- Department of Neurosurgery, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
Correspondence Address:
G. Lakshmi Prasad, Department of Neurosurgery, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
DOI:10.25259/SNI_948_2024
Copyright: © 2025 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.How to cite this article: G. Lakshmi Prasad, Ashwin Pai, Swamy PT. Short course of low-dose steroids for management of delayed pericontusional edema after mild traumatic brain injury – A retrospective study. 24-Jan-2025;16:23
How to cite this URL: G. Lakshmi Prasad, Ashwin Pai, Swamy PT. Short course of low-dose steroids for management of delayed pericontusional edema after mild traumatic brain injury – A retrospective study. 24-Jan-2025;16:23. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=13344
Abstract
Background: Secondary insults such as brain edema is commonly observed after traumatic brain injury (TBI) and remains an important cause of neurological deterioration. Based on the corticosteroid randomisation after significant head injury (CRASH) trial findings, Brain Trauma Foundation guidelines recommend against giving steroids in TBI. However, the findings of two recent clinical studies suggest that there may be a subset of patients who may benefit from steroids.
Methods: This study was a retrospective, single-center, 4-year study. The study analyzed patients who had received systemic corticosteroids for pericontusional delayed edema after TBI. The time interval to steroid prescription, drug dosage, time to symptomatic improvement, and complications were analyzed.
Results: There were 19 males and eight females. Mean age was 42.1 years (range, 21–91 years). Except for one, all were mild TBI categories. All patients had brain contusions on computed tomography. Dexamethasone was used in tapering doses over 5–10 days, starting with 12 mg/day. The mean interval to steroid prescription after the trauma was 5.9 days, and the mean and median duration was 7 days. All, except one, had symptomatic improvement. The mean time to complete improvement in symptoms was 2.8 days. There were no complications pertinent to steroid usage in any of our cases.
Conclusion: This is the third clinical study to document the efficacy of systemic corticosteroids for delayed cerebral edema after TBI. As steroids are excellent drugs for vasogenic edema, the timing and dosage of steroids are two important factors that will determine their efficacy in TBI. We strongly feel that there needs to be more robust clinical trials with good patient numbers to confirm these findings.
Keywords: Cerebral edema, Corticosteroids, Dexamethasone, Steroids, Traumatic brain injury
INTRODUCTION
Secondary insult such as brain edema is commonly observed after traumatic brain injury (TBI) and remains an important cause of neurological deterioration.[
MATERIALS AND METHODS
This was a retrospective study over 4 years and was a single-center study. Patients in whom there was worsening/ non-improvement of symptoms and radiological evidence of persisting/worsening edema despite administration of standard cerebral decongestants such as mannitol/ hypertonic saline were prescribed steroids. As a protocol, no patients received steroids before a trial of decongestants. All patients received dexamethasone as the systemic steroid. It was administered parenterally for 24–48 h and was later converted to oral formulation, in tapering doses, for a total duration of 5–10 days.
Patient data were retrieved from hospital records. The following variables were analyzed: age, gender, mechanism of injury, Glasgow coma scale (GCS) score on admission, pupillary reactivity, radiological findings (contusion, subdural hematoma, basal cisterns, midline shift [MLS], etc.), time interval from initial trauma to deterioration (drop in GCS score or new/worsening of symptoms), symptoms (headache, giddiness, focal neurological deficits, and neurological deterioration), steroid dose prescribed, duration of steroids, time interval to clinical improvement, Glasgow outcome scale score at discharge and follow-up, and duration of follow-up.
RESULTS
We analyzed 27 cases in this study period. There were 19 males and eight females. The mean age of our study cohort was 42.1 years (range 21–91 years), and the median age was 41 years. Except for three, the mode of TBI was road traffic accidents (RTA) in all the other patients. There were 26 mild and one moderate head injury, and the latter was predominantly due to low verbal output due to left temporal contusion. The mean and median admission GCS scores were 13.9 and 15, respectively. There were no pupillary abnormalities or focal neurological deficits in any of the patients on admission. Two patients had hypertension.
Except for the patient with a moderate head injury, who had a drop in GCS score by 2 points, all others developed new-onset disabling headache or worsening of headache. Four patients had disabling vertigo as an additional new symptom. As noted earlier, steroids were prescribed only after a trial of cerebral decongestants (mannitol/hypertonic saline) and normalization of hyponatremia, if present.
On admission computed tomography (CT) scan, all patients were noted to have brain parenchymal contusions (14 unifrontal, seven bifrontal, and six temporal). Three patients had additional thin acute subdural hematoma (SDH), two patients had temporoparietal extradural hematoma (EDH) (operated), and one patient each had additional posterior fossa EDH, frontal EDH and cerebellar contusion. There was partial effacement of basal cisterns in five cases. Five patients had MLS, and the mean MLS was 1 mm (range, 0-6mm). In all cases, there was worsening of brain edema on CT imaging performed at the time of clinical worsening, with blooming of contusion noted in seven cases.
The mean time to steroid administration after the trauma was 5.9 days (range, 4–10 days), and the median time interval was 5 days. The mean duration of steroid prescription was 7 days (range, 5–10 days), and the median duration was 7 days. Symptomatic improvement was noted in all patients except one. The mean and median time to symptom resolution was 2.8 days and 3 days, respectively. In 14 cases, we performed a repeat CT after steroids. On follow-up scans, we noted that the cerebral edema persisted as earlier in five cases, while there was a reduction noted in nine cases. The mean and median GCS score at discharge was 15. There were no complications attributable to the steroids in any of our patients. The mean follow-up duration was 5.1 months (range, 2–10 months).
Since there was only one case that failed treatment with steroids, we did not perform statistical analysis as there won’t be any meaningful results from the analysis.
Representative case description
A 49-year-old male presented to our emergency services after an alleged RTA on the day of admission. He had occasional dull, aching, non-disabling headaches. On examination, he was conscious and alert with bilaterally reactive pupils. CT brain showed bilateral basifrontal contusions with focal mass effect [
DISCUSSION
The initial primary injury after trauma is followed by a secondary phase, which includes neuroinflammation, oxidative stress, and excitotoxicity.[
Glucocorticoids are among the most potent anti-inflammatory agents known to date. Inhibition of gene expression of pro-inflammatory molecules appears to be the primary mechanism of action of steroids.[
Before 2000, a number of randomized trials (with fewer participants) were published with regard to steroids and head injury. The majority of them were conducted in severe head injuries, and patients received high-dose steroids in the acute period.[
Recently, two clinical studies (one retrospective and one prospective) were published regarding the efficacy of dexamethasone in TBI-related contusions with surrounding edema. In the first study, steroids were prescribed to patients (the majority were mild TBI, severe TBI excluded) with contusions and pericontusional edema after a few days of the initial trauma, which was termed delayed cerebral edema. Steroids were given for a mean duration of 6.3 days, and the mean time interval from trauma to prescription was 7 days. It was concluded that low-dose steroids might benefit a subset of patients with pericontusional edema and persisting symptoms. [
With the results of these two clinical studies, one may take note of the fact that the CRASH trial results may not be uniformly applicable to all TBI patients. A subset of patients with contusions and vasogenic edema may benefit from corticosteroids. The following may be the reasons for contradictory observations between the medical research council (MRC)-CRASH trial and the recent two clinical studies: (a) First, the timing of administration of steroids. In the CRASH trial, steroids were given within 8 h of trauma, during which the edema is actually cytotoxic, and steroids have practically no benefit in such cytotoxic edema. (b) Second, the dosage of steroids used. In the CRASH trial, the steroid dose (high-dose methylprednisolone) was similar to the NASCIS trial. We feel that the spinal cord and TBI are different entities, and hence, similar dose steroids may not be beneficial or rather harmful in TBI. On the contrary, in the recent two studies, both the steroid formulation and doses were different to that in the CRASH trial (but similar between those two studies), wherein low-dose dexamethasone was prescribed in tapering doses for around 7–10 days. (c) Third, TBI is a very heterogeneous group and comprises diffuse axonal injury, contusions, subarachnoid hemorrhage, SDH, etc. The MRC-CRASH trial included all categories of TBI (GCS ≤ 14) and all radiological lesions such as acute SDH, diffuse edema, and contusions, while only mild TBI cases with contusions with pericontusional edema were included in the recent two studies.
In the present study, low-dose dexamethasone was prescribed in cases with contusions and pericontusional edema, and we did not include severe head injury cases. As noted in our previous pilot study, there may be a lag period between radiological improvement and clinical improvement.[
CONCLUSION
This is only the third clinical study to document the efficacy of systemic corticosteroids for delayed cerebral edema after TBI. As steroids are excellent drugs for vasogenic edema, the timing and dosage of steroids are two important factors that will determine their efficacy in TBI. Steroids may be of significant benefit to a subset of patients in whom the conventional decongestants have not benefited. We strongly feel that there needs to be more robust clinical trials with good patient numbers to confirm these findings.
Merits of the study
Only the third clinical study to document the efficacy of steroids in cases of TBI for delayed cerebral edema, post-CRASH trial results.
Drawbacks
The retrospective nature of the study, single-center study, and the smaller sample size were the main drawbacks of the study. The reasons for the small sample size have been mentioned earlier. Further, there was only one patient who failed steroid treatment, and hence, statistical analysis would not yield meaningful conclusions.
Ethical approval
The Institutional Review Board approval is not required as it is a retrospective study.
Declaration of patient consent
Patient’s consent not required as patients identity is not disclosed or compromised.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Disclaimer
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
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