Confounding Factors in Postconcussive Disorders

Nathan D. Zasler

INTRODUCTION

The diagnosis of postconcussive disorders may be complicated by a number of confounding factors. The purpose of this chapter is to identify some of these issues and provide guidelines for addressing them. Even if a concussion (i.e., mild traumatic brain injury [MTBI]) is diagnosed based on neurological criteria at the time of an accident, one cannot necessarily conclude that symptoms ascribed to the event at the time of subsequent examination are in fact causally related nor, for that matter, that abnormal physical exam findings are attributable to the claimed concussive brain injury (CBI). The temporal onset of signs and symptoms, as well as their nature, severity, frequency, and response to treatment must be considered in assessing both causality and apportionment in the context of differential diagnosis after claimed MTBI. Clinicians need to consider all potential confounding issues that make assessing and managing this group of patients so challenging [1,2].

NOMENCLATURE

Cerebral concussion (Latin: commotion cerebri) is a phraseology that has been around since the time of Hippocrates. There remains some debate as to whether concussion and MTBI are analogous, although most clinicians and researchers do not make a clinical distinction. Some have advocated for avoiding the MTBI terminology altogether and instead classifying such injuries as CBI [3], avoiding the adjectival descriptor of mild. Others have advocated for dispensing with the nomenclature of “concussion,” as well as “postconcussion syndrome” due to their perceived unhelpfulness, and instead developing a unified classification of the severity of TBI coupled with a careful attempt to identify the underlying cause for any persistent posttraumatic symptom [4]. (See Chapter 6 for further details.)

The phrases “brain injury” and “head injury” are often used interchangeably, although these are two distinct terms. The former describes insult/trauma to the cerebrum and the latter connotes traumatic injury to the cranium or its surrounding structures.

A syndrome is a consistent set of signs and/or symptoms that occur together to define a condition; therefore, the use of the phrase “postconcussive syndrome” (PCS) is really a misnomer because the signs and symptoms that follow concussion are inconsistent across patients [5]. Postconcussion disorder (PCD) was introduced as a term in the fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV); however, there is a lack of evidence-based literature to support all the criteria endorsed in the definition and lack of consensus on the use of the definition outside of psychiatry. The phrase PCD is not found in DSM-5, which instead uses categories of mild neurocognitive disorder and major neurocognitive disorder to describe the degree of intellectual dysfunction associated with an array of conditions including TBI [6].

When postconcussive symptoms become a “syndrome” is unclear. The CDC defines a timeframe of 3 months for endorsing PCS; in ICD-10, PCS is defined as occurring when there is an injury “usually sufficiently severe to result in loss of consciousness” followed by an onset of at least three of eight symptoms within 4 weeks of the injury [7,8].

An extension of the PCS phraseology is the term “persistent postconcussion syndrome” (PPCS), which typically indicates that post-MTBI symptoms have persisted for longer than 6 months [9]; although some have suggested a 3-month criteria [10]. Like PCS, the designation of PPCS temporal onset is empirical. Recent writings have suggested an early phase of symptoms with a more organic basis and a late-phase symptom complex, which is highly influenced by a number of psychosocial factors and has little specificity for brain injury per se, although a history of multiple concussions seems to increase the risk of more severe and protracted symptoms [1,2]. The bottom line is that the longer symptoms persist after MTBI, the more likely it is that confounding factors are playing a contributory role above and beyond the original neurological injury [1].

DIFFERENTIAL DIAGNOSTIC ISSUES

The aim of evaluation following a claimed MTBI should be to appropriately understand the preinjury, injury, and postinjury history to facilitate accurate diagnosis. Thorough and appropriate differential diagnosis requires pursuing the potential etiologies for the presenting symptoms and/or signs while avoiding generic diagnoses for subjective complaints such as posttraumatic headache or dizziness, which provide no firm symptom or sign etiology or direction for appropriate treatment [1,4]. Understanding the myriad posttraumatic impairments that might produce symptoms attributed to concussion but that in fact have noncerebral origins is particularly important [1,2,5,11,12]. Conditions such as posttraumatic stress disorder (PTSD) and other anxiety disorders, depression, chronic pain, and insomnia, among others, can be misdiagnosed as PCS given the overlap of symptomatology. Good differential diagnosis is only possible with an eye to garnering sufficient historical information and performing an appropriate physical examination. Ideally, if feasible, corroboratory information should also be sought.

History

Obtaining a detailed history about preinjury, injury, and postinjury symptoms and signs can be very helpful in elucidating the true nature of the patient’s complaints and their accurate apportionment [1,2,4]. Evaluation of postconcussive symptoms poses a number of confounds in part due to the subjective nature and nonspecificity of the symptoms for MTBI; additionally, the common symptoms of concussion are fairly prevalent in the general population. In some cases, persistent symptoms appear to be an extension of acute symptoms that are taking longer than usual to resolve [1]. In other cases, pre-existing conditions or a prior history of problems that parallel postconcussive symptoms (e.g., dyssomnias, headache disorders, attentional problems, vertigo, tinnitus) may confound etiologic diagnosis and protract recovery.

Preinjury issues of relevance may include [1,2]:

• prior brain injury

• psychiatric impairment

• poor coping/resilience

• substance abuse

• ADD/ADHD

• learning disability

• headache disorders, for example, migraine

When apropos, preinjury medical and scholastic records including standardized testing should be requested for review and comparison.

Injury-related historical issues that should be explored by the examining clinician include [1,2,13]:

• The specifics of the incident responsible for the claimed MTBI (i.e., vehicular, fall, assault, sports injury) and details of same

• Memory for preconcussive and postconcussive events

• Any gap in memory and if present, its duration

• Any loss of consciousness and if present, its duration

• Any history of direct cranial impact injury

• History of neck injury

Postinjury history should seek to clarify symptom onset and progression/resolution, specific complaints experienced by the patient, evaluations and treatments to date including prior medications, dosing, and type of therapeutic treatments and response to same, as well as injury-related functional consequences and their evolution over time. An adequate history should be taken to explore for symptoms that may be consistent with physiological, vestibulo-ocular, and/or cervicogenic symptoms secondary to concussion, and/or associated injuries [14].

Physical Examination

Subtle neurological findings may be seen in persons after concussion, including smell or hearing loss, vestibular dysfunction, visual impairments such as convergence insufficiency, higher level balance impairment, kinetic tremor, slowed reaction time, and/or frontal motor impairments, among other potential findings [1,2,4,5,14]. The clinician should do a careful exam focusing on the patient’s known injury history and current somatic complaints. Examination should typically include an elemental neurological examination and some level of bedside cognitive-behavioral assessment along with musculoskeletal examination as pertinent [15].

Screening cognitive assessments should be considered when symptoms persist for more than a month and certainly when they have not cleared by 3 months to serve as a baseline for future comparison. When there are concerns about secondary behavioral impairments, standardized and normed psychoemotional batteries such as the MMPI-2, PAI, and MCMI-III should be considered [1,2,4,16].

Diagnostic Assessments

A few of the more commonly used and more sensitive testing approaches include neuroimaging (traditionally CT or MRI), electrophysiological (i.e., EEG), neuro-otological, neuro-ophthalmological, chemosensory, and/or neuropsychological testing. It is critical for clinicians to also understand the appropriate applications and limitations of such tests, including their validity (i.e., internal, external, ecological) and reliability (i.e., test–retest), as well as their sensitivity and specificity [2,5,17–19]. There is often over-reliance on diagnostics, in particular imaging studies, as a means of legitimizing claimed symptoms as MTBI-related, when in fact literature has demonstrated a lack of significant association between many such findings and postconcussive symptom report [20].

Pathologies That May Produce Signs and Symptoms Parallel to Those of MTBI

Cranial Trauma

Trauma to the cranium can produce an array of symptoms that parallel postconcussive symptoms without having any concurrent brain injury [1,2,3]. Some of the problems commonly seen after these types of injuries include headache, tinnitus, hearing loss, hyperacusis, vestibulopathies, olfactory impairments, and visual dysfunction.

Cervical Injuries

Injuries to the neck, such as through acceleration/deceleration or direct trauma, may produce an array of problems that may be mistaken for PCS, including referred cervicogenic headache, tinnitus, cervical vertigo, visual problems including blurry vision, autonomic dysfunction symptoms (including orthostatic hypotension) and photosensitivity, as well as retro-orbital pain [2,3,5,13,14].

Chronic Pain

Posttraumatic pain disorders are an often-overlooked concomitant of cranial and cervical trauma. When pain becomes chronic (i.e., more than 6 months duration), it typically becomes more challenging to identify the primary pain generators due to central sensitization phenomena, as well as secondary psychoemotional responses to chronic pain. Pain also tends to have adverse consequences on sleep and cognition, which further complicates both assessment and treatment [2,5,21,22].

Affective Issues

Patients often develop secondary psychological states after trauma. Clinicians working with such patients should be familiar with anxiety spectrum disorders including PTSD, depression, and adjustment disorders. Occasionally, patients may present with affective lability with a propensity to become easily tearful. Some have speculated that psychoemotional issues are predominantly responsible for persistent postconcussive symptom complaints beyond the 6- to 12-month mark, which would be another reason to intervene early to minimize, and ideally negate, secondary adverse psychoemotional responses to injury and losses [1,2,5,17,23].

Comorbidities

Patients often have multiple contributors to symptomatology following concussion. One cannot automatically assume that symptoms are attributable to a concussion [1,2,4,5,17] or for that matter to the injury in question. Many of the comorbid conditions associated with concussion have been shown to protract recovery after this type of injury including PTSD/anxiety disorders, depression, pain (cervicocephalic pain, in particular), and sleep disorders, among others [2,5,21,24].

IATROGENESIS

The phenomenon of iatrogenesis can work in two directions, neither of which, ultimately, is in the best interest of the patient. Doctors who dismiss symptoms that are truly neurological following MTBI do the patient a potentially great disservice by further promulgating the potential for adverse adaptive responses, including anxiety, depression, insomnia, stress, and worsening of pain, which will likely result in protraction of impairment and any related functional disability [1,2,4,16,24]. On the other hand, clinicians who over-diagnose concussion-related impairments may actually be producing a nocebo effect; that is, they are instilling negative expectancies, which may ultimately manifest into maladaptive behaviors, reinforce disability (which in fact may not be present), and perpetuate inappropriate diagnostic labels, as well as lead to ineffective and clinically unnecessary, as well as often costly treatments [1,2,4,25–27].

OTHER FACTORS TO CONSIDER

Clinicians should be aware of the literature examining the impact of preinjury personality (including resilience, coping skills, and stress tolerance), psychosocial factors, and litigation on symptom reporting, clinical presentation, prognosis, and treatment response [28–31]. An important but often ignored area of clinical and neuropsychological assessment is that of effort and response bias testing. Effort testing is important to assure that both symptom and performance validity are acceptable [32–34]. In the context of postconcussion assessment, response bias testing allows the practitioner to determine the response style of the patient relative to whether they are providing unbiased responses or coloring them in a particular direction (i.e., symptom minimizing versus symptom magnifying). In this latter context, practitioners need to be aware of how factors such as psychosocial and preinjury psychiatric problems, expectancy effects, postinjury stress, litigation, good-old-days bias, stereotype or diagnosis threat [35–37], and postinjury psychological factors may affect both response style and effort in order to fully evaluate the validity of interview data and diagnostic testing results [37–39].

Patients may fear that they will have permanent brain damage (assuming they have brain damage or dysfunction at all), which may worsen the original symptoms secondary to the aforementioned nocebo effect. Preoccupation with the injury may be accompanied by the assumption of a “sick role” and hypochondriasis. Legal proceedings, including social security disability cases, worker’s compensation claims, and personal injury litigation can promulgate this focus and maintain illness behavior [1,38].

The concept of diagnosis threat [39] as related to negative expectations on cognitive performance after MTBI, as first posited by Suhr and Gunstad [39], involves the hypothesis that focusing on the fact that someone had an MTBI and/or on the consequences of the same, may in and of itself lead to worse performance on testing compared to the patient for whom the consequences of this injury are not a focus [1,37,39]; however, some recent studies have called this into question [40,41].

CONCLUSIONS

Practitioners must take an array of confounding variables into consideration when assessing and treating persons following concussion. Comprehensive assessment of preinjury, injury, and postinjury history, and a well-informed knowledge of concussion guidelines and current MTBI science will result in optimizing diagnostic accuracy and treatment outcomes.

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