Papilledema as a Marker for Predicting Outcomes in Patients with Moderate Head Injury

Abstract

Introduction Papilledema indicates raised intracranial pressure, which is a significant finding in head injury patients. Being a bedside marker, papilledema can be used for predicting the prognosis in head trauma patients.

Objective The aim of the study was to assess papilledema as a single prognostic marker in moderate head injury adult patients.

Materials and Methods An observational study was done at the Sawai Man Singh Medical College on 120 patients with moderate head injury (Glasgow Coma Scale [GCS] score of 9–12). CT scan and fundoscopy were done in all patients within the first 24 hours and then the patients were followed up for 3 days. Outcomes were noted in terms of Glasgow Outcome Scale (GOS) during a follow-up of 72 hours after admission where a GOS score of 5 was defined as good outcome.

Results Papilledema was present in 25 (20.83%) patients, with early papilledema (<24 hours) in 1 (4.00%) patient and delayed papilledema (up to 72 hours) in 24 (96.00%) patients. Common CT findings were contusions (61.67%), subarachnoid hemorrhage (30.83%), and diffuse axonal injury (2.5%). The GCS score was 9 in 45 (37.50%) patients, 10 in 31 (25.83%) patients, 11 in 30 (25.00%) patients, and 12 in 14 (11.67%) patients at admission. Compared with those without papilledema, patients with papilledema had significantly more contusions (84 vs. 55.79%, p = 0.031). There was a significant association of GCS at 24 hours with papilledema (p < 0.05). Even GOS score showed a significant association with papilledema (p < 0.0001). The absence of papilledema demonstrated sensitivity of 96.87% (95% confidence interval [CI]: 89.16–99.62%) and specificity of 41.07% (95% CI: 28.10–55.02%) with an area under the curve of 0.69 (95% CI: 0.60–0.77) for predicting good outcomes.

Conclusion Papilledema was present in 25 (20.83%) cases of moderate head injury. The absence of papilledema showed 70.83% predictability for good outcomes, showing a significant association with prognostication of patients allowing its usage for monitoring and management of the patients.

Keywords

Glasgow - head injury - outcomes - papilledema

Introduction

Trauma to the brain or traumatic brain injury (TBI) is a significant health concern. The incidence of TBI is reported to be 20.84 million worldwide as reported by the Global Burden of Disease (2021).[1] It is graded as mild to moderate or severe.[2] In comparison to severe head injuries, mild to moderate grade head injuries have better outcomes. But between mild and moderate, assessment of prognostication of moderate head injury patients is being continually done with different techniques as it falls in the borderline injury. Papilledema, also known as edema of the optic disc, is a novel marker, which is indicative of raised intracranial pressure (ICP). Its association has been discussed with head injury and rise in ICP.[3] [4] The incidence of papilledema after TBI is reported to be 51.3% in the study by Mattar et al.[3]

Usually, papilledema is symmetrical and bilateral in TBI. However, cases of unilateral papilledema or asymmetric involvement have also been reported.[5] The relationship between increased ICP and papilledema is governed by the pressure–volume relationship in terms of cerebrospinal fluid volume, increased intracranial pressure, blood–brain barrier, and cerebral perfusion pressure.[6] Whenever there is an increase in the volume of any one of the components, usually it is compensated by other volume, and in case the compensation fails, ICP rises.[6]

Raised ICP in head trauma and papilledema are associated with hemorrhage in the brain like epidural hemorrhage (EDH), subarachnoid hemorrhage (SAH), subdural hemorrhage (SDH), and diffuse axonal injury (DAI).[3]

Papilledema usually occurs immediately after the injury but may be very mild in nature. However, depending upon the severity of injury, it may be intense and may persist and may occur even 1 week after the injury.[2]

The use of papilledema as a bedside novel marker for prognostication of the patients who present with moderate head injury before assessing the ICP can allow for immediate management of the patients and improving the outcomes of the patients. Since head injury and TBI are continually increasing, primarily due to road traffic accidents (RTAs), patients usually present any time during the day with or without the presence of a senior specialist. Attending them initially with the use of a bedside novel marker as papilledema may significantly improve the outcomes of the patients without monitoring of the ICP of the patients.[3]

Thus, the present study was done whereby the primary objective was to determine the presence of papilledema in moderate head injury patients and correlate it with prognosis.

Materials and Methods

An observational study was done at the Sawai Man Singh Medical College (a tertiary care hospital) where 120 patients who presented with moderate head injury. The inclusion criteria were patients with TBI of moderate grade with a Glasgow Coma Scale (GCS) score of 9 to 12. Any patients with anterior fossa fracture and associated with periorbital swelling, edema, or ecchymosis; posttraumatic cranial nerve palsy related to the eyes (e.g., oculomotor nerve palsy) due to disturbed light reflex; and late admission after trauma were excluded.

Sample Size

Mattar et al[3] observed 51.4% of patients had papilledema. Taking this value as reference, the minimum required sample size with a 9% margin of error and 5% level of significance is 119 patients. To reduce the margin of error, the total sample size taken was 120.

Formula used was the following:

where Z_{α /2} = 1.96 at α = 0.05 (95% confidence interval [CI]); p = rate of occurrence of papilledema; q = 1–p; d = allowable error (absolute).

Calculations:

Patients were explained about the study. A written informed consent was taken. Ethical committee clearance was obtained from the hospital before beginning the study. Patients' details were noted in terms of age, gender, symptoms, their GCS at admission,[7] and their Glasgow Outcome Scale (GOS).[8] For examination, the primary investigator investigated the fundoscopy within the first 24 hours along with CT scan of the head. The standard protocol, which was followed in the hospital, was given to all the patients without any changes in the management.

In the fundoscopic examination, the pupil was dilated with one to two drops of mydriatic (tropicamide) 0.5%, 15 to 20 minutes before the examination. These were repeated every 30 minutes. The room was kept dark; the head of the patients was fixed in a position so that the primary investigator could easily do the fundoscopy. If patients had anxiety, sedatives were given. The patients' right eye was examined using a direct ophthalmoscope. The focus field of the ophthalmoscope was adjusted as needed. The ophthalmoscope was directed 15 degrees away from the center where red reflexes were noted until the retina was seen. Then, the examiner pivoted the instrument by angling it upward, downward, left, and right to thoroughly examine the retina. The examiner then switched the ophthalmoscope to the opposite hand to examine the other eye, positioning themselves symmetrically to the temporal side of the patient's other eye, and the process was repeated. All cases were examined by the primary investigator, and observational results were made. Bilateral fundoscopy was done only by a single investigator.

Papilledema was noted as present or absent based on the Frisén scale for papilledema grading. If the optic disc was found to be normal, it was classified as no papilledema. If the optic disc had any degree of edema ranging from minimal, low, moderate, and marked to severe, it was classified as papilledema present. Edema in the optic disc was noted in fundoscopy by the characteristics of the presence of a (1) circumferential halo or (2) elevation of any border that is nasal, superior, or inferior border or (3) disruption of the normal radial nerve fiber layer striations arrangement or (4) obscuration of the major blood vessels leaving the optical disc.[2]

Patients were followed up for 3 days and until discharge. Patients' outcomes were noted in terms of GOS, which was scored from 1 to 5, with 1 indicating death, 5 indicating good recovery, and in-between scores of 2 indicating persistent, vegetative state, 3 indicating severe disability, and 4 indicating moderate disability.[9]

Statistical Analysis

Categorical variables were presented as numbers and percentages, while quantitative data were expressed as means ± standard deviation (SD) and medians with interquartile ranges. Fisher's exact test was used for analyzing qualitative variables. Independent t-test was used to compare the ICP values between two groups. Area under the curve (AUC) was derived for prediction of good outcomes with sensitivity, specificity, and positive and negative predictive values. Data entry was performed in Microsoft Excel, and final analysis was conducted using SPSS software (version 25.0, IBM, Chicago, IL, United States). A p-value of less than 0.05 was considered statistically significant.

Results

Demographic and Clinical Characteristics of Study Patients

The mean age of the patients was 33.76 ± 17.3 years. There were 94 (78.33%) males and 26 (21.67%) females. Loss of consciousness was seen in 116 (96.67%) patients, ear, nose, and throat (ENT) bleed in 72 (60.00%) patients, seizures in 5 (4.17%) patients, vomiting in 102 (85.00%) patients, and others (like fracture, facial injury) in 9 (7.50%) patients ([Table 1]).

Table 1 Parameters distribution

Parameters	n (%)	Mean ± SD	Median (25th–75th percentile)	Range
Gender
Female	26 (21.67)	–	–	–
Male	94 (78.33)
History of loss of consciousness	116 (96.67)	–	–	–
Vomiting	102 (85.00)
ENT bleed	72 (60.00)
Seizures	5 (4.17)
Others (fracture of facial bone and long bone injury, facial injury)	9 (7.50)
Age (y)	–	33.76 ± 17.3	28.5 (19–48)	4–72

Abbreviations: ENT, ear, nose, and throat; SD, standard deviation.

The most common mode of injury was RTA (85%), followed by assault (6.67%), fall from height (FFH; 6.67%), and fall from stairs and fall from train in 0.83% patient each ([Fig. 1]).

Fig. 1 Mode of injury distribution.

Incidence of Papilledema

Papilledema was present in 25 (20.83%) patients. Early papilledema was present in 1 (4.00%) patient and delayed papilledema in 24 (96.00%) patients. The mean ICP in patients without papilledema was 14.78 ± 4.12, whereas it was significantly higher in patients with papilledema, with a mean of 27.53 ± 4.36. The p-value for this comparison was less than 0.0001, indicating a statistically significant difference in ICP between the two groups.

CT finding demonstrated contusions in 74 (61.67%) patients, SAH in 37 (30.83%) patients, pneumocephalus with undisplaced bone fractures in 6 (5.00%) patients, and DAI in 3 (2.50%) patients. The GCS score at admission was 9 in 45 (37.50%) patients, 10 in 31 (25.83%) patients, 11 in 30 (25.00%) patients, and 12 in 14 (11.67%) patients. Management was conservative in 94 (78.33%) patients and surgical in 26 (21.67%) patients.

Association of Papilledema with Patient Condition

Compared with those without papilledema, patients with papilledema had significantly more contusions (84 vs. 55.79%, p = 0.011) and SAH (12 vs. 35.79%, p = 0.028), as shown in [Table 2].

Table 2 Association of CT finding with papilledema

CT finding	Papilledema absent (n = 95)	Papilledema present (n = 25)	Total	p-Value
Contusions	53 (55.79%)	21 (84%)	74 (61.67%)	0.011[a]
Pneumocephalus	6 (6.32%)	0 (0.00%)	6 (5%)	0.342[a]
SAH	34 (35.79%)	3 (12%)	37 (30.83%)	0.028[a]
DAI	2 (2.11%)	1 (4%)	3 (2.50%)	0.507[a]
Total	95 (199%)	25 (100%)	120 (100%)	–

Abbreviations: CT, computed tomography; DAI, diffuse axonal injury; SAH, subarachnoid hemorrhage.

^a Fisher's exact test.

There was a significant association of GCS at 24 hours with papilledema (p < 0.05) ([Table 3]). The outcomes were significantly better in patients who had no papilledema. Compared with patients without papilledema, patients with papilledema had significantly lower GOS scores (p < 0.05; [Table 4]).

Table 3 Association of Glasgow Coma Scale (GCS) at 24 hours with papilledema

GCS at 24 h	Papilledema absent (n = 95)	Papilledema present (n = 25)	Total	p-value
9	34 (35.78%)	11 (44%)	45 (37.50%)	0.0001[a]
10	26 (27.36%)	5 (20%)	31 (25.83%)	< 0.0001[a]
11	21 (22.1%)	9 (36%)	30 (25%)	0.019[a]
12	14 (14.73%)	0 (0%)	14 (11.67%)	< 0.0001[b]
Total	95 (100%)	25 (100%)	120 (100%)	–

^a Chi-squared test.

^b Fisher's exact test.

Table 4 Association of Glasgow Outcome Scale (GOS) with papilledema

GOS	Papilledema absent (n = 95)	Papilledema present (n = 25)	Total	p-Value
2	0 (0%)	8 (32%)	8 (6.67%)	< 0.0001[a]
3	5 (5.26%)	6 (24%)	11 (9.17%)	0.004[b]
4	41 (43.16%)	9 (36%)	50 (41.67%)	0.53[b]
5	49 (51.58%)	2 (8%)	51 (42.5%)	< 0.0001[a]
Total	95 (100%)	25 (100%)	120 (100%)	–

^a Fisher's exact test.

^b Chi-squared test.

Predictive Ability of Papilledema for Outcomes

The absence of papilledema demonstrated sensitivity of 96.87% (95% CI: 89.16–99.62%) specificity of 41.07% (95% CI: 28.10–55.02%), positive predictive value of 65.26% (95% CI: 54.80–74.74%), and negative predictive value of 92% (95% CI: 73.97–99.02%) with an AUC of 0.69 (95% CI: 0.60–0.77). The overall predictive accuracy of the absence of papilledema for good outcomes was 70.83%.

Discussion

Parsons first used the term papilledema in 1908 when it was discovered that elevation in the ICP may result in edema of the optical disc.[10] The association of papilledema with acute head trauma dates back to 1985 when Selhorst et al[11] first published the study, wherein 3.5% of the cases of acute head injury presented with papilledema. Since then, studies continue to explore the association of its occurrence with prognostication.

The mechanism of the development of papilledema in TBI is ascribed to the rise in subarachnoid pressure around the optic nerves, a phenomenon that is seen secondary to an elevation in the ICP in patients exposed to significant head trauma.[1] [2]

In our study, papilledema was seen in 25 (20.83%) cases. In comparison, in the study by Mattar et al,[3] papilledema was seen in 51.3% cases. In Kulkarni et al,[12] papilledema was present in 5.5% cases out of 200 patients with closed head injury. The difference may be due to the difference in the grade of injury among the patients.

Papilledema in itself is a grave symptom that may lead to loss of vision if it becomes prolonged and severe. Also, it may lead to injury of the nerve fibers and the nerve bundles if papilledema continues to late stages. Therefore, assessing early and late stages of papilledema is very important. We found that early papilledema was seen in 1 (0.83%) patient and late papilledema in 24 (20%) patients, whereas in Mattar et al[3] observed early papilledema in 31.9% cases and late papilledema in 19.4% cases.

Late papilledema usually occurs within 48 to 72 hours and early papilledema occurs within the first 24 hours of injury.[3] Our study holds importance since it was conducted on 120 cases of moderate head injury as against a previous similar study done on 72 patients with moderate head injury. The difference in the incidence and prevalence of early and late papilledema could be due to the heterogeneous population.

In our study, the causes of moderate head injury were assessed, which included RTA (85%), assault (6.67%), and FFH (6.67%). In other studies, Lafta and Sbahi[13] reported that the causes of TBI were RTAs and FFH in 37.1 and 23.9% of the patients, respectively. In an Indian study also, RTA was the most common mechanism (63%), and others were assaults (20%) as well as FFH (10%).[14] Kafle et al[15] also observed RTA to be most common cause (76%), followed by physical assault (4%).

Imaging holds a critical role in the evaluation of TBI not only from the diagnosis point of view but also for prognosticating the patients—similar to papilledema as done in our study. The standard protocol involves CT scan of the patients, which may be accompanied by MRI or functional MRI or diffuse tensor imaging. CT angiography has also been employed for cerebrovascular injuries. But first of all, CT scan remains a quick and affordable option for triaging, decision-making, and follow-up of the patients. It may help decipher epidural hematomas, fractures, leaks in the cerebrospinal fluid, or vascular injuries, in contrast to MRI, which is a relatively expensive option and may not be available in all the pathological settings. But axonal injuries are better detected by MRI.[16]

When we assessed the CT scan findings in relation to papilledema, we found that contusions were present in 74 (61.67%) patients, SAH in 37 (30.83%) patients, pneumocephalus in 6 (5.00%) patients, and no specific findings were detected in 3 (2.50%) patients. In line with our study, the study by Mattar et al[3] also found that papilledema was commonly seen in those cases who presented with hematomas, that is, SDH, EDH, or SAH. Moreover, these findings specifically show that raised ICP is seen in hemorrhage wherein fluid collection increases are specifically linked with papilledema and there is a significant correlation between imaging findings and papilledema.

In association with GOS prognostication, we found that patients who had papilledema had poor GOS scores as compared with those who did not have papilledema. Among other studies, Mattar et al[3] also observed similar findings as patients who developed early papilledema had worst GOS as compared with those without papilledema. Selhorst et al[11] assessed whether the presence of papilledema is associated with the worse prognosis as per the GCS. Patients with posttraumatic papilledema who had a higher GCS and milder, manageable increases in ICP were found to have lower severity of head injury. A significantly better outcome has been observed when compared with the mortality of severe injury patients (p < 0.05). Additionally, six patients who experienced persistently high ICP (>60 mm Hg) for ≥3 days did not develop papilledema, although all eventually died. The failure of papilledema to develop appears to be linked to the cessation of axoplasm production and transport in retinal nerve fibers, which seems to be due to the severity of the trauma.

In a study involving 200 patients with isolated closed head injuries, it was demonstrated that early eye examinations, when paired with the GCS, can help predict patient outcomes. The findings showed that signs like ocular motor paresis, papilledema, and pupillary involvement were associated with more severe head injuries, with a significant link between these ocular signs and the patient's prognosis (p = 0.003). The study also highlighted that out of 21 severe head injury cases, 8 (38%) patients with papilledema did not survive. The researchers inferred that early detection of these signs could potentially lower the rates of subsequent complications and death.

The findings of our study and other studies suggest that papilledema might be valuable for predicting outcome early in adults with moderate head injuries, in addition to its role in detecting and managing elevated ICP.[3]

Limitations

The duration of hospital stay of patients was not reported. Long-term outcomes such as 28-day mortality were not assessed. Restriction to moderate head injury and severe head injury cases were not taken. Other newer markers were not assessed such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and αII-spectrin breakdown product (SBDP145).

Conclusion

We report papilledema in 25 (20.83%) cases, with early papilledema in 1 (0.83%) patient and late papilledema in 24 (20%) cases. It showed a significant association with prognostication of patients in terms of GOS scores. The absence of papilledema carried 70.83% predictability for good outcomes. This shows that papilledema can be practically used as a simple bedside, novel marker for altered pulse rate, pupil size/reactivity, and raised ICP in patients with moderate head injury, in low-resource settings or emergency settings where ICP monitoring may not be feasible rapidly, and this may allow for better management of patients.

Conflict of Interest

None declared.

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Publication History

Article published online:
21 April 2025