Disentangling the effects of age and mild traumatic brain injury on brain network connectivity: A resting state fMRI study.

INTRODUCTION: Cognitive complaints are common shortly after mild traumatic brain injury (mTBI) but may persist up to years. Age-related cognitive decline can worsen these symptoms. However, effects of age on mTBI sequelae have scarcely been investigated. METHODS: Fifty-four mTBI patients (median age: 35 years, range 19-64 years, 67% male) and twenty age- and sex-matched healthy controls were studied using resting state functional magnetic resonance imaging in the sub-acute phase. Independent component analysis was used to identify intrinsic connectivity networks (ICNs). A multivariate approach was adopted to evaluate the effects of age and group on the ICNs in terms of (static) functional network connectivity (FNC), intensities of spatial maps (SMs) and time-course spectral power (TC). RESULTS: We observed significant age-related changes for a) FNC: changes between 10 pairs of ICNs, mostly involving the default mode (DM) and/or the cognitive-control (CC) domains; b) SMs: intensity decrease in clusters across three domains and intensity increase in clusters across two domains, including the CC but not the DM and c) TC: spectral power decrease within the 0-0.15 Hz range and increase within the 0.20-0.25 Hz range for increasing age within networks located in frontal areas, including the anterior DM. Groups only differed for TC within the 0.065-0.10 Hz range in the cerebellar ICN and no age × group interaction effect was found. CONCLUSIONS: We showed robust effects of age on connectivity between and within ICNs that are associated with cognitive functioning. Differences between mTBI patients and controls were only found for activity in the cerebellar network, increasingly recognized to participate in cognition. Our results suggest that to allow for capturing the true effects related to mTBI and its effects on cognitive functioning, age should be included as a covariate in mTBI studies, in addition to age-matching groups.

From 'miserable minority' to the 'fortunate few': the other end of the mild traumatic brain injury spectrum.

OBJECTIVES: This study, as part of the UPFRONT-study, aimed to study the patients that report zero complaints early after injury, a group that we named the 'fortunate few'. We focused on their demographic, clinical and premorbid characteristics, and examined whether they would remain asymptomatic. Moreover, we investigated the influence of anxiety and depression (HADS), and determined outcome (GOS-E) and quality of life (WHOQOL-BREF) 1 year after injury. METHODS: Patients with MTBI (Glasgow Coma Scale score 13-15), without complaints 2 weeks after injury were included. Follow-up took place at 3, 6 and 12 months after injury. RESULTS: Of the entire UPFRONT-cohort (n = 1151), 10% (n = 119) reported zero complaints 2 weeks after injury. More than half of these patients (57%) developed complaints at a later stage (M = 2, p < .001). Patients with secondary complaints had higher anxiety (p = .004) and depression (p = .002) scores, leading to less favourable outcome (p = .014) and a lower quality of life (p = .006) 1 year after injury compared to patients that remained asymptomatic. CONCLUSION: One in 10 patients with mTBI report zero complaints early after injury. Although they seem fully recovered early after injury, a substantial part may develop secondary complaints leading to less favourable outcome and lower quality of life, warranting further research of this interesting group.

Clinical relevance of microhemorrhagic lesions in subacute mild traumatic brain injury.

Magnetic resonance imaging (MRI) is often performed in patients with persistent complaints after mild traumatic brain injury (mTBI). However, the clinical relevance of detected microhemorrhagic lesions is still unclear. In the current study, 54 patients with uncomplicated mTBI and 20 matched healthy controls were included. Post-traumatic complaints were measured at two weeks post-injury. Susceptibility weighted imaging and T2*-gradient echo imaging (at 3 Tesla) were performed at four weeks post-injury. Microhemorrhagic lesions (1-10 mm) were subdivided based on depth (superficial or deep) and anatomical location (frontal, temporoparietal and other regions). Twenty-eight per cent of patients with mTBI had ≥1 lesions compared to 0 % of the healthy controls. Lesions in patients with mTBI were predominantly located within the superficial frontal areas. Number, depth and anatomical location of lesions did not differ between patients with and without post-traumatic complaints. Within the group of patients with complaints, number of complaints was not correlated with number of lesions. In summary, microhemorrhages were found in one out of four patients with uncomplicated mTBI during follow-up at four weeks post-injury, but they were not related to early complaints.

Outpatient follow-up after mild traumatic brain injury: Results of the UPFRONT-study.

OBJECTIVE: To investigate outpatient follow-up after mild traumatic brain injury (mTBI) by various medical specialists, for both hospitalized and non-hospitalized patients, and to study guideline adherence regarding hospital admission. METHODS: Patients (n = 1151) with mTBI recruited from the emergency department received questionnaires 2 weeks (n = 879), 3 months (n = 780) and 6 months (n = 668) after injury comprising outpatient follow-up by various health care providers, and outcome defined by the Glasgow Outcome Scale Extended (GOS-E) after 6 months. RESULTS: Hospitalized patients (60%) were older (46.6 ± 19.9 vs. 40.6 ± 18.5 years), more severely injured (GCS <15, 50% vs. 13%) with more Computed Tomography (CT) abnormalities on admission (21% vs. 2%) compared to non-hospitalized patients (p < 0.01) . Almost half of the patients visited a neurologist at the outpatient clinic within six months (60% of the hospitalized and 25% of the non-hospitalized patients (χ2 = 67.10, p < 0.01)), and approximately ten per cent consulted a psychiatrist/psychologist. Outcome was unfavourable (GOS-E <7) in 34% of hospitalized and 21% of non-hospitalized patients (χ2 = 11.89, p < 0.01). CONCLUSION: Two-thirds of all mTBI patients consult one or more specialists within six months after injury, with 30% having an unfavourable outcome. A quarter of non-hospitalized patients was seen at the outpatient neurology clinic, underling the importance of regular follow-up of mTBI patients irrespective of hospital admittance.

Subacute posttraumatic complaints and psychological distress in trauma patients with or without mild traumatic brain injury.

OBJECTIVE: To identify the frequency, nature and profile of complaints for trauma patients with and without mild traumatic brain injury (mTBI), and to assess their relation to anxiety and depression. METHODS: A prospective cohort study in a level-one trauma centre was conducted. Mild traumatic brain injury patients and trauma controls were approached for participation. Two weeks after injury, The Head Injury Symptom Checklist (HISC) and the Hospital Anxiety and Depression Scale (HADS) were administered. RESULTS: Two-hundred seventy two patients with mTBI and 125 TC patients completed the questionnaires. Differences were demonstrated between the two trauma populations on frequency and nature of reported complaints. Ordinal common factor analysis on the mTBI scores yielded three factors: mental distress, physical discomfort, and sensory disbalance, which were all significantly correlated to anxiety and depression scores. Discriminant analyses identified a subset of complaints which could allocate almost 80% of patients to the correct group. CONCLUSIONS: Patients with mTBI showed a different pattern of complaints than orthopaedic control patients. A mental distress factor consisting of both somatic and cognitive complaints proved to be most discriminating and showed high correlations with anxiety and depression.