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

Disclosures

Brain. 2022;145(6):1906-1915.

Diagnoses That may Underpin Persistent Symptoms After Mild Traumatic Brain Injury

The foundation of our approach to persistent symptoms after mTBI is the recognition that the symptoms are non-specific. This means that, in different people, there might be a range of possible diagnoses within which such symptoms could cluster. Alternatively, numerous different underlying diagnoses might be present in another individual with the same persistent symptoms and those symptoms may have a high degree of overlap between diagnoses. The assessment therefore needs to tease apart (or indeed cluster together) symptoms to establish a reasonable diagnostic formulation shared with the patient, with the express purpose of developing a rational bio-psycho-socio-ecological treatment plan informed by that formulation.^[53] To illustrate this approach, we have used two of the most commonly described symptoms after mTBI; headache and dizziness (Figure 1).^[54]

(Enlarge Image)

Figure 1.

Two distinct approaches to the same symptom complex post mTBI. (A) Panel demonstrates the consequence of the PCS label being applied, resulting in a single non-specific treatment. (B) Adopting an individualized diagnostic formulation to consider and identify the multiple potential causative factors potentially underlying identical symptom complexes. The consequence is the instigation of targeted evidence-based individualized treatment plans. Dotted arrows represent contributory processes to symptom persistence/amplification.

When compared to primary headache disorders, post-traumatic headache most commonly represents a migraine-type headache with associated migraine symptoms, including nausea, light and noise sensitivity, irritability and cognitive symptoms—symptoms that are also listed as typical symptoms of PCS itself.^[55] Furthermore, a pre-existing or family history of migraine are risk factors for prolonged post-traumatic headache.^[56,57] However, although migraine and post-traumatic headache pathophysiology may overlap in some patients, there is likely to be a range of pathophysiological processes underpinning post-traumatic headache and treating all the same is unlikely to be successful.^[58] For example, persistent psychological factors and medication overuse are recognized to prolong post-traumatic headache.^[59] Therefore, treatment trials that fail to stratify patients and instead treat all post-traumatic headache as the same are at risk of failure. Despite these caveats, early treatment of post-traumatic headache, particularly in those at greatest risk, and a diagnostic explanation for the patient including the clustering of other 'postconcussional' symptoms are warranted.

Post-traumatic dizziness is another good example of symptom clustering. The commonest causes following mTBI are benign paroxysmal positional vertigo (40%) and vestibular migraine (34%).^[60] Vestibular migraine is associated with other migrainous symptoms as discussed above but, perhaps surprisingly, benign paroxysmal positional vertigo is also associated with cognitive impairments and heightened anxiety, especially if left untreated.^[61]

Relationship to Psychiatric Disorders

Mild TBI increases the risk of developing a subsequent psychiatric condition nearly threefold.^[62] However, trying to distinguish psychiatric conditions such as anxiety, depression or post-traumatic stress disorder from the effects of a mTBI can be challenging due to symptom overlap, yet has important implications for symptom persistence (Table 3).^[54,63,64] It is important to remember that symptom overlap can obscure diagnostic clarity, 50% of people with depression who have not had a TBI meet the criteria for moderate to severe PCS.^[65] Alongside the psychosocial impact of head injury, it is of course also possible for depression and anxiety to be related to structural brain injury, either as a result of macroscopic damage or triggering of a secondary inflammatory process.^[66–68]

There also remains stigma surrounding mental health diagnoses, which results in a higher likelihood of misattributing the cognitive changes to the injury, rather than potentially reversible psychological or psychiatric causes. The unfortunate consequence of this is that appropriate, evidence-based treatment may not be accessed in a timely way, subsequently worsening the treatment responsiveness and prognosis of the psychiatric condition.

Functional Neurological Disorder and Somatic Symptom Disorder

Functional neurological disorder is characterized by internal inconsistency, typically demonstrated by the complaint of abnormal function in a system that can be demonstrated (usually clinically, but sometimes by investigation) to be capable of normal function.^[69] Over 80% of people with functional neurological disorder report a health event near to the onset of functional symptoms.^[70] These events, which include accidental injuries, are typically minor and would be expected to improve and not produce lasting symptoms in their own right.

This preceding discussion clearly has relevance for the development of persistent symptoms after mTBI. The immediate and lasting physical and psychological consequences of accidents and injuries causing TBI could undoubtedly act as triggers to the onset of functional neurological disorder and/or somatic symptom disorder in some people, also interacting with pre-morbid risk factors and subsequent behaviours such as fear avoidance.^[71] Positive diagnosis of such symptoms is possible within normal clinical practice, and diagnostic explanation according to best practice is typically a positive and empowering experience for patients.

Medicolegal Impact

Medicolegal processes appear to be correlated with persistence of symptoms in some people, a finding that is often interpreted as evidence that mTBI is psychological in nature.^[72] The fact that there is often someone at fault or to blame, resulting in adversarial circumstances between involved parties, means that primary psychological reactions are naturally triggered by the litigation process, such as loss aversion, anger or revenge. The financial implications in this context are not necessarily the motivator for the feigning behaviour.^[73,74] It is notable that often from the outset of the medicolegal process, the injury might not be acknowledged by the other party. This can result in anger from the injured individual, particularly if they are subject to independent assessments where the assumption is that they are not injured at all, or perhaps not as severely as thought, or even that they are malingering.^[73] These effects translate into an increased likelihood of feigning behaviour as a behavioural expression of the emotional sequelae of the mTBI or the need for revenge if trust is violated.^[75]

Miscellaneous Factors

In addition to the above causes, it is important to consider the potential effect of non-brain injury factors. For example, extracranial injuries influence symptom persistence.^[76] This may be related to effects on sleep, pain and psychological impact. Finally, medications commonly prescribed after traumatic injuries, particularly opiate based analgesics, can impair cognitive functions, disrupt sleep and cause dizziness and nausea.

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Next Section

Abstract and Introduction
Current Terminology and its Weaknesses
Approaching Mild Traumatic Brain Injury as an Interface Disorder
Diagnoses That may Underpin Persistent Symptoms After Mild Traumatic Brain Injury
Recommendations on how to Implement Assessment and Treatment
Conclusions
References

Table 1. Key definitions of mTBI and concussion
Criteria (year)	Definition of head injury	Factors related to injury can include
Centers for Disease Control and Prevention (2003)⁷	Blunt trauma to head or acceleration/deceleration forces results in a brief alteration of mental status or brief loss of consciousness	GCS 13–15, LOC < 30 min; PTA ≤ 24 h; non-penetrating cranio-cerebral injury.
WHO (2005)⁶	Acute brain injury resulting from mechanical energy to the head from external physical forces.	GCS 13–15^a, LOC ≤ 30 min; PTA < 24 h; and/or other transient neurological abnormalities,^b,c and intracranial lesion not requiring surgery.
Mayo (2007): mild (probable) TBI¹²	Traumatically induced injury that contributed to physiological disruption of brain function	GCS 13–15 (≥13 at 30 min); LOC momentary to 30 min; PTA momentary to 24 h; skull fracture with intact dura; EXCLUSION if death due to TBI, worst GCS in first 24 h < 13^c, abnormal head CT.
Mayo (2007): symptomatic (possible) TBI¹²	Traumatically induced injury that contributed to physiological disruption of brain function	Symptoms only^d. Symptoms must not be attributable to pre-existing or co-morbid diagnoses. EXCLUSION if criteria met for mild probable TBI.
Department of Veterans Affairs/Department of Defense (2009)⁸	A traumatically induced structural injury and/or physiological disruption of brain function as a result of an external force	GCS 13–15^e; LOC momentary to 30 min; alteration of consciousness/mental state (AOC) momentary up to 24 h; PTA < 24 h; neurological deficits^f that may or may not be transient; normal structural imaging.
Ontario neurotrauma (2018)^11,g	Concussion/mTBI denotes the acute neurophysiological event related to blunt impact or other mechanical energy applied to the head, neck or body (with transmitting forces to the brain), such as from sudden acceleration, deceleration or rotational forces	LOC < 30 min; any AOC at the time of the injury; PTA ≤ 24 h; physical symptoms^h; normal standard imaging.
American congress of rehabilitation medicine (2021)⁴	A traumatically induced physiological disruption of brain function	Symptoms following a head impact, without associated observable signs (in some instances), Recommendation (i) consider a probabilistic framework that weighs observable signs more than subjective symptoms and (ii) incorporate objective cognitive, balance and vestibular-oculomotor test findings. 1993 criteria^c: initial GCS 13–15; any LOC; any AOC at the time of the injury and focal neurologic deficit(s) that may or may not be transient; any PTA.
1st International conference of concussion in sport (2002)¹³	A complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces.	(i) Direct blow to the head, face, neck or elsewhere on the body with an 'impulsive' force transmitted to the head. (ii) Rapid onset of short-lived impairment of neurological function that resolves spontaneously. (iii) May result in neuropathological changes, but the acute clinical symptoms largely reflect a functional disturbance versus structural injury. (iv) Results in a graded set of clinical syndromes that may or may not involve LOC. Resolution of the clinical and cognitive symptoms typically follows a sequential course. (v) Typically grossly normal structural neuroimaging studies.
5th International conference of concussion in sport (2017)⁵	Sports-related concussion is a TBI induced by biomechanical forces	Modifications to the above: (i) In some cases, signs and symptoms evolve over a number of minutes to hours. (ii) No abnormality is seen on standard structural neuroimaging (iii) Sports-related concussion results in a range of clinical signs and symptoms.^c In some cases symptoms may be prolonged.

AOC = alteration of consciousness; GCS = Glasgow coma scale; LOC = loss or decrease of consciousness; PTA = post traumatic amnesia, any loss of memory for events immediately before or after the accident.
^aIdeally at 30 min post injury or first opportunity presented to healthcare.
^bSuch as focal signs or seizure.
^cThe clinical signs and symptoms cannot be explained by alternate cause, e.g. drugs or other comorbidities (e.g. psychological factors or coexisting medical conditions).
^dBlurred vision, confusion (mental state changes), dazed, dizziness, focal neurologic symptoms, headache or nausea.
^eBest available score <24 h.
^fWeakness, loss of balance, change in vision, praxis, paresis/plegia, sensory loss or aphasia, etc.
^gStratified into high and low risk mTBI.
^hVestibular, headache, weakness, loss of balance, change in vision, auditory sensitivity or dizziness.

Table 2. Current definitions of persistent symptoms post head injury
	Timing	Trigger	General	Physical	Emotional	Cognition
Postconcussional syndrome (ICD-10)	Chronic, permanent or late emerging.	Head injury usually with loss of consciousness.	Not explicitly specified.	Headache, dizziness, fatigue, insomnia.	Irritability, reduced tolerance to stress, emotional excitement and alcohol.	Difficulties with concentration, memory and mental tasks.^a
Mild neurocognitive disorder (ICD-11)	<1 month between head injury and symptom onset.	Head injury with loss of consciousness or aetiology may be undetermined.	Not sufficiently severe to significantly interfere with independence or activities of daily living.	Headache, dizziness, fatigue, insomnia, noise intolerance.	Irritability, reduced alcohol tolerance, depression, anxiety, emotional lability, preoccupation with symptoms.	Subjective decline in concentration, memory, or intellectual difficulties.
Major/mild neurocognitive disorders due to TBI (DSM-5)	From injury or when consciousness recovers. Persists beyond acute period. Resolution: usually complete and <3 months.	Head injury.	Severe versus modest interference with ability to be independent in functions of daily living.	Headache, vertigo, sleep disorder, tinnitus, hyperacusis, photosensitivity, anosmia, hemiparesis, seizures, visual disturbance, orthopaedic injury, cranial nerve or neuromotor deficits.	Irritability, reduced tolerance to psychotropic medication, loss of emotional control (e.g. aggression), inappropriate affect, apathy, anxiety, depressed mood,^b altered personality and/or social cognition.	Difficulty concentrating, learning and memory, executive function, slowed processing speed, reduced cognitive efficiency, decline in language, neglect, constructional dyspraxia.

^aPersistent disorientation and confusion (compare post-traumatic stress disorder with specific triggers).
^bDepressive and anxiety symptoms amplify cognitive complaints and worsen functional outcome.

Table 3. Diagnoses and important differentials for persistent symptoms post head injury from DSM-5
	Timing	Trigger	General	Physical	Emotional	Cognition
PTSD^a	>1 month of persistent symptoms With delayed expression: Full symptom expression >6 months after event.	Actual/threatened harm including head injury.	Impaired social, occupational and other aspects of functioning.	Disturbed sleep (e.g. recurrent distressing dreams related to trauma), change in arousal, hypervigilance for potential threats, episodic physical symptoms can act as trigger for PTSD symptoms.^b	Irritability, outbursts, recklessness, flashbacks, intense/prolonged distress related to cues with/without avoidance, persistent negative emotional state.	Difficulty concentrating, inability to remember important aspects of event (not due to head injury), recurrent distressing memories (consider obsessive compulsive disorder criteria for obsession if unrelated to trauma).
Generalized anxiety disorder	Persistent symptoms for more than 50% of the time for >6 months.		Impaired social, occupational and other aspects of functioning.	Disturbed sleep, fatigue, exaggerated startle, muscle tension or soreness, change in arousal including panic attacks, somatic symptoms e.g. sweating, diarrhoea.	Irritability, anxiety/fear not related to traumatic event or specific triggers, overestimate dangers/future threat with avoidance, worry about multiple events, situations or activities.	Difficulty concentrating owing to worrisome thoughts, mind going blank.
Major depressive disorder	>2 weeks duration of new or clearly worsened symptoms, can be discrete episodes.	Can be traumatic/stressful event, often on a background of adverse childhood experiences.	Impaired social, occupational and other aspects of functioning.	Sleep disturbance, fatigue, weight change, loss of libido, general heaviness of limbs,^c somatic symptoms especially pain,^d psychomotor agitation or retardation.	Irritation, ^e outbursts, excessive guilt/worthlessness , low/dysphoric mood or anhedonia , diminished interest, suicidal thoughts, anxiety, phobias, excessive worry.	Difficulty concentrating, thinking, distractibility, indecisiveness, obsessive rumination (compare PTSD where related to a specific event).
Functional neurological disorder	Acute: <6 months duration (may have similar previous episodes). Persistent: >6 months.	Onset may be preceded by injury (physical/psychological).	Impaired social, occupational and other aspects of functioning.	Disturbance of any neurological system, internal inconsistency on examination.	Can be associated with dissociative symptoms at onset or during attacks, distress associated with loss of function.	Absent from definition.
Somatic symptom disorder	Any one symptom may not be persistent but state of being symptomatic >6 months.	Can be precipitated by stressful life events	Symptoms are distressing or result in significant disruption of daily life.	May represent normal bodily sensations/discomfort, may be specific (e.g. localized pain) or generalized (e.g. fatigue).	Persistently high levels of anxiety related to symptom and/or family history of disease, appraise bodily symptoms as threatening.^f	Excessive thoughts related to somatic symptom (thoughts are less intrusive than obsessive compulsive disorder).

PTSD = post-traumatic stress disorder.
Within symptom columns: bold denotes useful differentiating features; italics denotes shared symptoms across more than one category.
^aMore than 80% likely to have symptoms that meet diagnostic criteria for another mental disorder eg depression, bipolar disorder, anxiety, substance use compared to those without PTSD.
^bNew onset of somatic symptoms within the context of posttraumatic distress may indicate PTSD rather than a functional neurological disorder.
^cVersus focal and more prominent in functional neurological disorder.
^dDepression single diagnosis if somatic symptoms and related thoughts, feelings or behaviours occur only during major depressive episodes.
^eIf mood disturbance characterized by irritability alone in the absence of sadness/anhedonia consider alternative diagnoses, e.g. attention deficit hyperactivity disorder.
^fAnxiety is focused on symptoms and distress caused by the symptoms (cf. generalized anxiety disorder). Absence of repetitive behaviours aimed to reduce anxiety that occur in obsessive compulsive disorder.