitioners and the lay public. There remains both ambiguity and confusion with both of these terms. There have been recent attempts to clarify the terminology with some using a broader designation of “pseudotumor cerebri syndrome” which still includes the designation of idiopathic when a cause is not found.⁴ An easier designation is the use of the terms primary intracranial hypertension (PIH) and secondary intracranial hypertension (SIH).⁵ The designation of the primary would apply when no precipitant that would result in increased pressure is present. Patients may still have risk factors for increased intracranial pressure, such as female gender, post-pubertal status, obesity, or polycystic ovarian syndrome, though these conditions do not directly result in increased pressure. SIH is then reserved for instances where the intracranial hypertension is the direct result of another condition, such as cerebral sinus venous thrombosis, or minocycline use.

PIH has traditionally been considered a rare entity. The annual incidence in adults residing in the United States is estimated at 0.9 per 100,000, with no good estimates in the pediatric population.⁶ The annual pediatric incidence is estimated at 0.47 and 1.2 per 100,000 in Germany and Croatia respectively.^7,8 In the provinces of Nova Scotia and Prince Edward Island, the annual incidence was 0.9 per 100,000 in children 2 to 15 years old between 1979 and 1994.⁹ Interestingly from 1997 to 2007, the annual incidence fell to 0.6 per 100,000 in children 2 to 16 years, despite increased childhood obesity during this period.¹⁰

Diagnostic Criteria

The diagnostic criteria for adult PIH were developed from a series of 22 patients reported by Dandy in 1937.¹¹ The main limitation of this set of criteria is that imaging of the time was limited to pneumoencephalograms. In 1985, Smith proposed modernization of the criteria into what is now accepted as the modified Dandy criteria to include more current imaging criteria. The criteria stipulate that patients have: 1) signs and symptoms of raised intracranial pressure (headache, nausea, vomiting, transient visual obscurations, or papilledema), 2) absence of localizing neurologic signs with the exception of unilateral or bilateral abducens nerve palsy, 3) CSF opening pressure of >25 cm H20 with normal composition, 4) normal to small ventricles as demonstrated by computed tomography (CT) study (today magnetic resonance imaging (MRI)).¹²

Secondary Intracranial Hypertension

Numerous medications have been reported to lead to SIH. The most widely known is the tetracycline class of medications, including tetracycline, minocycline and doxycycline.^17-19 Chronic corticosteroid use can result in increased pressure following weight gain from chronic use, but also with acute withdrawal or rapid wean.

Patients being treated with recombinant growth hormones can develop symptoms of intracranial hypertension including headache and optic nerve edema.^{20, 21} The timing from initiation of growth hormone to presentation is often in the first 12 weeks of treatment, though it can occur years after treatment was started.²¹ Treatment includes cessation of the growth hormone and often acetazolamide until symptom resolution. Once symptoms resolve, patients can be restarted on a lower dose of growth hormone with gradual titration without recurrence of symptoms.

Other medications reported in the literature include lithium, nalidixic acid, hypervitaminosis A, hypovitaminosis A, and All-Trans Retinoic Acid, a vitamin A derivative. Oral contraceptives are reported to be associated with SIH, though the association is likely due to CVST from the use of contraceptives.

Cerebral Venous Sinus Thrombosis (CVST) is a common non-medication cause of SIH. Superior sagittal sinus and the transverse sinuses are most often seen (figure 1), though thrombosis of any venous outflow can result in increased pressure. Prior to the widespread use of antibiotics to treat chronic otitis or mastoiditis, patients would develop thrombosis of the sigmoid sinus or jugular vein, formerly referred to as otitic hydrocephalus. Hypercoagulable states such as acute post-partum period, oral contraceptive use, cancer (lymphoma/leukemia), and various inherited coagulopathies can also result in CVST.

The initiation of feeding in cases of poor nutrition from starvation or malabsorption syndromes has resulted in a transient increase in intracranial pressure.^22,23 Often a bulging of the anterior fontanel is the only symptom in infants. Older children may develop irritability and cranial suture separation. Fortunately, in most cases, it is a transient process that self resolves within a few days to weeks.

Figure 1. Superior sagittal sinus thrombosis (large arrows) and transverse sinus thrombosis (small arrow).

Common Causes of Secondary Intracranial Hypertension

• Medications
• Minocycline / Tetracycline / Doxycycline
• Corticosteroids (especially withdrawal)
• Growth hormone
• Lithium carbonate
• Cyclosporine A
• Cytarabine
• Nalidixic acid
• Retinoic acid
• Vitamin A (excess or deficiency)
• Vitamin D

• Medical conditions

  • Cerebral venous thrombosis
  • Refeeding syndrome
  • Adrenal insufficiency (often on steroids)
  • Congestive heart failure
  • Hypoparathyroidism (early in correction)
  • Pregnancy/eclampsia
  • Crohn’s disease
  • Meningitis/encephalitis
  • Intracranial hemorrhage
  • Lyme disease
  • Demyelinating disease / multiple sclerosis
  • Leukemia
  • Lymphoma
  • Hydrocephalus
  • Craniofacial syndrome
  • Chiari Malformation

Presentation

In pediatrics, PIH is typically divided into pre-pubertal and pubertal groups. Pubertal patients have the same risk factors as adults, whereas obesity and gender are not prominent risk factors in pre-pubertal patients. Balcer et al. found that obesity did correlate with an increased risk of PIH in children over 11 years old.¹³ Bursztyn et al. found similar results in those >12 years old.¹⁰

Symptoms of intracranial hypertension tend to be less evident in younger individuals. In the pre-pubertal population, optic disc edema incidentally discovered on routine ophthalmologic examination is seen. Asymptomatic cases are often younger, have a male predominance, and a lower percentage of obesity.¹⁴ Up to 48% of cases lack papilledema, yet have other symptoms consistent with elevated intracranial pressure and documented elevated opening pressure.^7,15,16

The most consistent symptom is a headache that is typically constant with variable severity throughout the day. Headaches tend to be most severe in the morning following prolonged horizontal positioning and may be exacerbated by maneuvers such as Valsalva, bending over, or coughing. Other symptoms include nausea, vomiting, and diplopia.

Cranial nerve VI palsy is the most common nerve palsy with patients complaining of diplopia with the horizontal gaze. Tinnitus is experienced by 10% of pediatric PIH patients and is often unreported until asked.⁸ Patients will report a “whooshing” sound coinciding with their heartbeat.

Papilledema refers to the presence of optic disc edema in the setting of verified increased intracranial pressure. Optic disc edema in absence of increased intracranial pressure can be seen in optic neuritis, neuroretinitis, anterior ischemic optic neuropathy, and infiltration of the optic nerve head by tumor cells. An afferent pupillary defect is rare in intracranial hypertension, and if found should raise concern for the possibility of optic neuritis. Pseudo-papilledema gives the appearance of optic nerve edema to those unfamiliar with the fundus exam (and even the experienced at times). Common culprits are anomalous optic nerves and optic nerve drusen. Unilateral or marked asymmetric edema should raise concern for one of these conditions.