Reframing Postconcussional Syndrome as an Interface Disorder of Neurology, Psychiatry and Psychology

Camilla N. Clark; Mark J. Edwards; Bee Eng Ong; Luke Goodliffe; Hena Ahmad; Michael D. Dilley; Shai Betteridge; Colette Griffin; Peter O. Jenkins


Brain. 2022;145(6):1906-1915. 

In This Article

Approaching Mild Traumatic Brain Injury as an Interface Disorder

The syndrome of persistent symptoms following mTBI rests at the interface between neurology, neurosurgery, psychiatry and psychology. Far from being a 'one-size fits all' condition, mTBI is a complex condition with multiple potential underlying pathophysiological and psychopathological processes, requiring a range of interventions across numerous specialties. A novel approach focusing on pathology and impairment-based diagnostics would allow accurate and timely diagnosis of the often complex symptoms occurring after mTBI.[20]

Preinjury Factors

Pre-injury depressive or anxiety disorder are the strongest predictors of persistent symptoms after mTBI.[21,22] Additional factors that influence recovery include pre-injury life events, social circumstances, personality traits including neuroticism and memory perfectionism, illness expectation and beliefs.[23–25] Expectations relevant for outcome include beliefs about symptom duration, the strength of identity and the emotional impact of the TBI.[26–28] Pre-existing anxiety and anxiety sensitivity are associated with more severe and prolonged symptom reporting, potentially related to negative illness beliefs.[29,30]

Pre-injury neurodegeneration or even healthy ageing affect the outcome of the injury regardless of its severity.[31,32] In addition, it is likely that pre-existing neurodevelopmental disorders would have an impact on outcome after mTBI. Premorbid psychiatric illnesses including attention deficit hyperactivity disorder are seen in a higher proportion of those with mTBI than would otherwise be expected.[33–35] This may relate to impulse control behaviours, including alcohol and substance misuse, which can predispose an individual to sustaining a TBI. These examples indicate that the neural substrate on which the injury occurs interacts with the effect of the injury itself.

The Injury: To What Extent has Persistent Damage Occurred?

A TBI results from an external mechanical force which is hypothesized to cause a primary injury. However, the mTBI group comprises a huge range of injury severity. Within this same category might be a person who sustained a very minor blow to the head resulting in symptoms such as dizziness, headache and nausea and a person who, following a blow to the head, had 29 min of loss of consciousness, 23 h of post-traumatic amnesia and a non-displaced skull fracture. It seems logical that the physical consequences to the brain are likely to differ across this spectrum.

Despite this complexity, there often appears to be an assumption in the literature that symptoms after mTBI are always caused by the same basic process of brain injury at a cellular and structural level and, therefore, that experimental studies at a group level are a reasonable way to investigate the nature of these injuries.[36] This fails to recognize the heterogeneity of likely physical injury within the broad mTBI category and also, crucially, that other disorders can cause persistent symptoms after mTBI (e.g. functional neurological disorder, depression, migraine) which are themselves associated with abnormalities on experimental measures such as functional MRI.[37–39]

Post-mortem studies of patients with a history of mTBI, but who died of other reasons, have found evidence in some of white matter injury and persistent inflammation months after the injury.[40,41] Secondary injury could therefore develop in minutes, hours or months, with possible long-term effects on symptoms and function.[42] However, caution must be applied, because these phenomena are likely to affect only a proportion of people with mTBI. There is also a tendency to extrapolate in an unrestrained way the results of animal studies to humans, even though the vast range of injury severities in humans with mTBI do not map well onto the carefully controlled experimentally-induced injuries in animal studies.

Use of Brain Imaging to Define Extent of Brain Damage After Mild Traumatic Brain Injury

Advances in brain imaging techniques have allowed the possibility of examining the presence of post-TBI pathophysiological changes in vivo. However, several potential pitfalls exist in the interpretation of neuroimaging results in people with persistent symptoms after mTBI. These include (i) the sensitivity of routine clinical and advanced imaging techniques for detecting injury after mTBI; (ii) the specificity of any abnormalities detected; (iii) their role in prognostication; and (iv) their relationship to persistent post-trauma symptoms. Over (or under) interpretation of imaging findings can lead to misdiagnosis in an individual and consequently inappropriate treatment and prognostication. At a research level, insufficiently powered studies or incorrect extrapolation of imaging findings to underlying pathophysiology can also lead to inappropriate conclusions being formed.

A variety of imaging methods are sensitive to changes in brain structure (e.g. volumetric and diffusion tensor imaging), functioning (e.g. functional MRI and magnetoencephalography) and alterations in cellular and biochemical milieu, including evidence of persistent inflammation (e.g. PET).[43–45] Using these methods, numerous studies have identified imaging changes at a group level in those with persistent symptoms after mTBI.[1] However, these changes are inconsistent and cannot easily be extrapolated to single cases of mTBI.[46–48]

It is also important to recognize that potential imaging changes may not necessarily be a direct consequence of the mTBI itself. Co-morbid conditions which might be relevant for causing persistent symptoms after mTBI, but not via structural damage, can also cause detectable changes using these neuroimaging techniques. For example, diffusion tensor imaging metrics have been shown to be altered in migraine,[49,50] depression[51] and post-traumatic stress disorder.[52] Equally, functional neuroimaging changes have been reported in the same conditions and in functional neurological disorder, irrespective of the presence of a TBI.[37–39] This complexity is not reliably accounted for in imaging studies of mTBI.