The change of serum and CSF BDNF level as a prognosis predictor in traumatic brain injury cases: A systematic review
Authors: Turchan Agus , Fahmi Achmad , Kurniawan Achmad , Bajamal Abdul Hafid , Fauzi Asra , Apriawan Tedy 
Published: June 2022

Background:
Mortality predictions following traumatic brain injury (TBI) may be improved by including genetic risk in addition to traditional prognostic variables. One promising target is the gene coding for brain-derived neurotrophic factor (BDNF), a ubiquitous neurotrophin important for neuronal survival and neurogenesis.

Methods:
A total of seven publications pertaining to BDNF in the study of traumatic head injury were included and reviewed. The majority of patients were male, that is, 483 (83.85%) patients, compared to 93 (16.15%) female patients. The median length of follow-up was 6 months (3 days–12 months). Measurement of the patient’s initial condition was carried out by measuring the initial GCS of the patient at the time of admission across the five studies being 6.5. The median CSF BDNF levels in the unfavorable group being 0.2365 (0.19–0.3119) ng/ml, from favorable group which was 0.20585 (0.17–0.5526) ng/ml. The median serum BDNF level in the unfavorable group being 3.9058 (0.6142–13.0) ng/ml, from favorable group which was 4.3 (0.6174–23.3) ng/ml.

Results:
Six studies reported on the sex distribution of patients, the majority of patients were male, that is, 483 (83.85%) patients, compared to 93 (16.15%) female patients. Six studies reported the number of patients per outcome group. The comparison of the number of patients in the two groups was quite balanced with the number of patients in the good group as many as 269 patients (55.5%) and the number of patients in the unfavorable group as many as 216 patients (44.5%). Measurement of the patient’s initial condition was carried out by measuring the patient’s initial GCS at the time of admission. It was reported in five studies, with the overall mean baseline GCS across five studies being 6.5 (3.2–8.8). Measurement of patient outcome was carried out by several methods, two studies used Glasgow Outcome Scale, Glasgow Outcome Scale Extended was used in two studies, and five studies used survival as a patient outcome measure. The patient’s BDNF level was measured in CSF and/or serum. A total of four studies measuring BDNF CSF levels and serum BDNF levels. Measurement of BDNF levels in TBI patients conducted on patients in seven literatures showed that there were differences in the trend of BDNF levels from CSF sources and serum sources. Measurement of CSF BDNF levels CSF BDNF levels was reported in two of the seven literatures, with the median CSF BDNF level in the unfavorable group being 0.2365 (0.19–0.3119) ng/ml. CSF BDNF levels were higher than the median in the preferred group, which was 0.20585 (0.17–0.5526) ng/ml. The results of the analysis from three other literatures stated that there was a tendency for lower CSF BDNF levels in the preferred group. Serum BDNF levels were reported in two of the seven literatures, with the median serum BDNF level in the unfavorable group being 3.9058 (0.6142–13.0) ng/ml. This serum BDNF level was lower than the median in the preferred group, which was 4.3 (0.6174–23.3) ng/ml. The results of the analysis of four literatures reporting serum BDNF stated that there was a tendency for lower serum BDNF levels in the poor group. A risk assessment of bias for each study was performed using ROBINS-I because all included studies were non-RCT studies. Overall the results of the risk of bias analysis were good, with the greatest risk of confounding bias and outcome bias.

Conclusion:
Serum BDNF levels were found to be lower in the unfavorable group than in the favorable group. This is associated with an increase in autonomic function as well as a breakdown of the blood–brain barrier which causes a decrease in serum BDNF levels. Conversely, CSF BDNF levels were found to be higher in the unfavorable group than in the favorable group. This is associated with an increase in the breakdown of the blood–brain barrier which facilitates the transfer of serum BDNF to the brain, leading to an increase in CSF BDNF levels.