The cloudy, dark, and sunny aspects of a dangerous and uncertain entity: Moderate traumatic brain injury

INTRODUCTION

Moderate traumatic brain injury (TBI) constitutes a prevalent entity often grouped with severe TBI. However, moderate TBI falls in a “gray zone of neurotrauma,” due to its variable and dynamic nature and the multiple controversies surrounding its management.^[1,2] Moderate and severe TBI share certain characteristics, such as the pathophysiology or the injury spectrum; however, their evolution during the acute phase differs and therefore demands different approaches.^[1,2] The epidemiology of moderate TBI varies according to the region’s resources and the analyzed population group.^[3-8] It is often associated with extracranial injuries, and patients are highly exposed to the risk of neuroworsening (NW).^[2,7-12] Its prognosis and outcomes continue to be disappointing.^[8-11]

Moderate TBI has cloudy, dark, and sunny aspects that must be recognized.^[1,2,13]

METHODS

In this narrative review, we discuss the main topics to consider in the modern management of moderate TBI, highlighting knowledge gaps and pointing out ways in which those gaps could be filled. To this purpose, we searched and reviewed published journal articles from PubMed using the following MeSH terms «Acute Brain Injury» [MeSH] OR «Traumatic Brain Injury» [MeSH] OR «moderate traumatic brain injury» [MeSH] OR «Intracranial Pressure» [MeSH] OR «Intracranial Hypertension» [MeSH] OR «Neuroimaging» [MeSH] OR «Neuromonitoring» OR «Neuroworsening» [MeSH].

Inclusion criteria were (1) population: adults (>18 years) admitted with moderate TBI and (2) post-resuscitation Glasgow Coma Scale (GCS) between 9 and 13 points.

Exclusion criteria were (1) pediatric patients, (2) mild or severe TBI, (3) neurologic worsening to GCS <9 before emergency room admission, (4) animal/in vitro studies; (5) experimental studies, and (6) studies with incomplete data.

The search was not limited per year but was limited to English or Spanish language. Clinical articles, reviews, and opinion papers were selected by all authors. In addition, the reference lists of all the retrieved articles were carefully examined to identify any further relevant manuscripts.

THE CLOUDY ASPECTS OF MODERATE TBI

a. Definition and categorization: There is no universal, widely validated definition of moderate TBI.^[14-16] TBI severity (mild, moderate, and severe) has been based primarily on the level of consciousness, as assessed by the GCS.^[17-20] In addition, both duration of consciousness impairment and the presence of post-traumatic amnesia have been used,^[21-25] [Table 1]. Conventionally, moderate TBI encompasses GCS scores between 9 and 12 points.^[21,26,27]

Several aspects require in-depth analysis.

• We consider that the term “moderate” is inadequate and does not reflect the dynamism and wide injury heterogeneity affecting this group of individuals.^[2,14-16] This is not just an issue of semantics: 9 points are not the same as 12 on the GCS.

• Several factors can impede or confound the correct determination of the GCS score, and these factors must be considered to avoid errors in categorization,^{[17-19,28-32]} [Table 2].

• GCS 13 should be considered within the moderate TBI category.^[16] GCS 13 is associated with a greater probability of having significant lesions on computed tomography (CT), developing NW, and requiring any surgical procedure.^[33]

  Predictive models from large clinical series support the inclusion of GCS 13 into the moderate TBI group.^[34,35] Indeed, the Brain Trauma Foundation (BTF) guidelines for TBI for management of combat victims also recommended this inclusion.^[36]

• Categorization: The labels of “mild,” “moderate,” and “severe” to classify TBI are outdated and imprecise. Recent evidence incorporates neuroimaging findings when categorizing TBI.^[8-11,37-41] The Marshall’s CT scale is the most validated and it is used worldwide.^[42] Alternative scales such as the Rotterdam scale or the modified British scale require additional validation.^[43,44] Serum biomarkers may add valuable information.^[45,46] Indeed, the American National Institute of Health proposed a re-categorization of the severity of TBI by incorporating clinical, imaging, biomarker, and modifying factors, including trauma kinetics, comorbidities, and social and demographic factors.^[47]

• Recently, a simple system to sub-categorize moderate TBI was proposed.^[28] The system is easy to apply at the bedside and adds CT findings (Marshall’s classification) to the GCS score in the so-called “traffic light method”^[28] [Figure 1]. Using this system, moderate TBI can be sub-grouped to predict the risk of NW.^[16,28] Following this approach, three subgroups were proposed: Low risk (green), high risk (yellow), and potentially severe TBI (red).^[16,28] Of note, the practical value of this proposal still requires external validation.

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Figure 1: Traffic light method for moderate traumatic brain injury categorization. GCS: Glasgow Coma Scale, MLS: Midline shift, NEML: Non evacuated mass lesions, PBC: Present basal cisterns, ABC:Absent basal cisterns, BCI: Basal cisterns impairment.

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b. Prevalence: Moderate TBI is common, even more than severe TBI. Prevalence ranges from 10% to 20%.^[1,2,13] Its frequency has been underestimated, often because moderate cases have been grouped together with severe TBI in many clinical studies. Despite the lack of studies addressing this situation,^[48] daily clinical practice allows us to observe that many individuals categorized as severe TBI were initially moderate (approximately 30%).

c. Changing epidemiological profile: In low-income countries where the chain of care from pre-hospital to rehabilitation is incomplete or suboptimal because of different socioeconomic factors, moderate TBI predominates in the young population (under the influence of alcohol or drugs), often resulting from road traffic accidents or violence.^[2-6,49,50] In contrast, in high-income areas, TBI predominates in older populations, being associated with multiple associated comorbidities (chronic obstructive pulmonary disease, heart disease, cancer), the use of antithrombotic or anticoagulants, and frequently resulting from falls or low-energy trauma.^[2-6,49,50]

Consequently, an increase in the prevalence of moderate TBI can be expected in the future, following the growth of this fragile and exposed population.^[51,52]

THE DARK ASPECTS OF MODERATE TBI

a. Absence of guidelines-Scarce literature: The ratio of severe/moderate TBI publications is around 4000– 5000/1. As previously mentioned, many studies mixed both populations under the umbrella “moderate-to-severe TBI.” Furthermore, while there are multiple guidelines that provide recommendations for mild and severe TBI,^[53,54] there are currently no guidelines for the management of moderate TBI. The Latin American Brain Injury Consortium Consensus for the Definition and Categorization of Moderate TBI constituted a valuable effort from a multidisciplinary group to highlight areas of needed research and provide practical guidance for the approach to patients with moderate TBI.^[16]

b. High risk of neuroworsening: NW is a serious complication after moderate TBI, and prevention and early detection are key in its management.^{[7-12,28,37,55]} Decades ago, a group of patients was described as those who “talked and died” (verbal GCS 3 or more points but then deteriorated and died).

Most of these patients belonged to the “moderate” group.^[56-62] NW is strongly associated with poor outcomes.^[8-12,55] The reported incidence of NW in moderate TBI varies from 15% to 40%, possibly due to the lack of a uniform and validated definition.^[7-11,37,55] A recent scoping review established a mean prevalence of 23.4%.^[12] In general, the definition of NW has been extrapolated from severe TBI and has been based on the clinical picture (deterioration of GCS, pupillary alterations, focal neurological deficit, and seizures);^[63-65] however, NW can be identified before any overt clinical deterioration by modifications on follow-up neuroimaging or neuromonitoring.^[48,66] Criteria to define NW specifically in moderate TBI have been recently proposed^[16] [Figure 2].

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Figure 2: Proposed algorithm to approach neuroworsening in moderate traumatic brain injury. CT: Computed tomography, GCS: Glasgow coma scale, NPi: Neurologic pupillar index, ICP: Intracranial pressure, SBP: Systolic blood pressure, ABC: Airway, breathing, circulation, ATLS: Advanced trauma life support, IV: Intravenous, ICU: Intensive care unit, TBI: Traumatic brain injury, PI: Pulsatility index

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The causes of NW are:^[48,66]

• Primary injury progression

• Secondary Insult (intra or extracranial)

• Iatrogenic.

NW can occur “early or late,” depending on whether it appears during or after the first 72 h post-injury,^[11,64,65] Some of the predictive factors of NW reported in moderate TBI are lower GCS, Marshall’s classification type III and IV, subdural hematoma, temporal or frontal-basal contusions, presence of extracranial lesions, higher injury severity score, arterial hypertension, and certain laboratory parameters such as high D-dimer and low platelet count.^[11,55,67]

c. Outcomes are poor in moderate TBI: Reported mortality in moderate TBI is close to 15%.^{[11,21,27,37,38,68,69]} Almost half of the individuals who have suffered moderate TBI will have long-term neurocognitive and psychological sequelae^{.[1,11,21,27,37,38,68,69]} The neurocognitive and neuropsychiatric sequelae share common characteristics with post-traumatic stress disorder.^[1] A recent TRACK-TBI study analyzing longitudinal profiles after moderate TBI using the disability rating scale (DRS) showed that at 2 weeks after moderate TBI, 84/106 (79.2%) had moderate disability or worse (DRS scores ≥4). However, by 1 year, 23/72 (32%) reported no disability (DRS score 0) and another 11/72 (15%) reported only mild disability on the DRS.^[70]

A study using the CENTER-TBI dataset (n = 1728) analyzed the systemic metabolic stress profile of TBI.^[71] Six endotypes were identified and 2 corresponded to the moderate TBI group (n = 310).^[69] Moderate TBI patients with normal metabolic profile had unfavorable outcomes in 56% of the cases, with a mortality rate of 29%.^[69] Meanwhile, moderate TBI patients with abnormal metabolic profiles had poor functional outcomes in 63% of the cases and mortality rates of 40%.^[69]

THE SUNNY ASPECTS OF MODERATE TBI

Patients with moderate TBI offer a unique opportunity for intervention. The importance of GCS after cardiopulmonary stabilization in the prognosis of individuals with severe TBI is widely known.^[53] The same occurs for the assessment of the primary injury on neuroimaging.^[42]

Although it is not specific to moderate TBI, one positive point to highlight is the possibility of early screening for intracranial hypertension and, subsequently, the risk of NW with non-invasive neuromonitoring techniques.^[71]

Determination of the optic nerve sheath diameter (ONSD) measurement is easy to perform, widely available, and has a short learning curve.^[71,72] It is a good tool for screening for intracranial hypertension, with excellent negative predictive value when the value is <5 mm.^[71,72]

Transcranial Doppler (TCD) is an extremely useful tool for the initial evaluation.^[73] Bouzat et al. studied the role of TCD in the prediction of NW and outcome of mild to moderate TBI.^[74] Pulsatility index >1.25 and diastolic velocity <25 cm/s showed good sensitivity (80%) and specificity (79%) to predict NW.^[74]

Pupillometry is not a good surrogate marker of intracranial hypertension.^[75] However, the neurological pupil index <3 showed a good prediction capacity for NW in the first 24 h post admission (p < 0001), with a sensitivity of 51.43% and specificity of 91.67%.^[76]

A recently developed non-invasive system analyzing pulsatile cranial expansion waveforms using a surface sensor allows the analysis of the ICP waveform, the analysis of the relationship between the P1/P2 components, and the time to reach the maximum peak (amplitude), which has shown a very good correlation with the invasive ICP.^[77,78] The analysis of the waveform allows the evaluation of the cerebral compliance, making it an integrative tool for the evaluation of the Intracranial Compartmental Syndrome.^[79]

Near-infrared spectroscopy uses two sensors positioned over the frontal lobes with light sources, providing regional oxygen saturation (rSO₂) and reflecting the balance between delivery and oxygen consumption and delivery.^[80] Despite its limitations, rSO₂ is a global indicator of cerebral oxygenation.^[80]

Electroencephalography in its different forms (intermittent, continuous, processed, and quantitative) can potentially detect seizures, non-convulsive status, and cerebral ischemia.^[80] In addition, it can assess sedation depth as well as identify patterns associated with poor outcomes.^[80]

Although non-invasive techniques present different limitations, they could be used as ancillary tools in different situations:

• Initial evaluation in emergency rooms

• Screening for intracranial hypertension

• Categorization

• Need for additional neuroimaging

• Supporting decisions to take in controversial scenarios

• Indication of invasive monitoring

• Surgical indication.

MANAGEMENT STRATEGIES

Proposed pathways for NW and general management of moderate TBI are depicted in Figures 2 and 3.

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Figure 3: Proposed pathway to moderate traumatic brain injury management. (a) Initial evaluation and categorization; (b) Management. SBP systolic Blood Pressure, ABC: Airway, Breathing, Circulation, CT: Computed tomography, ATLS: Advanced trauma life support, IV: Intravenous, ICU: Intensive care unit, TBI: Traumatic brain injury, ICP: Intracranial pressure, NPi: Neurologic pupillar index.

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All patients with moderate TBI should be hospitalized.^[16] In this context, the minimum conditions necessary for their adequate management are:^[16]

• Trained personnel in emergency and trauma management

• Availability of CT 24 h/7 days

• Availability of neurosurgery 24 h/7 days

• Availability of monitoring of basic physiological parameters

• Intensive care unit.

CLINICAL AND IMAGING MONITORING

The vital signs and the neurological status (GCS, pupillary semiology) should be strictly monitored,^[53] for example, every 30 min in the first 6 h post admission, and then every hour through the initial 24 h. After this period, clinical monitoring can be performed every 2–4 h if the patient remains stable or even more frequently in high-risk patients.

There are no clear recommendations about when to perform follow-up CT scans. It is reasonable to perform a cerebral CT scan at admission and then at 6 or 12 h, depending if the patient was admitted before or after 6 h after TBI.^[16] Subsequently, another CT scan is suggested 24 h after injury or earlier if there are clinical signs of NW.^[16]

CONCLUSION

Moderate TBI is a prevalent entity, encompassing patients with a wide injury spectrum, and it is frequently associated with extracranial injuries. Given the variability in injury severity, standardized risk stratification tools are essential to optimize clinical decision-making and allocate resources efficiently. Future studies should focus on validating risk assessment models, incorporating multimodal neuromonitoring, and developing consensus-driven guidelines to bridge the current gaps in care.