Post-Concussion Syndrome—Epidemiology and Diagnosis Criteria: History
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Head injuries, mild traumatic brain injuries (TBIs) in particular, are a significant concern due to their potential to create long-term health consequences, such as post-concussion syndrome (PCS) and chronic traumatic encephalopathy (CTE). PCS is a sequela of mild TBI, with a prevalence rate of 29–90% among patients who have suffered a head injury.

  • mild traumatic brain injuries
  • post-concussion syndrome
  • diagnosis

1. Introduction

Head injuries, mild traumatic brain injuries (TBIs) in particular, are a significant concern due to their potential to create long-term health consequences, such as post-concussion syndrome (PCS) and chronic traumatic encephalopathy (CTE) [1].
Despite the fact that the underlying mechanism of concussion is still not fully described, it has been shown that the stretching and disruption of neuronal and axonal cell membranes actively participate as triggers of neurometabolic cascade activation, leading to neuronal and axonal injury and death. On the other hand, these mechanical damages to brain tissues could determine neuroinflammation and microglia activation that could further contribute to the short and long-term complications [2][3].
Several classification systems for TBIs have been proposed to reflect the pathophysiological aspects. However, since most of these classification systems and diagnostic criteria are based on clinical observations and symptomology, there are only a few that are widely used in diagnosis [4]. In this way, TBIs can be classified based on severity, pathoanatomic type, outcome, and prognosis [5]. The Glasgow Coma Scale (GCS) is commonly used to classify TBIs as mild (GCS score of 13–15), moderate (GCS score of 9–12), or severe (GCS score of 3–8) [6]. The extent of post- or peri-traumatic amnesia is another important factor in determining TBI severity. A TBI with post-traumatic amnesia of 1–24 h is considered moderately severe, but more recent classifications of moderate TBI require post-traumatic amnesia lasting beyond 24 h [7][8].
One widely accepted TBI classification system is the Mayo System (Table 1), which categorizes TBI as possible, probable—mild, and definite moderate-severe [8]. However, the most problematic aspect of this classification system remains the mild TBI, as their criteria refer to blurred vision, confusion, headache, or nausea, any loss of consciousness for less than 30 min, post-traumatic amnesia for less than 24 h, and a depressed, basilar, or linear skull fracture with intact dura matter that can often be missed during the initial imaging scans. Moreover, GCS could be administered to the patients at 30 min following the head trauma due to their loss of consciousness. The Mayo Classification System also requires the exclusion of other causes of impaired consciousness. Furthermore, the additional evidence of brain hematoma, hemorrhage, contusions, or ruptured dura matter categorizes the observed TBI as moderate-severe [9], even though mild TBIs could also be characterized by significant changes of the brain molecular pathways.
Mild TBIs are a major public health issue, affecting more than 69 million patients a year worldwide. PCS, although widely recognizable, remains a controversial entity. Both mild TBI and PCS are currently clinically diagnosed based on symptomatology and, in some cases, brain imaging evaluation. The current state of research on saliva biomarkers and their clinical applications is promising, but most studies focused on miRNAs, and only a few studies investigated the role of EVs, NfL, and S100B. The critical outcome of salivary biomarkers’ current state is that miRNAs and other non-coding RNAs, combined with clinical history and examination, self-reported symptoms, and clinical–paraclinical cognitive and balance testing, can provide a non-invasive alternative diagnostic methodology to the currently approved plasma and cerebrospinal fluid biomarkers.
Table 1. Mayo system of TBIs classification [8][9].

2. Post-Concussion Syndrome—Epidemiology and Diagnosis Criteria

PCS is a sequela of mild TBI, with a prevalence rate of 29–90% among patients who have suffered a head injury [1]. There is no universally accepted definition for PCS, but it is typically characterized by at least three symptoms, such as headache, fatigue, irritability, dizziness, balance issues, disturbed sleep, poor memory and concentration, and increased sensitivity to light and noise. These symptoms appear shortly after a head injury and can persist for weeks or months. When the symptoms persist for more than six months or one year, the condition is referred to as prolonged PCS (PPCS) [10].
The more benign International Classification of Diseases, Tenth Revision (ICD-10) diagnostic criteria for PCS include a history of TBI and three or more symptoms, such as headache, dizziness, fatigue, irritability, insomnia, concentration or memory disturbance, and intolerance to stress, alcohol, and emotions, providing a psychogenic approach in diagnosis [1][11][12]. On the other hand, the American Psychiatric Association’s Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defines PCS as a major or mild neurocognitive disorder due to traumatic brain injury, which requires evidence of traumatic brain injury with any of the following symptoms: loss of consciousness, post-traumatic amnesia, disorientation and confusion, new onset of seizures, anosmia, or hemiparesis; this approach focuses more on the post-TBI cognitive decline evaluation, thus offering a neurogenic approach in diagnosis and recovery prognosis [12][13].
Recent studies described the consequences of post-concussive injury as being persistent for a longer period, leading to the notion that the long-term effects of PCS go beyond just neurological traits. In this context, Clark et al. recently suggested that the concept of PCS could not be unidimensional but framed in a bio-psycho-socio-ecological model, in a facile manner [14]. The neurocognitive symptoms, for example, occur directly after the TBI or immediately after regaining consciousness, and could persist for longer than the acute post-injury period [13]. Moreover, it was shown that the neurocognitive impairments seen in PCS result due to complex mechanisms involving neurodegeneration and neuroinflammation, the latter starting from the acute post-injury period.
Thus, not only the psychogenic and neurogenic approach in diagnosis could be considered, but also the molecular approach. While multiple molecular biomarkers have been recently described in mild TBIs and PCS, their specificity is still under debate. Moreover, as non-invasive evaluation is preferred in emergency medicine, recent research has shown that salivary biomarkers can be essential in diagnosing PCS. As saliva contains a wide range of biomolecules that are indicative of various physiological processes, such as hormones, proteins, and microRNAs, several salivary molecules, including S100B, neurofilament light chain (NfL), micro RNAs, and exosome vesicle proteins, have been found to be associated with mild TBIs and PCS; these are thus potent specific biomarkers, offering a promising tool for the early detection and management of PCS and CTE.

This entry is adapted from the peer-reviewed paper 10.3390/diagnostics13081367


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