How Quickly Does Papilledema Manifest In Intracranial Hypertension?

Introduction

Papilledema, or optic nerve edema secondary to increased intracranial pressure, is a well-established sign of increased intracranial pressure. Determining whether or not the intracranial pressure is actually high is important, especially in acute cases such as head trauma and intracranial bleeding. It’s difficult to determine intracranial pressure; even invasive measurements such as lumbar punctures or epidural probes are not always accurate.

Ophthalmologists are often asked to consult on these types of problems, whether it’s an acute-onset headache, suspected intracranial abnormality such as pituitary apoplexy, ruptured aneurysm, closed head trauma, patency of a previous neurosurgical shunt in the setting of an acute headache, etc. The workup typically involves some combination of the following:

  • Neuroimaging (CT or MRI series)

  • Dilated funduscopic exam (to look for papilledema)

  • Color photography of the optic disc

  • Fluorescein angiography of the fundus

  • Lumbar puncture

Because clinical decision-making for intervention is often based off of non-invasive diagnostic testing only, it’s helpful to know how long it takes for papilledema to develop in acute intracranial hypertension.

What The Research Says

Studies in Rhesus Monkeys

Hayreh et al (1977)

In 1977, Hayreh et al published a series of articles detailing their experiments with rhesus monkeys and the development of papilledema following acute elevation of intracranial pressure (ICP) (1-4).

  • The elevated ICP was induced by an inflatable balloon in the temporal subarachnoid space.

  • The optic disc was observed by direct ophthalmoscopy, color stereoscopic photography, and stereoscopic fluorescein angiography.

Their findings contributed greatly to our understanding the pathologic development of papilledema, as well as a general time course for development. Hayreh’s research found that papilledema developed typically developed within the first 5 days of acute ICP elevation in monkeys:

  • 30% developed papilledema within 1 day

  • 50% developed papilledema within 2 days

  • 90% developed papilledema within 5 days

Hayreh’s studies also suggested that color fundus photography with fluorescein angiography was more accurate in detecting mild elevation of the optic disc than direct ophthalmoscopy (2).

Criticisms:

  • How intracranial pressure is elevated in humans may vary from the artificially-induced mechanism in Hayreh’s studies (5).

  • The results of how soon papilledema develops after acute elevation of ICP has not been as reliably reproduced in humans (5-6).

  • Hayreh’s recommendation of utilizing fundus photography with fluorescein angiography over direct ophthalmoscopy may not be practical in an emergency setting (5).

Studies in Humans

Fahmy (1972)

Fahmy reported on a series of 195 patients with ruptured intracranial aneurysms diagnosed intraoperatively, at autopsy, or both (7).

  • Only 32/195 patients (16%) reportedly had papilledema (the description and diagnostic criteria used for determining papilledema was not defined).

  • Only 8 patients were examined a few hours after the rupture; of those 8 patients, 3 patients developed hyperemia of the optic nerve.

  • A few patients (7/195) were described to have unilateral papilledema.

Though this report is not without its criticism (lack of stated criteria for diagnosis of papilledema, high degree of variation between time of rupture and time of examination, etc.), this series of cases would suggest that a ruptured aneurysm does not commonly result in papilledema, and as such a normal dilated funduscopic examination does not rule out a ruptured aneurysm.

Steffen et al (1996)

in 1996, Steffen et al investigated 37 patients with acute elevation of intracranial pressure (ICP) from intracranial hemorrhage or head trauma and followed fundus examination by direct and indirect ophthalmoscopy every 12-24 hours for at least 7 consecutive days to determine the onset of papilledema in these patients (5). Friedman noted that this is the largest study that set out to investigate the onset of papilledema in the setting of acute raised intracranial pressure (6).

  • In patients with mildly elevated ICP (20-30 mmHg over 3 consecutive days), no patients developed papilledema (0/13), and only 2 patients had venous congestion by day 6.

  • In patients with ICP of 30-70 mmHg over 3 consecutive days, only 1 patient developed papilledema (1/7); this patient developed fatal cerebral edema and carotid artery distribution infarction postoperatively.

  • The remaining 17 patients had transient elevations of ICP between 20-60 mmHg less than 3 days, and none of them (0/17) had papilledema.

This study concluded that acute rises in intracranial pressure do not always cause immediate papilledema and in fact may be rare. This further supports the implication that a normal fundus examination in the setting of suspected acute intracranial hypertension does not exclude increased intracranial pressure.

Take Home Points

  • The presence of papilledema may be a helpful noninvasive method of qualitatively measuring the presence of increased intracranial pressure.

  • However, in acute settings, a normal-appearing optic disc does not exclude increased intracranial pressure. While it is certainly possible and has been reported in several situations that papilledema can present rapidly in acute intracranial hypertension, it should not be considered the gold standard for determining whether or not there is increased ICP (8).

So this information got me thinking about a few common clinical scenarios and how I might manage them based on these findings:

Consult #1: Acute-Onset Headache, Rule Out Ruptured Aneurysm

Patients who present with the dreaded “worst headache of my life” complaint should rightly concern us about some sort of intracranial hemorrhage. As an ophthalmologist and neuro-ophthalmologist, we are trained (correctly) to hear those complaints and quickly perform a funduscopic examination to look for papilledema.

But what if the optic nerves look flat? Well, based on these articles, I think it means that the funduscopic examination really does not provide much helpful data if there is a strong enough concern for intracranial hemorrhage, whether from a ruptured aneurysm, pituitary apoplexy, or other modality. Therefore, don’t delay further diagnostic testing (such as a CT, MRI, or LP) waiting for a dilated funduscopic examination - because if you see papilledema, then you’re going to act, and if you don’t see papilledema, you’re still going to have to act. The optic nerve appearance has no significant effect on the overall clinical decision-making.

Consult #2: Closed Head Trauma, Rule Out Intracranial Hemorrhage

In this scenario, I am imagining a patient who is potentially intubated/sedated in the ICU, unresponsive due to a severe head trauma. A dilated funduscopic exam may be helpful, as papilledema may be a helpful sign to suggest further intervention…but should the absence of papilledema reassure us to observe only? These articles suggest that perhaps this might not be the case - and in fact, there could still be raised intracranial pressure even with normal optic nerves.

So What?

As an ophthalmologist (or neuro-ophthalmologist) who may be asked to perform a dilated funduscopic examination on these patients, it seems like it’s important to stress to the referring providers (both in your documentation and in any verbal communication) that even with a normal optic nerve, the intracranial pressure may still be high, and that if the clinical suspicion for elevated pressure is great enough, further testing (especially more invasive measures) may be necessary to protect the brain from potential harm.

References

  1. Hayreh MS, Hayreh SS. Optic disc edema in raised intracranial pressure: I. Evolution and resolution. Arch Ophthalmol 1977;95:1237-1244.

  2. Hayreh SS, Hayreh MS. Optic disc edema in raised intracranial pressure: II. Early detection with fluorescein angiography and stereoscopic colour photography. Arch Ophthalmol 1977;95:1245-1254.

  3. Hayreh SS. Optic disc edema in raised intracranial pressure: V. Pathogenesis. Arch Ophthalmol 1977;95:1553-1565.

  4. Hayreh SS. Optic disc edema in raised intracranial pressure: VI. Associated visual disturbances and their pathogenesis. Arch Ophthalmol 1977;95:1566-1579.

  5. Steffen H, Eifert B, Aschoff A, et al. The diagnostic value of optic disc evaluation in acute elevated intracranial pressure. Ophthalmology 1996;103:1229-1232.

  6. Friedman DI. Papilledema. In: Miller NR, et al. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. 6th Edition. Philadelphia; Lippincott Williams & Wilkins, 2005: 255.

  7. Fahmy JA. Papilloedema associated with ruptured aneurysms. Acta Ophthalmol 1972;50:793-802.

  8. Pagani LF. The rapid appearance of papilledema. J Neurosurg 1969;30:247-249.