Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

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.

The feasibility of fNIRS as a diagnostic tool for pediatric TBI: A pilot study.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) enables assessment of prefrontal hemodynamic response. This study explored the feasibility of fNIRS in determining hemodynamic changes related to cognitive task performance in pediatric traumatic brain injury (TBI) in order to assess its potential as a diagnostic tool. METHODS: We measured changes in oxygenated hemoglobin [O2Hb] during a verbal fluency task (VFT), which activates frontal brain regions involved in working memory, in 15 TBI patients and 21 healthy controls using a 3-channel fNIRS system. Baseline and absolute changes in [O2Hb] during the VFT were compared to the rest condition to obtain effect-scores. Patients were tested in the acute phase and six weeks after injury. Task-related fNIRS responses were categorized into positive, negative, and no response. RESULTS: For patients and controls, a positive response was observed in 61% (n = 22), a negative response in 19% (n = 7), and no response in 19% (n = 7). Patients showed a mean [O2Hb] effect-score of 2.18 compared to 2.52 in the control group (p = 0.743) in the acute phase after injury. Follow-up effect-scores did not differ significantly (p = 0.721). Decreased task performance was associated with a higher effect-score in controls compared to decreased task performance with lower effect-score in the patient group. DISCUSSION: Our study shows that it is feasible to assess hemodynamic response with fNIRS in pediatric TBI patients. A trend of reduced prefrontal hemodynamic response in patients in the acute phase after injury was found suggesting impairment in cognitive performance that warrants further study.

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.

Discrepancy between the initial assessment of injury severity and post hoc determination of injury severity in patients with apparently mild traumatic brain injury: a retrospective multicenter cohort analysis.

PURPOSE: Traumatic brain injury (TBI) is a major cause of trauma-related visits to emergency departments (ED). Determination of monitoring requirements of patients with apparently mild TBI is challenging. Patients may turn out to be more severely injured than initially assumed, and failure to identify these patients constitutes a serious threat to patient safety. We, therefore, aimed to identify clinical risk factors for more severe injuries in patients with apparently mild TBI. METHODS: In a retrospective cohort analysis performed at two level I trauma centers, 808 patients aged ≥ 16 presenting to the ED with head trauma and a Glasgow Coma Scale (GCS) score 13-15 who received a head CT scan were studied. Discrepancies between the initial TBI severity as determined by GCS and severity as determined post hoc by the Head Abbreviated Injury Score were assessed. Multiple logistic regression was used to identify risk factors of such discrepancies. RESULTS: 104 (12.9%) patients were more severely injured than initially classified. A GCS < 15 at presentation (GCS 13: OR 6.2, [95% CI 3.8-9.9]; GCS 14: OR 2.7, [2.0-3.7]), an SpO2 < 90% (OR 5.4, [1.2-23.4]), loss of consciousness (OR 2.3, [1.5-3.5]), absence of equal and reactive pupils (OR 2.1, [1.6-2.7]), transport by ambulance (OR 2.0, [1.7-2.4]), and use of anticoagulant drugs (OR 1.2, [1.1-1.3]) were independent risk factors of more severe injury. CONCLUSIONS: Six risk factors of more severe injury in patients presenting with apparently mild TBI were identified. Patients with any of these factors should be thoroughly monitored for signs of neurologic deterioration.

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.

[Addendum to the Dutch guideline for minor head/brain injury]. / Addendum richtlijn licht traumatisch hoofd-hersenletsel.

- After introduction of the Dutch guideline for 'Care for patients with minor head/brain injury' (LTH guideline) in 2010, the number of CT scans has increased. Some of these scans were for patients with only trivial trauma and may not have been necessary.- In addition, since this guideline was implemented, there have been changes in the use of anticoagulants and platelet aggregation inhibitors. Non-vitamin-K-dependent oral anticoagulants (NOACs) and platelet aggregation inhibitors, or combinations of these, are prescribed more often.- These two factors have led the Netherlands Society of Neurology to initiate a request for modification of the LTH guideline for adults in two ways: (a) identification of minimal or trivial trauma for which no CT scan is required and (b) inclusion of NOACs and platelet aggregation inhibitors, or combinations of these, in the guideline.

The association between microhaemorrhages and post - traumatic functional outcome in the chronic phase after mild traumatic brain injury.

PURPOSE: In the chronic phase after mild traumatic brain injury (mTBI), microhaemorrhages are frequently detected on magnetic resonance imaging (MRI). It is however unclear whether microhaemorrhages are associated with functional outcome and which MRI sequence is most appropriate to address this association. We aimed to determine the association between microhaemorrhages and functional outcome in the chronic posttraumatic phase after injury with the most suitable MRI sequence to address this association. METHODS: One hundred twenty-seven patients classified with mTBI admitted to the outpatient clinic from 2008 to 2015 for persisting posttraumatic complaints were stratified according to the presence of MRI abnormalities (n = 63 (MRI+ group) and n = 64 without abnormalities (MRI- group)). For the detection of microhaemorrhages, susceptibility-weighted imaging (SWI) and T2* gradient recalled echo (T2*GRE) were used. The relation between the functional outcome (dichotomized Glasgow Outcome Scale Extended scores) and the number and localization of microhaemorrhages was analysed using binary logistic regression. RESULTS: SWI detected twice as many microhaemorrhages compared to T2*GRE: 341 vs. 179. Lesions were predominantly present in the frontal and temporal lobes. Unfavourable outcome was present in 67% of the MRI+ group with a significant association of total number of microhaemorrhages in the temporal cortical area on SWI (OR 0.43 (0.21-0.90) p = 0.02), with an explained variance of 44%. The number of microhaemorrhages was not correlated with the number of posttraumatic complaints. CONCLUSION: An unfavourable outcome in the chronic posttraumatic phase is associated with the presence and number of microhaemorrhages in the temporal cortical area. SWI is preferably used to detect these microhaemorrhages.

Influence of guidelines on management of paediatric mild traumatic brain injury: CT-assessment and admission policy.

BACKGROUND: The annual number of paediatric injury-related emergency visits and application of computed tomography (CT) has substantially increased, with associated higher risk of malignancies. In 2010, a guideline for CT-assessment based on risk factors for patients with mild traumatic brain injury (mTBI) became effective in all Emergency Departments (ED) in the Netherlands. This study evaluated the influence of this guideline on the frequency of CT-assessments, hospital admissions and factors that are related to guideline adherence. METHODS: Retrospective cohort study of paediatric mTBI (<18 years), defined by Glasgow Coma Scale score of 13-15 admitted to the ED of the University Medical Center Groningen from 2008 to 2014. Data before (pre-GL) and after (post-GL) introduction of the guideline were evaluated. Primary outcome parameters were frequency of CT-assessments and hospital admissions after ED. RESULTS: In total 633 patients were enrolled and data from pre-GL (n = 216) and post-GL (n = 315) were compared. Mean age was 7.9 years (SD 5.9), 59% were male. CT-assessments increased from 32% to 46% (p = .001), mostly in children aged 6-18 years. Hospital admissions increased from 38% to 54% (p < .001), mostly in children <6 years. No significant increase in CT-abnormalities is seen. Guideline adherence was 57%, although CT-assessments varied from 44 to 100% depending on presence of specific major risk factors. CONCLUSIONS: Introduction of a new guideline on management of paediatric mTBI showed significant increase in CT-assessments and more hospital admissions. In clinical practice, despite increase of guideline adherence the applications of cranial CT-scan varies within age groups and depends on the weighing of risk factors.

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.

[Identifying mild traumatic brain injury: clinical signs and consequences]. / Herkenning van licht traumatisch hersenletsel.

Identification of patients with mild traumatic brain injury (TBI) is important since 85,000 patients visit the emergency department with a head trauma annually. Although most patients recover well, 15-20% of the patients with head trauma develop persistent symptoms that interfere with resumption of daily activities. It is particularly important to identify the clinical signs that define mild TBI. Presence of anterograde amnesia after the injury, for example, is an important clinical diagnostic sign to establish the diagnosis of TBI. Posttraumatic emotional distress may increase posttraumatic symptoms. General practitioners should be aware of the problems in this patient group and identify patients with mild TBI who are at risk of developing persistent symptoms that limit participation in society.

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.

Resting functional imaging tools (MRS, SPECT, PET and PCT).

Functional imaging includes imaging techniques that provide information about the metabolic and hemodynamic status of the brain. Most commonly applied functional imaging techniques in patients with traumatic brain injury (TBI) include magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), positron emission tomography (PET) and perfusion CT (PCT). These imaging modalities are used to determine the extent of injury, to provide information for the prediction of outcome, and to assess evidence of cerebral ischemia. In TBI, secondary brain damage mainly comprises ischemia and is present in more than 80% of fatal cases with traumatic brain injury (Graham et al., 1989; Bouma et al., 1991; Coles et al., 2004). In particular, while SPECT measures cerebral perfusion and MRS determines metabolism, PET is able to assess both perfusion and cerebral metabolism. This chapter will describe the application of these techniques in traumatic brain injury separately for the major groups of severity comprising the mild and moderate to severe group. The application in TBI and potential difficulties of each technique is described. The use of imaging techniques in children will be separately outlined.

Physician-based emergency medical service deployment characteristics in severe traumatic brain injury: a Dutch multicenter study.

INTRODUCTION: Prehospital guidelines advise advanced life support in all patients with severe traumatic brain injury (TBI). In the Netherlands, it is recommended that prehospital advanced life support is particularly provided by a physician-based helicopter emergency medical service (P-HEMS) in addition to paramedic care (EMS). Previous studies have however shown that a substantial part of severe TBI patients is exclusively treated by an EMS team. In order to better understand this phenomenon, we evaluated P-HEMS deployment characteristics in severe TBI in a multicenter setting. METHODS: The database included patient demographics, prehospital and injury severity parameters and determinants of EMS or EMS/P-HEMS dispatch in 334 patients with severe TBI admitted to level 1 trauma centres in the Netherlands. RESULTS: P-HEMS was deployed in 62% of patients with severe TBI. Patients treated by the P-HEMS had a higher injury severity score (29 (20-38)) vs. (25 (16-30); P<0.001), more frequently required blood product transfusions (41% vs. 29%; P=0.03) and recurrently suffered from TBI with extracranial injuries (33% vs. 6%; P<0.001) than patients solely treated by an EMS. The prehospital endotracheal intubation rate was higher in the P-HEMS group in isolated TBI (93% vs. 19%; P<0.001) or TBI with extracranial injuries (96% vs. 43%; P<0.001) compared to the EMS group. In the EMS group, more patients were secondary referred to a level 1 trauma centre (32% vs. 4%; P<0.001 vs. P-HEMS). Despite higher injury severity levels in P-HEMS patients, 6-month mortality rates were similar among groups, irrespective of the presence of extracranial injuries in addition to TBI. Deployment of P-HEMS estimated 52% and 72% (P<0.001) in urban and rural regions, respectively, with comparable endotracheal intubation rates among regions. CONCLUSIONS: This study shows that a physician-based HEMS was more frequently deployed in patients with severe TBI in the presence of extracranial injuries, and in rural trauma regions. Treatment of severe TBI patients by a paramedic EMS only was associated with a higher incidence of secondary referrals to a level I trauma centre. Our data support adjustment of local prehospital guidelines for patients with severe TBI to the geographical context.

Effects of physician-based emergency medical service dispatch in severe traumatic brain injury on prehospital run time.

INTRODUCTION: Prehospital care by physician-based helicopter emergency medical services (P-HEMS) may prolong total prehospital run time. This has raised an issue of debate about the benefits of these services in traumatic brain injury (TBI). We therefore investigated the effects of P-HEMS dispatch on prehospital run time and outcome in severe TBI. METHODS: Prehospital run times of 497 patients with severe TBI who were solely treated by a paramedic EMS (n = 125) or an EMS/P-HEMS combination (n = 372) were retrospectively analyzed. Other study parameters included the injury severity score (ISS), Glasgow Coma Scale (GCS), prehospital endotracheal intubation and predicted and observed outcome rates. RESULTS: Patients who received P-HEMS care were younger and had higher ISS values than solely EMS-treated patients (10%; P = 0.04). The overall prehospital run time was 74 ± 54 min, with similar out-of-hospital times for EMS and P-HEMS treated patients. Prehospital endotracheal intubation was more frequently performed in the P-HEMS group (88%) than in the EMS group (35%; P<0.001). The prehospital run time for intubated patients was similar for P-HEMS (66 (51-80)min) and EMS-treated patients (59 (41-88 min). Unexpectedly, mortality probability scores and observed outcome scores were less favourable for EMS-treated patients when compared to patients treated by P-HEMS. CONCLUSION: P-HEMS dispatch does not increase prehospital run times in severe TBI, while it assures prehospital intubation of TBI patients by a well-trained physician. Our data however suggest that a subgroup of the most severely injured patients received prehospital care by an EMS, while international guidelines recommend advanced life support by a physician-based EMS in these cases.

GFAP and S100B in the acute phase of mild traumatic brain injury.

OBJECTIVE: The biomarkers glial fibrillary acid protein (GFAP) and S100B are increasingly used as prognostic tools in severe traumatic brain injury (TBI). Data for mild TBI are scarce. This study aims to analyze the predictive value of GFAP and S100B for outcome in mild TBI and the relation with imaging. METHODS: In 94 patients biomarkers were determined directly after admission. Collected data included injury severity, patient characteristics, admission CT, and MRI 3 months postinjury. Six months postinjury outcome was determined with Glasgow Outcome Scale Extended (GOSE) and return to work (RTW). RESULTS: Mean GFAP was 0.25 µg/L (SD 1.08) and S100B 0.54 µg/L (SD 1.18). In 63% GFAP was not discernible. GFAP was increased in patients with an abnormal CT (1.20 µg/L, SD 2.65) compared to normal CT (0.05 µg/L, SD 0.17, p < 0.05). Also in patients with axonal injury on MRI GFAP was higher (0.65 µg/L, SD 0.91 vs 0.07 µg/L, SD 0.2, p < 0.05). GFAP was increased in patients with incomplete RTW compared to complete RTW (0.69 µg/L, SD 2.11 vs 0.12 µg/L, SD 0.38, p < 0.05). S100B was not related to outcome or imaging studies. In multivariate analysis GFAP was not predictive for outcome determined by GOSE and RTW. CONCLUSIONS: A relation between GFAP with imaging studies and outcome (determined by RTW) was found in contrast to S100B. As the positive predictive value of GFAP is limited in this category of TBI patients, this biomarker is not suitable for prediction of individual patient outcome.

Traumatic cervical artery dissection in head injury: the value of follow-up brain imaging.

INTRODUCTION: Traumatic cervical artery dissection (TCAD) is a relative infrequent complication of traumatic brain injury (TBI). Since TCAD is associated with morbidity in a considerable percentage of patients, it is important to obtain clues for recognising TCAD in this category of patients. METHODS: Retrospective case-cohort study in severe TBI patients. RESULTS: Five patients with traumatic cervical artery dissection after severe TBI, leading to ischemic strokes, are described. Secondary deterioration to coma was present in four out of five patients during admission. The diagnosis of TCAD was delayed in most cases because the secondary deterioration was often attributed to multisystem problems related to trauma patients, i.e. shock or hypoxia or medication effects. Local clinical symptoms and signs suggestive of TCAD are difficult to detect in this patient group. In all patients, the CT-scan on admission demonstrated no abnormalities. A follow-up scan at day 2 revealed that in all patients abnormalities in the vascular territories had evolved. CONCLUSION: With this case-cohort study we underline the importance of considering TCAD in severe TBI patients and emphasise the role for standard follow-up brain imaging. Also possible treatment consequences are discussed.

Cortico-thalamic activation in generalized status epilepticus, a PET study.

In a patient with a refractory generalized convulsive status epilepticus, the ictal distribution of regional cerebral glucose was assessed with positron emission tomography (PET). Synchronized seizure activity in the EEG was associated with bilateral metabolic activation of medial sensorimotor regions, anterior cingulate cortex, striatum and thalamus. This pattern with focal cortical activation supports the concept that a cortical focus may drive epilepsy, while the thalamus mediates synchronization of neuronal activity as reflected in the EEG.

[Physical diagnosis--the Glasgow coma scale for the measurement of disturbances of consciousness]. / Fysische diagnostiek--de Glasgow-comaschaal voor het meten van bewustzijnsstoornissen.

The Glasgow coma scale (GCS) may be used for the evaluation of disturbances of consciousness. The GCS is a reliable and reproducible test that can easily be carried out at the patient's bedside. The GCS can be used to assess the severity of a head injury and to determine the prognosis of the patient. The prerequisites for a reliable determination of the GCS-score are training of inexperienced personnel, re-assessment by a physician with experience in neurology, correction for external factors and reporting in accordance with a protocol.