Central nervous system microbleeds in the acute phase are associated with structural integrity by DTI one year after mild traumatic brain injury: A longitudinal study.

INTRODUCTION: Several imaging modalities are under investigation to unravel the pathophysiological mystery of delayed performance deficits in patients after mild traumatic brain injury (mTBI). Although both imaging and neuropsychological studies have been conducted, only few data on longitudinal correlations of diffusion tensor imaging (DTI), susceptibility weighted imaging (SWI) and extensive neuropsychological testing exist. METHODS: MRI with T1- and T2-weighted, SWI and DTI sequences at baseline and 12 months of 30 mTBI patients were compared with 20 healthy controls. Multiparametric assessment included neuropsychological testing of cognitive performance and post-concussion syndrome (PCS) at baseline, 3 and 12 months post-injury. Data analysis encompassed assessment of cerebral microbleeds (Mb) in SWI, tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) of DTI (VBM-DTI). Imaging markers were correlated with neuropsychological testing to evaluate sensitivity to cognitive performance and post-concussive symptoms. RESULTS: Patients with Mb in SWI in the acute phase showed worse performance in several cognitive tests at baseline and in the follow-ups during the chronic phase and higher symptom severity in the post concussion symptom scale (PCSS) at twelve months post-injury. In the acute phase there was no statistical difference in structural integrity as measured with DTI between mTBI patients and healthy controls. At twelve months post-injury, loss of structural integrity in mTBI patients was found in nearly all DTI indices compared to healthy controls. CONCLUSIONS: Presence of Mb detected by SWI was associated with worse cognitive outcome and persistent PCS in mTBI patients, while DTI did not prove to predict neuropsychological outcome in the acute phase.

Three versus seven days to return-to-work after mild traumatic brain injury: a randomized parallel-group trial with neuropsychological assessment.

Although most patients with a mild traumatic brain injury (mTBI) recover within days to weeks, some experience persistent physical, cognitive and emotional symptoms, often described as post-concussion syndrome (PCS). The optimal recovery time including return-to-work (RTW) after mTBI is unclear. In this single-centre parallel-group trial, patients assigned three days (3D-group) or seven days (7D-group) sick leave were compared with a comprehensive neuropsychological test battery including the Post-Concussion Symptom Scale (PCSS) within one week, after three and 12 months post-injury. The influence of the effective time until RTW on post-concussional symptoms and cognitive performance was analysed. The 3D-group rated significantly higher mean scores in some PCSS symptoms, tended to fulfil diagnosis criteria of PCS more often and showed better cognitive performance in several neuropsychological test scores than the 7D-group at all three time-points of follow-up. Overall, patients returned to work 11.35 d post-injury, thus distinctly above both recommended sick leaves. There was a trend for longer sick leave in patients randomized into the 3D-group. Further analyses revealed that the group with an absolute RTW within one week showed lower symptom severity in fatigue at 3 and 12 months, less PCS and faster performance in fine motor speed at 12 months than the group with an absolute RTW after one week. Our data underline the heterogeneity of mTBI and show that acute and sub-acute symptoms are not prognostic factors for neuropsychological outcome at one year. Later, ability to work seems to be prognostic for long-term occurrence of PCS.

Diagnostic approaches to predict persistent post-traumatic symptoms after mild traumatic brain injury - a literature review.

Mild traumatic brain injury (mTBI) is one of the most frequently diagnosed neurological disorders in emergency departments. Although there are established recommendations for the diagnosis and treatment in the acute stage, there is an on-going debate in which diagnostic methods and risk factors predict unfavourable long-term outcome after mTBI. This literature review addresses the question, which diagnostic approaches may best predict persistent post-traumatic symptoms (pPTS). A literature search for experimental studies from January 2000 to September 2014 evaluating the following diagnostic approaches (1) susceptibility weighted imaging (SWI), (2) diffusion tensor imaging (DTI), (3) magnetic resonance spectroscopy (MRS), (4) functional magnetic resonance imaging (fMRI), as predictive factors of pPTS or unfavourable cognitive outcome in adult populations with mTBI was performed. DTI has been proved to be a valuable tool to identify diffuse axonal injury (DAI) after mTBI. Additionally, some studies showed associations between DAI and unfavourable cognitive outcome. SWI has shown to be a highly sensitive imaging method to identify microbleeds. The presence and quantity of microbleeds in this imaging technique can further provide aetiological evidence for pPTS. MRS provides information about local neurons metabolism and preliminary data show that creatine-phosphocreatine levels measured after mTBI are predictive of cognitive outcome and emotional distress. The results of one study have shown fMRI as a useful tool to differentiate mTBI patients with pPTS from controls and mTBI patients without pPTS in a resting-state condition. From the evaluated diagnostic approaches to predict pPTS after mTBI, DTI, SWI, MRS, and fMRI seem to have adequate sensitivity and specificity as predictive diagnostic tools for pPTS. Large longitudinal clinical trials are warranted to validate the prognostic applicability and practicability in daily clinical practice.

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND: In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS: To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS: We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS: This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.

Characteristics of patients without neuropsychological deficits following aneurysmal subarachnoid haemorrhage.

BACKGROUND: Previous studies have shown that the incidence of neuropsychological deficits (NPD) after aneurysmal subarachnoid haemorrhage (aSAH) is high despite excellent outcome evaluated by traditional neurological grading scales. The aim of this study was to elucidate the clinical characteristics in patients presenting with aSAH who had a good clinical outcome without NPD. METHODS: Files of patients treated for aSAH between January 2009 and August 2012 at the neurovascular centres of the Kantonsspital St. Gallen (KSSG) and Kantonsspital Aarau (KSA), respectively, were reviewed. Neuropsychological outcome was assessed by an experienced, independent neuropsychologist. Patients were graded as regular, or as having minimal-, moderate-, or severe disability according to normative population data. RESULTS: A total of 92 patients (35 men and 57 women) with a mean age of 51.4 ± 11.6 years were analysed. Eight of 92 patients (8.7 %) had no NPD at follow-up. Patients without NPD were admitted with lower median WFNS (1.00 vs. 2.00; p = 0.011) and Fisher grades (2.00 vs. 3.00; p = 0.001). They were equally distributed between clipping and coiling (four patients each). No patient with regular neuropsychological outcome displayed chronic hydrocephalus (p = 0.019) or developed delayed cerebral ischaemia (DCI) during the hospital course (p = 0.100). Five patients were graded as modified Rankin Scale (mRS) 0 and three patients as mRS 1 at discharge. CONCLUSION: Patients without NPD after aSAH are likely to present with mild admission scores, develop neither chronic hydrocephalus nor DCI. In this series the aneurysm occlusion modality did not influence the cognitive outcome.

Delayed cerebral ischemia predicts neurocognitive impairment following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Prior studies have shown that the incidence of neuropsychological deficits (NPDs) after aneurysmal subarachnoid hemorrhage (aSAH) is high despite excellent outcome according to neurologic grading scales. Delayed cerebral ischemia (DCI) occurs in 30% of patients after aSAH and significantly contributes to the mortality and morbidity of aSAH. We tested the hypothesis that DCI is associated with neuropsychological outcome. METHODS: Files of patients treated between January 2009 and August 2012 at 2 neurovascular centers were reviewed. Neuropsychological outcome was assessed in a face-to-face-interview of 2-2.5 hours' duration and graded as no (regular), minimal, moderate, or severe deficit according to normative population data by an experienced, independent neuropsychologist. The test battery was applied with consideration of the patients' individual premorbid level of workload and social activities and accounted for the following cognitive domains: memory, attention, executive function, visual and spatial perception, language and calculation, and behavior. RESULTS: Of 226 patients treated at 2 centers, 187 were discharged alive. Full neuropsychological outcome assessment was available in 92 patients. DCI developed in 28 (30.4%) patients; 24 of these patients (85.7%) showed moderate to severe NPD. From a univariate perspective, patients with DCI were 6.38 times as likely to experience moderate to severe NPD after aSAH as patients without DCI (odds ratio [OR]; 95% confidence interval [CI], 1.98-20.50; P = 0.002), which remained statistically significant after correction for admission World Federation of Neurological Surgeons Grading System and Fisher scores, patient age, hydrocephalus, and further potential confounders (OR, 4.9; 95% CI, 1.26-19.58; P = 0.022). Of all factors analyzed, DCI was the strongest predictor of NPD in the multivariate analysis, followed by chronic hydrocephalus (OR, 4.85; 95% CI, 1.26-18.63; P = 0.022) and patient age ≥ 50 years (OR, 4.06; 95% CI, 1.39-11.92; P = 0.001). CONCLUSIONS: Patients with evidence of DCI during their hospital course have a 5-fold increased risk of experiencing moderate to severe NPD compared with patients who do not develop DCI after aSAH. Secondary events occurring during acute hospitalization (DCI, hydrocephalus) may be more important to the overall neuropsychological outcome than hemorrhage (Fisher) and clinical severity (World Federation of Neurological Surgeons Grading System) scores at admission.

Prospective memory across the lifespan: investigating the contribution of retrospective and prospective processes.

Prospective memory performance follows an inverted U-shaped function across the lifespan. Findings on the relative contribution of purely prospective memory and retrospective memory processes within prospective memory to this trajectory are scarce and inconclusive. We analyzed age-related differences in prospective memory performance across the lifespan in a cross-sectional design including six age groups (N = 99, 7-83 years) and investigated possible mechanisms by experimentally disentangling the relative contributions of retrospective memory and purely prospective memory processes. Results confirmed the inverted U-shaped function of prospective memory performance across the lifespan. A significant interaction between process type and age group was observed indicating differential relative contributions of retrospective memory and purely prospective memory processes on the development of prospective memory performance. Our results showed that mainly the pure prospective memory processes within prospective memory lead to lower prospective memory performance in young children and old adults. Moreover, the relative contributions of the retrospective memory and purely prospective memory processes are not uniform at both ends of the lifespan, i.e., in later adulthood the purely prospective memory processes seem to determine performance to an even greater extent than in childhood. Nevertheless, age effects were also observed in the retrospective component which thus contributed to the prospective memory performance differences between the age groups.

Current practice in neuropsychological outcome reporting after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Neuropsychological deficits (NPD) are common in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise acceptable prognosis for sustained quality of life. There are only a few studies reporting outcome after aSAH, which used a standardized neuropsychological test battery as a primary or secondary outcome measure. Aim of this study was to determine the current practice of reporting NPD following aSAH in clinical studies. METHODS: A MEDLINE analysis was performed using the search term "subarachnoid haemorrhage outcome". The latest 1,000 articles were screened. We recorded study design, number of patients, and the presence of neuropsychological outcome report. Additionally, the time of testing after aSAH, the neuropsychological tests administered, as well as the percentage of patients with NPD were analyzed. RESULTS: A total of 324 publications between 2009 and 2012 were selected for further review. Of those, 21 studies (6.5%) reported neuropsychological outcome, in 2,001 of 346,666 patients (0.6%). The assessment of NPD differed broadly using both subjective and objective cognitive evaluation, and a large variety of tests were used. CONCLUSION: Neuropsychological outcome is underreported, and there is great variety in assessment in currently published clinical articles on aSAH. Prospective randomized trials treating aSAH may benefit from implementing more comprehensive and standardized neuropsychological outcome measures. This approach might identify otherwise unnoticed treatment effects in future interventional studies of aSAH patients.