Introduction

Tics are characterized by repeated, non-rhythmic, and sudden movements (i.e., motor tics) and/or vocalizations (i.e., vocal or phonic tics) [1]. Tics vary in complexity, with simple motor and vocal tics lasting a short duration and appearing or sounding purposeless (e.g., eye darting or blinking, shoulder shrugs, head jerks, throat clearing, humming, grunting), while complex tics involve multiple sequential movements and/or vocalizations, causing them to appear or sound more elaborate, orchestrated, and purposeful (e.g., chains of facial and head movements, tapping, jumping, writing tics, words, phrases, echolalia, coprolalia) [2]. Motor tics typically develop in a rostral-caudal manner, with tics involving the face/head emerging initially, and tics involving the torso and outer extremities developing as time progresses [3]. Additionally, both motor and vocal tics tend to increase in complexity over time, with initial tics involving simple movements and/or vocalizations, and subsequent tics often involving multiple chained movements or sounds. Further, tics typically follow a waxing and waning course, with symptoms increasing and decreasing over days, weeks, months, and years either spontaneously or in line contextual changes [3]. With up to 20% of school-aged children experiencing tics for at least some period of time [4], they are a relatively common occurrence among youth. Indeed, the onset of tics typically occurs during early childhood between the ages of 5 and 7 years on average [5, 6], with adult onset of tics considered to be rare [7]. Although most tics dissipate within 6 months of their initial onset, for individuals presenting with tics lasting longer than a year, a tic disorder diagnosis may be warranted.

The etiology of tic disorders has been proposed to be influenced by multiple factors. Genetic associations [8], dysfunction within brain structures (basal ganglia) [9] and circuits (cortico-striatal-thalamo-cortical loop) [10], and excess postsynaptic expression of dopaminergic receptor D2 [11] have consistently been implicated in the development and maintenance of tic disorders. However, tic disorders appear to onset spontaneously, and temporally related biological triggers are relatively less understood. Nevertheless, tics may present secondary to a range of other neurological, chemical, psychological, or external factors, including TBI [12]. Across 155 clinic-referred tic patients treated in a movement disorders clinic, tics were reported to occur or significantly worsen following head trauma in 2.5% of patients [12].

Traumatic brain injury (TBI) is a growing health concern, with the CDC estimating that 2.5 million US individuals present to the emergency room with TBI each year [13•]. Falls, blows to the head, motor vehicle accidents, and sports-related injuries are the leading causes of TBI [13•, 14]. TBIs are classed by severity (i.e., mild, moderate, severe) established through presence and degree of loss of consciousness, altered cognition, memory loss, and brain damage [15, 16]. Moderate and severe TBI is more likely to involve penetration of the skull and brain tissue resulting in damage and requiring intensive care or surgical intervention [15]. In contrast, mild TBI or concussion refers to a non-penetrating head injury caused by direct external force to the head, neck, face, or other body region. Mild TBI may or may not result in loss of consciousness, but often leads to short-term impairment in physical, cognitive, and/or emotional functioning [17, 18•]. Headache and dizziness are the most frequently reported complaints [19], with memory impairment, nausea, fatigue, irritability, depression, emotional lability, insomnia, and noise intolerance also occurring [15, 20].

In select cases, patients may develop involuntary movements following TBI, with tremor, dystonia, chorea, parkinsonism, and/or tics presenting subsequent to severe TBI in 13 to 66% of cases [21, 22]. The link between tics and TBI has been described in a number of case reports [23]. However, there is a paucity of literature on this phenomenon. In order to inform our understanding of the pathophysiology of tics, consideration should be given to the clinical characteristics, brain morphology, and tic symptom recovery among patients presenting with tics following TBI.

Patient Characteristics

This paper presents a review of case reports (see Table 1) describing three youth and 22 adult patients ranging in age from 6 to 55 years at the time of their visits, and presenting with tic symptoms following varying degrees of TBI. Age of trauma onset was reported to be early childhood in 4/25 (16.0%) cases [26, 34, 39, 41], adolescence in 2/25 (8.0%) cases [24], and 18 years and above in 5/25 (20.0%) cases [30, 32, 36, 38]. For most remaining cases, age of trauma was not clearly stated but is presumed to be in adulthood based on chronological age of the patient at the time of the report. Seventeen of the 25 patients (68.0%) were male and seven of the 25 (28.0%) patients were female, with sex going unreported in two cases. Incidents leading to head trauma included motor vehicle accidents in the majority (20/25; 80.0%) of cases, followed by falls in 2/25 (8.0%) cases [34, 35], being struck by an object in 1/25 (4.0%) cases, and unspecified injuries in 2/25 (8.0%) cases [37].

Table 1 Summary of cases series and reports describing tics emerging subsequent to traumatic brain injury
Full size table

Post-traumatic Brain Injury Symptoms

Loss of consciousness following the concussion was reported in 12/25 patients (48.0%), with no loss of consciousness reported in 6/25 patients (24.0%). Physical and cognitive symptoms were reported across cases, and included memory problems [27, 29, 30, 38, 40•], poor impulse control [25, 30] and aggressive thoughts [24], reduced sensory perception [29, 30], poor balance [27, 30], hemiparesis or muscle weakness [26, 27], and impaired concentration [26, 27]. Further, at least one of the patients had a severe previous concussion, resulting in persistent short-term memory loss 2 years prior to the second one [30]. Emotional problems (i.e., depression, restricted affect, anxiety, irritability) were also noted [24, 29, 30, 38].

Tic Onset Latency and Topography

The latency between the head trauma and tic onset was reported in some cases. Tics presented within a few hours post-trauma in 1/25 (4.0%) case [32], 1 to about 4 days in 3/25 (12.0%) cases [29, 30], 2 to 3 weeks in 3/25 (12.0%) cases [29, 36], < 2 to 5 months in 6/25 (24%) cases [25, 30, 31, 38, 39, 41], and within about 1 year in 4/25 (16.0%) cases [26, 27, 29, 32]. On the higher end of the range, tics were reported to emerge a few years following the head trauma in one case [24] and 6 years in another [34]. In the majority of cases, patients presented with only simple motor tics, particularly involving the eyes, face, head, and neck. In some cases, simple motor tics evolved into more complex limb movements over time [34, 38, 41]. Simple and/or complex vocal tics were also present in several cases but were more likely to emerge after motor tics. Coprolalia and echolalia were present in each of five (out of 25) cases (20.0%) and often co-occurred. Further, the presence of obsessive-compulsive symptoms was reported post-concussion in 20% (5/25) of cases [24, 25, 30, 38].

Clinical History

In most cases (60.0%; 15/25), personal and family history were negative for both tics and/or related conditions (e.g., obsessive-compulsive symptoms, attention-deficit/hyperactivity disorder). However, 4/25 (16%) patients reported a family or personal history of tics. For example, a 15-year-old who had experienced a concussion at age 3, with tics emerging less than 2 months following the head trauma, and had two paternal uncles with facial tics [41]. A 33-year-old adult, who had presented with head and neck movements 2 weeks after hitting her head and shoulders during a fall, revealed she had engaged in repetitive chin movements since high school [35]. Another patient reported a possible prior sniffing tic [30]. In another case, severe worsening of pre-existing tic symptoms was observed following head trauma [37]. Finally, in a separate case, although the patient denied a family or personal history of tics, he reported childhood hyperactivity, distractibility and inattention, suggestive of attention-deficit/hyperactivity disorder (ADHD), and ongoing checking behavior, implying a history of obsessive-compulsive symptoms predating the trauma [31]. Personal and family history were not reported in the remaining 4/25 (16%) cases.

Laboratory Testing of Neural Structure and Functioning

Laboratory testing results describing neural structure and function were included in two-thirds of the case reports (16/25; 64%), with most tests including various forms of imaging (most commonly X-ray, computerized tomography (CT), magnetic resonance imaging (MRI)), and/or electroencephalography (EEG). Among these cases, testing results were unremarkable in 6/16 (37.5%) patients [29,30,31,32, 35, 36]. Among the remaining 10/16 (62.5%) patients, testing revealed several reports (5/16; 6.3%) of damage or dysfunction within the temporal region, with right temporal region fracture via x-ray [41], abnormal activity in the left temporal, frontotemporal, bitemporal and parietotemporal regions via EEG [26, 34, 40•, 41], and damage to the frontal and right temporoparietal white matter via MRI [30]. Decreased activation in the temporal region has been linked with increased tic severity [42]. Research suggests activation within the right temporoparietal junction in adults with TS is linked with premonitory urges to tic, repetition of others’ speech and movements, and impulse control deficits, and activation in the left temporoparietal junction was linked to increased socially inappropriate symptoms [43]. Further, cortical thinning in the temporal, frontal, and parietal regions is associated with increased tic severity [44].

Basal ganglia damage was reported in 3/16 (18.8%) cases, with hemorrhaging found across the basal ganglia [27], right basal ganglia [39], and left internal capsule [26]; tissue death noted in the left putamen, globus pallidus, head of the caudate, and internal capsule [26]; and lesions present in the right basal ganglia and right putamen [27]. Indeed, the basal ganglia has been most frequently implicated in TS, with studies showing reduced basal ganglia volumes in patients with TS [45••, 46]. Another brain region reported to be damaged across several cases (4/16; 25.0%) was the ventricular system, with reports suggesting enlargement of lateral ventricles [30, 35, 39], ventricular reflux [39], and hemorrhaging within the left lateral ventricle [26]. Findings are mixed with respect to ventricular abnormalities in individuals with TS. Research has shown no significant differences in ventricular size between youth and adults with TS and healthy controls [36, 47••]. However, an analysis of psychiatric outcomes in 6-year-old children of low birthweight showed neonatal ventricular enlargement increased odds for any psychiatric disorder, tic disorders, and ADHD [48]. Further, in monozygotic twins with discordant tic severity, the left lateral ventricle was reduced in the twin with greater symptom severity, which may have suggested organic differences or medication effects [49].

Treatment of Tics Subsequent to Traumatic Brain Injury

Treatments described in these case reports often involved combined medication regimens or a series of medication trials. Often, patients reported adverse side effects, most commonly sedation [30,31,32,33,34,35], resulting in their discontinuation or substitution for a more promising medication in several cases. With respect to final reported treatment outcomes, tics were reported to have significantly improved in 7/21 (33%) cases [25,26,27, 29, 30, 41]. Across these cases the only or final medication attempted varied greatly, with phenytoin (anticonvulsant) and diazepam (anxiolytic and sedative) with intermittent barbiturate administration [41], botulinum toxin [30], tetrabenazine [25, 29], and haloperidol [26] included. Tics were deemed to have improved somewhat in 5/21 (23.8%) cases [24, 28, 32, 35, 38], for example, decreasing, but occasionally re-emerging during stressful situations [32], waxing and waning but generally improving [35], or persisting but becoming suppressible in public settings [38]. Among these patients who experienced some improvement, medications used were antipsychotics (i.e., haloperidol, pimozide [35], clonazepam [32, 38], and botulinum toxin [28].

In four cases, no information on tic outcomes was provided [24, 37, 39]. In 3/21 (14.3%) cases, tics improved slightly over the course of treatment, but with no change in status by the final follow-up [30, 33, 34]. In several other cases (5/21; 4.8%), medications were ineffective or discontinued due to adverse side effects [28, 29, 31, 32, 36]. In one case, neither the patient nor family were concerned about the movements or interested in receiving treatment for them [30], highlighting that tic symptoms post-concussion may not be bothersome enough to warrant treatment for all patients. And finally, in one case involving a trial of levodopa (a dopamine agonist) to aid memory, tics emerged following administration of the medication and diminished 3 days after stopping the medication. A later re-trial of the medication confirmed that levodopa was the likely culprit [40•].

Validity of Mild Traumatic Brain Injury Symptoms Including Tics

Mild TBI or concussion typically resolves within 3 months, however, in individuals with symptoms that persist beyond this window, a diagnosis of post-concussion syndrome may be warranted [15]. However, some have called into question the validity of post-concussion syndrome. One study [50] compared the frequency of parent endorsement of child health complaints, including tics among 102 youth ages 4 to 15 years with a history of isolated mild TBI to 102 control youth with a history of mild peripheral bodily injury matched on age, sex, and date of trauma-related admission. This study was performed through a two-stage survey process to reduce expectancy bias. First, in the absence of any direct reference to the prior trauma, parents were mailed and asked to complete surveys regarding their child’s demographics, medical history, and presence and severity of health-related/physical symptoms. Second, upon receiving initial survey responses, parents were mailed an additional survey regarding history of mild TBI, which the researchers used to confirm the assignment of the survey responses to the head trauma group and exclude any cases in which additional head trauma occurred since the initial patient visit.

Findings revealed tics were endorsed at respective rates of 28.4% in parents of youth with concussion history and 31.4% in parents of youth with a history of peripheral bodily injury, with no significant group differences observed. Essentially, there were no significant differences between groups for all symptoms except for parental concerns regarding the possibility of brain damage, which parents of youth with a history of concussion endorsed at higher rates. The presence of headache, learning difficulty, and sleep disorder symptoms significantly predicted the increased likelihood of concern [50]. As there was no excess of tic symptom occurrence in the head trauma group, this suggests tics are not a common post-concussion symptom at least in children and younger adolescents. The authors also question the likelihood of physical symptoms being directly linked to concussion and suggest that they may be a product of psychological factors or stress related to the traumatic incident. In general, findings were concordant with a previous similarly designed study performed in adults, although no questions on tics were included in that study [51]. However, this study has some limitations. We lack information on the children’s health status prior to their head or peripheral body trauma. Further, parents were asked to rate general health status without regard for links with the trauma. This was important to reduce expectancy bias. However, as such, the degree to which physical symptoms can be attributed to the trauma is unclear. Additionally, the age range of the sample (i.e., 4 to 15) overlaps with the period of average age of tic onset (i.e., 5 to 7) [6]. Therefore, it is possible that tics may have emerged for these school-aged children even without head trauma.

Conclusion

The present review summarizes case reports and series describing tics emerging or worsening following TBI. With respect to demographics, patients described in the reports were predominantly male. This is in line with the higher preponderance of TS in males relative to females (with a ratio of 3:1) [52]. As such, the higher incidence of males among these cases is likely reflective of male sex being a risk factor for tic occurrence. Additionally, in several of the patients, there was a family history of tics or common co-occurring symptoms, which is in line with research demonstrating the heritability of TS. Further, mild tics were present or suspected prior to the head trauma in three cases; and a history of obsessive-compulsive disorder (OCD) and ADHD symptoms was present in a separate patient. This raises the question as to whether additional patients may have had a personal history of tics prior to TBI that went undetected. Age of head trauma onset was reported or presumed to be in adulthood in most cases. However, in four of 25 cases (16.0%), it was reported to be in early childhood (i.e., ages 3, 5, and < 6 years, < 7.5 years). This raises challenges related to the attribution of tics to TBI. Since tics typically onset during early childhood, it cannot be determined whether tics would have emerged naturally in these children even without a history of TBI. Relatedly, the study evaluating the validity of physical complaints presenting following mild TBI showed no significant differences in parent-report of tics in youth between those with head trauma history versus peripheral injury history [50]. This suggests that tics emerging post-TBI are relatively uncommon in youth. Further, latency between head trauma and age of onset varied widely across cases. Whether this variation holds clinical significance (e.g., links between latency and trauma severity or affected brain region) cannot be ascertained from these few case reports.

With respect to tic topography, presentation of motor tics involving the face, head, and neck was common, with motor tics increasing in complexity to involve the extremities over time in several other cases. Vocal tics were also common but often developed following motor tics. This pattern of tic emergence mirrors the rostral to caudal and motor to vocal development of tics in TS [3]. Obsessive-compulsive symptoms emerged post-TBI in 20% of cases. Obsessive-compulsive disorder and TS commonly co-occur, overlap with respect to patterns of brain dysfunction, and have symptoms (e.g., complex tics and compulsions) that are difficult to discern at times [53]. The presence of obsessive-compulsive symptoms presenting post-trauma in these cases is also in line with the common co-occurrence between TS and OCD.

Among patients who had undergone neuroimaging, findings most often revealed damage to the basal ganglia, ventricular system, and temporal region, with damage sometimes present across multiple regions within the same patient. Neural abnormalities noted in these reports are consistent with extant knowledge regarding neural sequelae within TS and other persistent tic disorders However, given the lack of pre-TBI data, it is difficult to know if abnormal imaging findings were pre-existing. Nevertheless, broadly speaking, case report findings suggest there may be broad heterogeneity in neural dysfunction implicated in tic expression.

With respect to treatment outcome, tics appeared to improve significantly in seven cases and somewhat in five cases, with various medications trialed. However, the degree to which tics may have remitted without pharmacological intervention is unclear. More longitudinal follow-up and repeat neuroimaging of these patients are needed to address this important question.

Although informative, these case reports and series provide limited information for several reasons. First, the inconsistency across cases in reporting of patient demographics, clinical features, neuroimaging results, and timing of follow-up visits poses a challenge for identifying clinical patterns across similar cases. Second, causative links between TBI and tics cannot be determined and are more questionable in certain cases (e.g., tic onset observed 6-years post-head trauma in a child [34], and tic onset emerging following levodopa administration post-head trauma in an adult [41]). Further, with respect to pharmacological intervention, the open trial administration used in most cases limits the ability to discern the relative effectiveness of these medications on tic symptoms. Further, objective measurement of tics was lacking, with only one case report [25] including clinician-rated tic interview and video assessment of tics. In the future, patient assessments should be performed more thoroughly and systematically. Details regarding age of onset, clinical history, and neuroimaging results and treatment outcome should be included more consistently to allow for drawing of inferences across cases. There should also be greater use of standardized and validated measures of tic symptoms including the Yale Global Tic Severity Scale, a clinician-rated interview, subjective measures, and video-based observation of tics (See Cohen et al., 2013 for a review of tic assessment) [54]. Further, as utilized in two cases, single case designs [55] should be incorporated to more systematically test medication effects.

Ultimately, given the limited systematic study of the link between TBI and tics and the aforementioned methodological issues in the extant literature, there is presently no definitive evidence to support that brain trauma is causative for tics. Given these findings, should tics emerge around the same time as a TBI, typical treatments for tics should be pursued first (as needed). This remains an area ripe for examination, and this important line of research should be carried out in larger scale, systematic investigations that employ more rigorous methodology.