“Talk and die” syndrome, a tragedy in traumatic brain injury: a cohort study

Abstract

Background

Traumatic brain injury is one of the leading causes of mortality worldwide. Some patients with traumatic brain injury die in the field shortly after gaining semi-consciousness. However, few reports have discussed the “talk and die” phenomenon and its underlying causes and risk factors.

Methods

We conducted a prospective study of 353 patients with head injury with a Glasgow Coma Scale score 9–14 who were admitted to the neurotrauma unit of a tertiary university hospital from January 2019 to June 2020 to investigate “talk and die” syndrome and its associated risk factors.

Results

Most study patients were male (66.3%). The major type of trauma was road traffic accident. Among the eight patients who experienced the “talk and die” phenomenon, five were male, while three were female; the age range was 16–71 years, and time to deterioration ranged from 4.5 to 30 hours.

Conclusion

The “talk and die” phenomenon can possibly be prevented. Although its prevalence is quite low, it is more likely to occur in older male patients with mild to moderate head injury. All patients with head injury should be well observed for not less than 30 hours; those with risk factors should be observed longer.

Trial registration Retrospective study protocol was approved by the institutional review board committee of Faculty of Medicine, Zagazig University, Egypt (#IRB10232).

Background

Traumatic brain injury (TBI) surpasses many medical disorders as one of the leading causes of mortality and morbidity worldwide, especially in developing countries [1, 2]. Some patients with head injury die shortly after a period of semi-consciousness after trauma, suggesting a devastating secondary brain injury. This phenomenon of death after a short lucid period was first described by Reilly et al. in 1975. The term “talk and die” refers to TBI patients with salvageable primary brain injury and short lucid period prior to clinical deterioration and subsequent death [3–5]. Generally, “talk and die” or “talk and deteriorate” indicates a lucid interval before brain herniation occurs and explains why patients with head injury are closely monitored for several days after the primary injury. The usual cause is delayed hemorrhage, such as epidural hematoma, which can be surgically managed if diagnosed properly [6].

Generally, the distribution of TBI outcomes exhibits a major health problem, with the majority of patients experiencing either death or short-term or long-term recovery. Most data suggest that a large proportion of TBI patients (even those with moderate injury) experience long-term problems. Nonetheless, some patients present with a lucid interval followed by deterioration and death, reflecting uncompensated brain damage. Understanding the primary causes of death and finding potentially preventable risk factors are the focus of continuous research [7].

In a recent meta-analysis and systemic review, the contributing factors and pathophysiology is not very clear. However, they conclude that the presence of intracranial hematomas in an initial brain scan, presenting with a low Glasgow Coma Scale (GCS) score, older age, and a lucid interval ≥ 24 hours are among contributing factors to a “talk and die” phenomenon following a traumatic brain injury [29].

This study aims to provide updated information regarding “talk and die” syndrome and presents our experience at a tertiary trauma center serving more than 7 million people [8].

Methods

We conducted a retrospectively review using a prospectively acquired database of 353 out of total of 497 patients (including those with severe TBI) with initial Glasgow Coma Scale (GCS) score 9–14 who were admitted to the neurotrauma unit of Zagazig University Hospital (Zagazig, Egypt) from January 2019 to June 2020. Inclusion criteria included talking upon admission (verbal component on GCS was ≥ 3). The endpoint was in-hospital mortality. We excluded patients with severe extracranial injuries with Injury Severity Score (ISS) threshold of 15 or more and those with GCS score 3–8 [25]. The following data were collected by the authors using charts and reports of patients: age; sex; mode, type, and time of trauma; GCS score on admission; blood pressure; medical comorbidities; and Marshall computed tomography (CT) classification score. The study has been approved by a local ethics committee. All patients included in the study reached the hospital within 2–3 hours of the time of injury and were evaluated according to our protocol for polytraumatized patients; this included a head CT and other routine radiological examinations. Head CT was also performed after admission and at the time of clinical deterioration. One more CT brain scan was performed 24 hours after surgical intervention if there was any. Quantitative data are expressed as means and medians. Qualitative data are expressed as numbers and percentages.

Results

Patient characteristics

Patient characteristics are summarized in Table 1. Of the patients, 234 were male (66.3%), and 64.6% were aged 15–45 years. Mean age overall was 33.7 (range, 5–73) years. The most common type of trauma was road traffic accident (RTA) (51.6%). Among the eight patients who died (2.3%), five were male, and the mean age was 47.5 years (range, 16–71). The mean age in the group of patients who survived was 31.2 years.

Table 1.

Patient characteristics in the prospective cohort

Variable	Total number	Alive	Dead
Number of patients (%)	353 (100%)	345 (97.7%)	8 (2.3%)
Mean age (years)	33.7	31.2	47.5
Male (%)	234 (66.3%)	225 (65.2%)	5 (62%)
Mode of trauma
Road traffic accidents	182	177 (51.3%)	5 (62.5%)
Fall from height	93	91 (26.4%)	2 (25%)
Assaults and fighting	67	66 (19.1%)	1 (12.5%)
Other	11	11 (3.2%)	0 (0%)
Median GCS score on admission	13	14	11
Predominant comorbidity
Coagulopathy	11	9 (2.6%)	2 (13.3%)
Hypertension	62	59 (17.1%)	2 (20%)
Diabetes	59	57 (16.5%)	1 (13.3%)
Ischemic heart	23	22 (6.4%)	0 (6.7%)
Stroke	7	7 (2.1%)	0 (0%)
Malignancy	2	2 (0.6%)	0 (0%)
Hepatic dysfunction	69	65 (18.8%)	2 (26.7%)
Renal dysfunction	19	17 (4.9%)	1 (13.3%)
Chest dysfunction	13	12 (3.5%)	0 (6.7%)
None	95	95 (27.5%)	0 (0%)
Initial Marshall CT score
I	23	23 (6.6%)	0 (0%)
II	125	123 (35.7%)	2 (12.5%)
III	84	81 (23.5%)	3 (37.5%)
IV	63	61 (17.7%)	2 (25%)
V	44	43 (12.5%)	1 (12.5%)
VI	14	14 (4.0%)	0 (0%)

GCS Glasgow Coma Scale, CT computed tomography

Clinical predictors

The most frequent GCS score overall on admission was 13 (33.5%), whereas the least frequent score was 14 (6.4%). The most frequent motor score was 5 (40%), whereas the least frequent score was 1 (5.8%).

Among the eight patients who died, the most frequent GCS score on admission was 11. After deterioration, a GCS score of 3 was observed in two patients (25%). The time interval for deterioration ranged from 4.5 to 30 hours. Two patients clinically deteriorated from GCS score 11 to 3.

Radiological predictors

The most frequent initial Marshall CT score [9] was II, which was found in 123 of 345 survivors (35.7%). For the “talk and die” group, it was II (12.5%) or III (37.5%). The least frequent score was VI in the survivors group and I and VI for those who died (Table 2). Some head CT scans performed at the time of clinical deterioration showed surgical hematomas. Patients with scans showing brain swelling and midline shift underwent decompressive craniectomy unless GCS score was 3. Delayed surgical hematomas were epidural in two of eight patients who died, as shown in Figs. 1 and 2. Acute subdural hematomas were found in four patients, as shown in Figs. 3 and 4. Other pathologies responsible for clinical deterioration were intracerebral hematoma, contusion, subarachnoid hemorrhage, and increased brain edema. For patients with increased brain edema, decompressive craniectomy is the only treatment option for patients not responding to optimal medical treatment, as our center does not have intracranial pressure (ICP) monitoring capability.

Table 2.

Initial Marshall CT score across different categories, indicating outcomes for patients who were alive or deceased

Figure 1.

A Axial bone window view of the computed tomography scan of the head upon admission showing a right parietal fracture (hollow arrow). B Axial view of the computed tomography scan of the head obtained after clinical deterioration showing a right parietal epidural hematoma. C An intraoperative image after craniotomy shows the clotted hematoma beneath the removed bone flap. D An intraoperative image after hematoma evacuation shows sunken dura mater and “tenting sutures” in place

Figure 2.

A and B Two axial views of the computed tomography scan of the head upon admission of a patient with head injury showing an epidural rim of anterior temporal blood and proptosis of the right eye. C and D Follow-up computed tomography scan of head shows a delayed acute right temporoparietal epidural hematoma. There is significant midline shift with effacement of the ipsilateral lateral ventricle and brain edema. E and F Two axial views of the postoperative computed tomography scan of head showing complete evacuation of the hematoma and brain edema

Figure 3.

A An intraoperative image shows the congested dura mater in a patient with an acute subdural hematoma. B After dural opening, clotted and semi-clotted subdural blood and edematous brain are visualized. C An intraoperative image shows brain with posttraumatic subarachnoid hemorrhage underneath a wide dural opening

Figure 4.

A An intraoperative image shows blue/gray dura mater, indicating an acute subdural hematoma beneath. B After wide dural incisions, subdural blood drained from underneath. C A duroplasty with a graft from the galea aponeurotica of the scalp was performed to allow additional space for the edematous brain

Characteristics of the patients who presented with mild and moderate head injuries and then experienced the “talk and die” phenomenon are shown in Table 3.

Table 3.

Glasgow Coma Scale score, demographics, cause of death, and surgical intervention in patients who experienced “talk and die” syndrome

Patient number	Age in years/sex	GCS at admission	Worst GCS	ISS	Time from injury to deterioration in hours	Main intracranial pathology	Operation
1	39/M	12	7	25	16	EDH + contusions	Craniotomy
2	62/F	13	5	33	4.5	ASDH + brain edema	Decompressive craniotomy
3	71/M	11	4	26	14	EDH	Craniectomy
4	16/F	9	5	29	18	EDH + brain edema	Craniotomy
5	44/M	10	6	35	30	ASDH + ICH + contusions	Craniotomy
6	54/F	11	3	26	16	DAI + brain edema	—
7	35/M	14	7	27	15.5	ASDH + ICH	Craniotomy + second craniotomy
8	59/M	11	3	25	21	Brain edema + contusions + SAH	—

GCS Glasgow Coma Scale, ASDH acute subdural hematoma, EDH epidural hematoma, ICH intracerebral hematoma, DAI diffuse axonal injury, SAH subarachnoid hemorrhage

Discussion

The “talk and die” phenomenon

The “talk and die” phenomenon refers to patients who can articulate speech after head injury prior to clinical deterioration and death. Several reports have studied this phenomenon after the initial description by Reilly et al. [5, 10, 11]. Generally, TBI is classically classified into two types of injury: primary, at the time of impact, and secondary, after the primary injury. Secondary injuries can be prevented if the patient is managed promptly after hospital transfer from the trauma scene. Timely management should keep the lucid interval concept in mind [7]. When a patient talks after injury, it is assumed that the primary injury has not been severe. However, any aggravation of primary or secondary brain injuries can cause clinical deterioration [12].

In the pathophysiology, compensatory mechanisms such as venous drainage and cerebrospinal fluid (CSF) displacement cause a lucid interval, which is a temporary stabilization. Herniation syndromes can cause brain stem compression, while increasing intracranial pressure (ICP) can cause cerebral ischemia and subsequent damage. Although early intervention increases survival, irreparable brain stem injury from delayed treatment frequently leads to catastrophic consequences [30].

“Talk and die” syndrome is a tragedy of medical rescue. This syndrome should be avoided by using multiple monitoring methods, not only invasive ones but also surgical tertiary methods including ICP monitoring or transorbital sonography, CSF intraventricular drainage, and decompression. Unfortunately, ICP blot is not available in our hospital, which is a limitation. Both invasive and non-invasive monitoring can predict the loss of balance with the Monro–Kellie doctrine, as well as buffer the unbalance of doctrine and failure of compensation and unavoidable brain herniation [26].

Treatment strategy

Treatment—either conservative management or surgical management—is crucial, and defining the key surgical point at the right time is even more important. Moreover, osmolarity monitoring, hyponatremia, hypokalemia, hypotension, or intracerebral hyperperfusion can deteriorate the edema as well as intracranial pressure and result in sudden death, or accelerate the herniation [26].

Although there have been significant improvements in the management of the cases of patients with TBI, early clinical worsening can still occur, as illustrated by the concept of “talk and die.” However, the pathophysiological basis of this phenomenon has not yet been elucidated. To implement effective preventive and treatment strategies for “talk and die” syndrome, accurate information regarding characteristics of this condition is essential [13].

Previously reported incidence rates of “talk and die” syndrome vary from 2% to 7%. [6, 11, 14, 15]. In our study the incidence was 2.2%, which is in the lower range, suggesting that the incidence of “talk and die” syndrome has been decreasing over the last few decades due to modern advances in neurotrauma care. However, more efforts are still needed to further reduce its incidence in the future.

Prognostic factors

TBI outcome is influenced by many factors, including type and severity of trauma. In high-impact trauma, the patient may die at the scene, usually due to severe primary brain injury and/or associated extracranial injuries. The most common primary traumatic cerebral injury is diffuse axonal injury (DAI), which is detected at autopsy in 100% of fatal severe TBI patients (GCS score ≤ 8) [16]. Extracranial injuries may aggravate the primary insult by several mechanisms, the most important of which is hypotension resulting from hypovolemic shock [17].

In mild to moderate brain injuries (GCS score 9–14), most patients exhibit a verbal response score ≥ 3. DAI is not uncommon, however, and clinical deterioration due to delayed hematoma or worsening brain edema is common. The most common mode of trauma in mild to moderate brain injuries is road traffic accidents, and male patients are mostly affected. In our study, the most frequent GSC score in those who experienced “talk and die” syndrome was 11, indicating moderate brain injury. The time interval for deterioration in our study ranged from 4.5 to 30 hours. In other studies, however, this interval could be up to 48 hours [18]. One study even reported a fully conscious patient who deteriorated to fixed and dilated pupils on the third day after trauma, which was attributed to delayed intracerebral contusions and excessive opioid use with secondary respiratory depression [6].

In agreement with other studies, we found that “talk and die” syndrome is more likely in older male patients with moderate head injury. Brain compliance decreases and prevalence of comorbidities increases with advanced age. In addition, the male population is known to be more prone to head injuries. In our study, patients with mild head injury less frequently experienced “talk and die” syndrome. This may be due to the more intensive monitoring and care offered to patients with moderate head injury as compared with those with mild head injuries. All the patients who died in our study had head injuries classified as moderate head injury, and their most frequent GCS score was 11. The time interval and mode of deterioration varied, however, as brain compliance differs between individuals, even for patients of the same age. Cerebral blood flow (CBF) is affected by cerebral arterial compliance, and the diameter of the cerebral vasculature and degree of macro- and microvascular vasospasm varies depending on the degree of brain insult and cerebral edema [6, 18, 19, 31].

The Marshall classification grades TBI on the basis of head CT findings to predict outcome. Though introduced in 1991, it remains the standard. Several modifications have since been developed, but the initial classification scheme has not been replaced [2, 9, 20]. In a study comparing the Marshall and Rotterdam scores for patients with moderate and severe head injury, both were reliable in predicting outcome and mortality. Both may be identical, but the Rotterdam system uses some additional information, such as subarachnoid hemorrhage (SAH). So, the Rotterdam system is more suitable for diffuse injuries. We opted to use the Marshall score in this study [21].

In a previous study, the most common Marshall score for both survivors and deceased patients was II [9]. In contrast, we found a Marshall score of III was most common in the “talk and die” subgroup (37.5%), while for survivors, the most frequent score was II, detected in 123 (35.7%) patients [21]. We believe that a classification system based on imaging is insufficient for predicting outcome. In cases of surgical hematoma, outcome is mostly reliant on other factors (for example, type of hematoma): mortality varies from 7% to 12.5% in epidural hematoma, 16% to 72% in brain contusions, and 40% to 60% in acute subdural hematoma [22].

The pathophysiology of the “talk and die” phenomenon is not well understood. However, according to the Monro–Kellie doctrine, a sudden increase in intracranial pressure occurs in response to increased intracranial blood, brain, or cerebrospinal fluid volumes at a limiting point where brain compliance fails to accommodate any extra volume. Once this point is reached, medical or surgical intervention is crucial to stop or reverse clinical deterioration. Although this appears to be the most acceptable explanation, there remains no consensus. Further experimental research is needed [23].

In a study, quantitative electroencephalogram (EEG) and EEG reactivity may be used for the early prognosis of patients with severe traumatic brain injury. Relative alpha variability and EEG reactivity were associated with poor prognosis [27].

The role of cardiorespiratory pattern during the progress of brain traumatic effect was investigated in 110 patients. Common electrocardiogram (ECG) changes were recorded and improved in those underwent surgical decompressive craniectomy. Generally, left ventricular dysfunction on admission was associated with low admission and discharge GCS and overall poor prognosis [28].

Limitations

Our study is limited by its single-center, population-based design; the small number of patients studied; predominantly young population, which is a major contention when drawing conclusions; and the lack of ICP monitoring capability at our institution. In addition, we did not evaluate hyponatremia or other biomarkers; however, none of the patients who died had electrolyte disturbances. The role of EEG, breathing patterns, and ECG changes were not included in data. Future multi-institution prospective studies are warranted. Moreover, most previous studies included patients with extracranial injuries, which was an exclusion criterion in our study [24]. Prompt management should be based on clinical deterioration and not ICP monitoring; delays in CT scanning or surgical intervention should be avoided, as they are preventable causes of death in the ‘‘talk and die’’ phenomenon [15].

The absence of intracranial pressure monitoring may delay the diagnosis, as this is a further poorer outcome. Finally, the use of all tools such as EEG and other biomarkers is the key for multidisciplinary team management rather than repeated CT head scans.

Conclusion

“Talk and die” syndrome is a well-established phenomenon that can possibly be prevented. Although its prevalence is quite low, it is more likely to occur in older male patients with mild head injury. Special attention among junior neurosurgeons should be paid to a lucid interval in patients with moderate head injury. All patients with head injury should be observed for not less than 30 hours; those with risk factors should be observed longer. Any clinical suspicion should be confirmed by timely investigation via head CT. We recommend accruing data about TBI from different large trauma centers across the globe and performing a meta-analysis.

Author contributions

Mohamed M Arnaout: conceptualization, data collection, methodology, data collection, writing—original draft preparation, supervision, writing—review and editing, and approval of the final manuscript. Mansour A Mekia: conceptualization, data collection, methodology, writing—review and editing, revision, and approval of the final manuscript. Ahmed A Bessar: conceptualization, data collection, methodology, writing—review and editing, and approval of the final manuscript. Magdy O ElSheikh: conceptualization, data collection, methodology, supervision, writing—review and editing, and approval of the final manuscript.

Funding

Not applicable.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

Ethical approval was waived by the local ethics committee in view of the retrospective nature of the study and the fact that all the procedures being performed were part of routine care. All methods were carried out in accordance with relevant guidelines and regulations. Study protocol was approved by institutional review board committee of the Faculty of Medicine, Zagazig University, Egypt. #IRB10232. Informed consent was obtained from included subjects and/or their legal guardian, as a routine oral/written consent is waived for every admission to emergency university hospital. In the presented data, confidentiality was maintained through anonymization of the data.

Consent for publication

Written informed consent was obtained from the patient or from the patient’s next-of-kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

Not applicable.