Post-traumatic headaches and vision: A review

1 Introduction

The United States Center for Disease Control (CDC) reports that traumatic brain injury (TBI) in the USA amounts to 2.5 million emergency room visits, admissions to hospital and deaths annually (Prevention, 2015). Of these patients, over 75% have normal conventional imaging (i.e., CT or MRI) and are subsequently labeled as “mild traumatic brain injury” (mTBI). Furthermore, CDC also reports that more than 90% of these mTBI patients suffered “blunt trauma” sustained during motor vehicle accidents (MVA), falls, assaults and sport-related activities. The most common symptomatic sequela of mTBI is headache, estimated to have an incidence as high as 90% (AFHSC, 2013). It is important to note that not only is the definition of “mild” TBI not universally accepted, but also that the “mild” aspect mainly speaks to the absence of findings on conventional imaging (GL, 2006; Williams, 1990), and not that the injury itself is mild. Mild TBI events can certainly cause long lasting, pervasive, and disabling health problems. Indeed, the lack of structural deficits on conventional imaging does not rule out functional deficits demonstrable on physical examination as per the current NIH definition (GL, 2006), e.g., oculomotor dysfunction (OMD) or indirect traumatic optic neuropathy (ITON). The current NIH definition states: “A person with a mild TBI may remain conscious or may experience a loss of consciousness for a few seconds or minutes. Other symptoms of mTBI include headache, confusion, light-headedness, dizziness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue or lethargy, a change in sleep patterns, behavioral or mood changes, and trouble with memory, concentration, attention, or thinking”. It is noteworthy that the section on vision is quite vague (i.e., “tired eyes”). In fact, studies on mTBI have shown an incidence of OMD as high as 69% for having at least one deficiency of saccades, accommodation, convergence deficits and smooth pursuits (Master, 2016).

The development or worsening of headaches after a head injury is even more pronounced in certain populations such as active military service members. Over 98% of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans with TBI reported headaches; 37% reported headaches lasting longer than 3 months (Theeler, 2010). Twenty seven percent of soldiers in this same study reported headaches on an on-going chronic basis. However, only approximately half of these headaches meet the diagnostic criteria for post-traumatic migraine headaches (PTMH), leaving questions about the nature of the remaining headache types. These more chronic symptom trajectories must not be dismissed as they may contribute to the 3x-higher rate of suicide in mTBI patients compared to the general population (Fralick, 2016). One of the most tragic statistics in this research, which examined suicide rates in the post-concussion population using a large sample size (more than 235,000), was that over 50% of those who committed suicide had a documented visit with a physician within the last week of life. In fact, over time it was reported also that these suicide rates exceeded the rates of suicide in the general (non-mTBI and mTBI) armed forces. This finding should be a call to healthcare professionals to listen carefully to the symptoms of mTBI patients with caution to avoid dismissing any as “frivolous” or “idiopathic”. Sadly, patients often do not have the vocabulary to express many of their symptoms, hence the rather nebulous term “tired eyes” in the NIH description cited previously. While it is known that visual symptoms present frequently after mTBI and patients are often found to demonstrate disorders listed above, patients might only describe vague complaints such as difficulty reading, or eyes not working together or simply “discomfort around the eyes” (Kontos et al., 2020; Lovell, 2004). The peri-ocular and ocular headache that might be described as a “pressure feeling around the eyes” was seen with more than a 10-fold rate in concussed athletes compared to controls (Poltavski, 2014).

Functional visual difficulties can often be improved with appropriate visual rehabilitative interventions (Ciuffreda, 2016; Gallaway, 2017; Thiagarajan, 2–14, 2014; Thiagarajan, J.E.; Ludlam, Kapoor, 2014; Widmer, 2018), thus heightened awareness by both physicians, optometrists, physical therapists and other allied healthcare professionals is necessary. In our experience, appropriately qualified optometrists and ophthalmologists are often those providers more likely to identify OMD in concussion and recommend rehabilitation directed at this concern, something undertaken for the most part by optometrists with advanced training in the area. The need to direct patients to these providers has also been expressed by other professions who treat concussed patients such as otolaryngologists, psychiatrists, and sports medicine providers (Marshall, 2015; Matuszak, 2016; Park, 2019).

Recent research on inter-disciplinary care of mTBI (Kontos et al., 2020) has shown that of the six global vectors of symptomatology (i.e., migraine, ocular, vestibular, cervical, sleep and cognitive/psychological), migraine was most common followed by ocular symptoms. Furthermore, the highest correlations between symptom areas were found between ocular-migraine followed by ocular-cognitive. Finally, the two highest areas in terms of ability to differentiate controls from mTBI (using Receiving Operator Characteristic / ROC) analysis were migraine and ocular, respectively. This supports the notion that consideration of visual symptomatology is vital when treating mTBI patients with on-going symptomatology in general, and for those with visual symptoms, in particular when headaches are also reported.

Recognizing that at least 40% of the primate brain subserves vision (Felleman, 1991) and that both cortical and sub-cortical areas of the brain are heavily involved in processing visual information, it seems most reasonable to engage in a robust discussion of the confluence of headache, mTBI and vision. Given the pervasiveness of both photophobia and peripheral visual motion hypersensitivity symptoms (often described by our patients as “visual overwhelming”) in mTBI cases (Singman E.L.; Quaid, 2019), it appears logical to discuss global visual motion processing mechanisms both from direct magnocellular pathways and indirect superior colliculus / pulvinar pathways, converging to regions such as the middle temporal Area (MT/V5) (Born, 2005). Area MT/V5 is believed to be part of the dorsal stream of visual processing, sometimes referred to as the “where pathway”, i.e., that pathway associated with motion and location, as opposed to the ventral stream, referred to as the “what pathway”, i.e., that pathway associated with form recognition. It seems reasonable to suggest that photophobia might involve pathways similar to peripheral visual motion because M-cells, i.e., retinal ganglion cells that project to the magnocellular layers of the primate lateral geniculate nucleus are much more sensitive to luminance contrast than P-cells which project to the parvocellular layers and also that M-cells mediate the dorsal stream, whereas P-cells mediate the ventral stream (Digre & Brennan, 2012; Purpura, Kaplan, & Shapley, 1988).

2 Headache after head trauma through the lens of vision

We will discuss specific vision issues and their connections to headaches following the classification system of the International Headache Society (IHS), known as ICHD-III (International Classification of Headache Disorders, 3^rd Edition). It is vital to note that the terms primary and secondary headache should be understood in the context of the ICDH-III. If a patient develops a new headache, which occurred for the first time, and this situation has a close temporal relation to another disorder known to cause headache, the new headache is coded as a secondary headache attributed to the causative disorder. This remains true even when the headache has the characteristics of a primary type headache (i.e. migraine, tension-type or cluster headache). This is important to keep in mind in the context of mTBI, as many patients have no history of headaches prior to the reported mTBI event.

Note that the layout of this review will purposefully mirror the order of the classification of the ICHD-III to ensure consistency with the International Headache Society ordering and facilitate cross-referencing.

3 Part I: Primary headaches

4 Part II: Secondary headaches

5 Part III: Neuropathies & facial pains and other headaches

6 Discussion

Given that vergence, accommodation, pursuit and saccadic-eye movement deficits are (i) common in mTBI and (ii) are not related to eye pathology per se, we would posit that the term “ ocular ”, mentioned above in reference to screening tools employed to inform a multidisciplinary approach (Kontos et al., 2020) might more appropriately be replaced with the term “ vision ”; terminology matters greatly. We think of the term “eyesight” as pertaining to visual acuity, visual field, color vision, etc. Furthermore, the term “ocular” refers to the globe itself and, while certainly appropriate for ocular disease related issues, is not actually an adequate descriptor for the innervational (as opposed to mechanical) oculomotor deficits listed above. On the other hand, we think of the term “vision” as referring to an entire visual process including the neural processing of afferent and efferent visual information, visual memory, etc., a far more complex activity.

Our semantic approach is similar to the rationale for the nomenclature used in the vestibular aspect of TBI (i.e., central/brain-related deficit versus peripheral/end organ-related deficit). In mTBI, the “eyeball itself” is often healthy with some exceptions (e.g., ITON (Singman; Daphalapurkar, 2016)), but there are very frequently oculomotor problems. The archetypal deficit might be convergence insufficiency (CI), which is estimated to be demonstrated in as many as 49% of TBI patients (Barnett, 2015; Vernau, 2015). In CI, the patient has full adduction towards the nose monocularly, yet cannot converge when both eyes are engaged, thereby ruling out a myogenic defect. Notably, evidence suggests that convergence is not innate, but rather only starts to develop at 4 months post-birth with full peak normal vergence occurring by 5–6 years of age (Weinacht, 1999). Fusional mechanisms that support convergence certainly require intact ocular and orbital tissues but also need the development of more complex central structures. There are many serial systems involved vergences; the midbrain appears to be a key relay station of the subservient pathways via networks to the cerebellum and pons (Gamlin, 2002), area V1 (Trotter, 1996), MST (Middle Superior Temporal) cortex (Takemura, 2001) and Frontal Eye Fields (FEF) (Gamlin, 2002). It is probable that diffuse axonal injury (DAI) resulting from TBI might affect multiple locations along this complex network (Thiagarajan, D.P., 2011). Although this makes determining the exact location of injury difficult in terms of a diagnosis of deficient vergences, it does support the idea that vergence deficiency is a sensitive clinical indicator of concussion.

The vestibular-ocular reflex (VOR) can also become deranged after TBI despite the absence of evident damage to the eye or inner ear, i.e., the ocular and vestibular end organs, respectively. Indeed, the central processes supporting the VOR appear to be quite susceptible to damage after TBI, manifesting as dizziness with head and/or eye movements in many patients (Herdman, 2014).

A key central processor for visual motion detection and responsiveness is Area MT/V5, one of the very few visual areas almost fully myelinated at birth (Gilaie-Dotan, 2016). Area MT receives a substantial thalamic magnocellular input, which in turn receives major input from peripheral retina, i.e., that portion of the retina enabling motion processing, flicker perception and contrast gain (Born, 2005; Derrington, 1984). This pathway permits area MT to function as a significant contributor to visual motion processing. Indeed, Area MT is so critical to gross motor development in infants that global motion perception can be used to aid in the evaluation of dorsal visual stream function in early childhood (Thompson, 2017). Notably, symptoms of fluorescent lighting- and peripheral motion-intolerance as well as photophobia are frequent patient complaints after mTBI, supporting the idea that Area MT (or, at least, dorsal visual stream function) is particularly susceptible to damage after head trauma.

It should be mentioned that the vestibular system is also fully formed at birth (D.J., 2012). The contemporaneous and early development of a mature Area MT and a mature vestibular system at birth permits the VOR to support an infant’s ability to “orientate in space”. Specifically, the robust VOR represents the confluence of the infant brain’s efforts to employ two significant sensory systems in an integrated manner. This integration determines the infant’s sense of “where” (i.e., where am I and where is everything around me) weeks or even months before the fully matured sense of “what” (i.e., what are those images and colors mean). Furthermore, the substantial motion-dominated magnocellular input to Area MT (Bourne, 2006; Gilaie-Dotan, 2016) lays the foundation for a stable platform upon which the development of fine central vision depends.

In the context of headaches after mTBI, it is known that patients commonly report headache when trying to sustain stable gaze or perform saccades, functions subserved by Area MT. They also report painful intolerance to perceiving motion stimuli or performing rapid head turns, functions subserved by VOR integration. These frequent symptoms become a challenge for the clinician because the vestibular system often must be assessed indirectly via the visual system, i.e., through the examination of eye movements. Therefore, headaches secondary to oculomotor dysfunction can result in ambiguity during VOR assessment if not properly identified prior to vestibular testing (Mantokoudis, 2016; Singman; Quaid, 2019). As mentioned previously, these ocular (we prefer “ vision ”) post-TBI headaches (i.e., “tired eyes”) are not readily captured in current headache classifications. Therefore, we suggest that headaches related to oculomotor dysfunction after TBI be included in above-mentioned IHC-3 Part III(14) section, i.e., headache from somewhere else in the brain, until such time as the location of damage and origin of headache is clarified.

Another subject begging clarification concerns the effect of light on patients with TBI. Main & Dowson (2000) reported that short and long wavelengths lowered the discomfort thresholds in migraineurs during the interictal period. Blue light may cause damage to the cornea lens and retina and yet may be critical for refractive development and regulating circadian rhythm (Zhao, 2018). A recent randomized controlled trial demonstrated that patients with mTBI enjoyed significantly better sleep patterns after blue light exposure (469nm) compared to placebo (Killgore, 2020). While this paper did not look at photophobia specifically in migraine, the authors have noted anecdotally in their clinics, that blue tints in post concussion syndrome patients appear to reduce photophobia and hypersensitivity to high contrast motion in peripheral gaze (i.e., OKN drum). It is difficult to reconcile the conflicting data and there are likely a number of confounding variables such as the contribution of dry eye to photophobia and migraine (Diel, Kardon, Buse, Moulton, & Galor, 2021), as well as the degree to which intensity rather than wavelength plays a role (Zivcevska, 2020). The distribution and density of photoreceptors in the human retina is highly variable (Curcio, 1990; Roorda, 1999). Short wavelength cones (peak absorbance 420nm) are relatively absent in the foveola suggesting they stimulate processes associated with peripheral vision. Furthermore, area MT neurons, while receiving input from all 3 cone types, respond in a directionally selective manner to S cones (Seidemann, 1999), consistent with the idea that S cones are involved in motion detection, i.e., peripheral rather than central visual processing, or the “where” rather than the “what”. Presuming the visual pathways of the MT area are damaged after concussion and that this damage underlies the photophobia and peripheral motion intolerance experiences by concussed patients, then one could hypothesize that stronger or more enriched S-cone stimulation might recruit greater activity in an MT pathway made somehow deficient by TBI and offer some symptomatic relief.

7 Conclusions

Every type of headache can be initiated or worsened after head injury. Furthermore, the visual system is very likely to be affected directly along with the headache, or by the headache, or may even be part of the triggering mechanisms for the headache. The visual system is complex in nature. Given the obvious pervasiveness of visual symptomatology post-mTBI, which includes visually-triggered headaches, it is reasonable to conclude that there are many common pathways shared by the dynamic responsibilities of the visual system such as vergences, accommodation, fixation disparity, saccades and pursuits and those pathways involved in headache. Further research is needed to not only identify those shared pathways but to determine whether their interactions after TBI stem from the maladaptive activation of existing neural substrates or the development of new neural connections during the recovery period. The elucidation of these interactions could lead to new methods for prevention, mitigation, treatment, and rehabilitation of vision-related-headache after TBI.

Conflict of interest

The authors declare that they have no conflict of interest.