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.

Current Terminology and its Weaknesses

Numerous definitions for mTBI have been published (Table 1).^[3–13] The definitions extrapolate the presumed presence and severity of an underlying TBI from clinical markers. Alteration of mental state is considered a fundamental marker of TBI, with classifications agreeing, for example, that loss of consciousness is sufficient (but not necessary) to diagnose a mTBI. However, debate remains regarding the degree of alteration in mental state required, whether evidence of structural injury constitutes a more severe injury and whether the presence of subjective post-injury symptoms (e.g. headache, dizziness, cognitive impairment) is sufficient to diagnose a TBI.

A recent survey of mTBI experts found agreement amongst the panel that individuals with an mTBI can present with isolated subjective symptoms such as headache, dizziness and cognitive impairments.^[4] However, such symptoms are not specific to head injury, occurring at the same rate in those with extracranial injury and in up to three quarters of otherwise healthy adults.^[14–16] This perhaps explains the finding that 59% of the general population who report having been 'concussed' deny ever having had a brain/head injury.^[17]

Despite the lack of specificity of these symptoms to brain injury, the term 'PCS' is widely used to describe the persistence of these symptoms beyond 3 months following mTBI. Perhaps in recognition of this lack of specificity [there was only 40% agreement between the 4th edition of the Diagnostic and Statistical Manual (DSM-4) and 10th edition of the International Classification of Disease (ICD-10) diagnostic criteria for PCS when applied to a large cohort],^[18] the latest iterations of the DSM and ICD have removed the category of PCS and subsumed it under 'neurocognitive disorders due to traumatic brain injury' and 'mild neurocognitive disorder' (which can be secondary to trauma), respectively (Table 2).

Unfortunately, the criteria for neurocognitive disorder continue to lack diagnostic precision and focus on non-specific symptoms. The aim should be objective diagnostic measures to help categorize the symptoms within specific diagnoses, that in turn might link to specific treatments. In the differential diagnosis section of neurocognitive disorders due to TBI in DSM-5, the practitioner is advised specifically to consider alternative diagnoses of somatic symptom disorder or factitious disorder to explain the persistent neurocognitive impairment. The Scottish Intercollegiate Guidelines Network (SIGN) for brain injury rehabilitation states: 'In a small minority of mTBI patients, symptoms may be more prolonged, but in such cases the determinants of disability appear to be personal and social factors and not related to the brain injury.^[19] This approach results in a clear dualistic split between an (unspecified) physical damage-related mechanism for persistent symptoms and an (unspecified) psychological mechanism. However, as detailed below, a variety of interacting mechanisms for symptoms may exist which span the false divide between 'physical' and 'psychological'.

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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.