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.

Abstract and Introduction

Abstract

Persistent symptoms following a minor head injury can cause significant morbidity, yet the underlying mechanisms for this are poorly understood. The shortcomings of the current terminology that refer to non-specific symptom clusters is discussed. This update considers the need for a multi-dimensional approach for the heterogenous mechanisms driving persistent symptoms after mild traumatic brain injury. Relevant pathophysiology is discussed to make the case for mild traumatic brain injury to be conceptualized as an interface disorder spanning neurology, psychiatry and psychology. The relevance of pre-injury factors, psychological co-morbidities and their interaction with the injury to produce persistent symptoms are reviewed. The interplay with psychiatric diagnoses, functional and somatic symptom disorder presentations and the influence of the medicolegal process is considered. The judicious use and interpretation of investigations given the above complexity is discussed, with suggestions of how the explanation of the diagnostic formulation to the patient can be tailored, including insight into the above processes, to aid recovery. Moving beyond the one-dimensional concept of 'postconcussional syndrome' and reframing the cause of persistent symptoms following mild traumatic brain injury in a bio-psycho-socio-ecological model will hopefully improve understanding of the underlying contributory mechanistic interactions and facilitate treatment.

Introduction

Traumatic brain injury (TBI) is common. Fortunately, the vast majority of injuries are mild, typically causing transient, self-limiting symptoms and no long-term sequelae. However, approximately 20% of people report persistent symptoms at 3 months post-injury following mild TBI (mTBI). For these people, the long-term outlook is poor, with many experiencing ongoing negative impact on work and social function.^[1,2] Given how common mTBI is, this represents a huge number of affected individuals.

Persistent symptoms that occur after mTBI are likely to be due to a range of identifiable disorders, many of which have evidence-based treatments. However, we argue that clinical and research practice has been held back by the use of syndromic terms such as postconcussional syndrome (PCS) to categorize patients. Clinically, it produces bias away from considering treatable underlying causes of symptoms. From a research perspective, it fosters an assumption that people with such symptoms are a single group pathophysiologically. However, we would argue that the diagnostic heterogeneity here means that group data from, for example functional MRI studies, are unlikely to provide a valid source of information to make inferences about mechanisms of symptoms, nor to extrapolate from, in order to determine new avenues for treatment development.

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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.