Virtual reality as a method of cognitive training of processing speed, working memory, and sustained attention in persons with acquired brain injury: a protocol for a randomized controlled trial.

BACKGROUND: Acquired brain injury (ABI) often leads to persisting somatic, cognitive, and social impairments. Cognitive impairments of processing speed, sustained attention, and working memory are frequently reported and may negatively affect activities of daily living and quality of life. Rehabilitation efforts aiming to retrain these cognitive functions have often consisted of computerized training programs. However, few studies have demonstrated effects that transfer beyond the trained tasks. There is a growing optimism regarding the potential usefulness of virtual reality (VR) in cognitive rehabilitation. The research literature is sparse, and existing studies are characterized by considerable methodological weaknesses. There is also a lack of knowledge about the acceptance and tolerability of VR as an intervention method for people with ABI. The present study aims to investigate whether playing a commercially available VR game is effective in training cognitive functions after ABI and to explore if the possible effects transfer into everyday functioning. METHODS: One hundred participants (18-65 years), with a verified ABI, impairments of processing speed/attention, and/or working memory, and a minimum of 12 months post injury will be recruited. Participants with severe aphasia, apraxia, visual neglect, epilepsy, and severe mental illness will be excluded. Participants will be randomized into two parallel groups: (1) an intervention group playing a commercial VR game taxing processing speed, working memory, and sustained attention; (2) an active control group receiving psychoeducation regarding compensatory strategies, and general cognitive training tasks such as crossword puzzles or sudoku. The intervention period is 5 weeks. The VR group will be asked to train at home for 30 min 5 days per week. Each participant will be assessed at baseline with neuropsychological tests and questionnaires, after the end of the intervention (5 weeks), and 16 weeks after baseline. After the end of the intervention period, focus group interviews will be conducted with 10 of the participants in the intervention group, in order to investigate acceptance and tolerability of VR as a training method. DISCUSSION: This study will contribute to improve understanding of how VR is tolerated and experienced by the ABI population. If proven effective, the study can contribute to new rehabilitation methods that persons with ABI can utilize in a home setting, after the post-acute rehabilitation has ended.

Neurocognitive outcomes in moderately preterm born adolescents.

BACKGROUND: Early preterm (EP) born children are at risk of neurocognitive impairments persisting into adulthood. Less is known about moderately to late (MLP) preterm born children, especially after early childhood. The aim of this study was to assess neurocognitive functioning of MLP adolescents regarding intelligence, executive and attentional functioning, compared with EP and full-term (FT) adolescents. METHODS: This study was part of the Longitudinal Preterm Outcome Project (LOLLIPOP), a large community-based observational cohort study. In total 294 children (81 EP, 130 MLP, and 83 FT) were tested at age 14 to 16 years, regarding intelligence, speed of processing, attention, and executive functions. We used the Dutch version of the Wechsler Intelligence Scale for Children-Third Edition-Dutch Version (WISC-III-NL), the Test of Everyday Attention for Children, and the Behavioural Assessment of the Dysexecutive Syndrome for Children. We assessed differences between preterm-born groups with the FT group as a reference. RESULTS: Compared to the FT group, MLP adolescents scored significantly lower on two subtasks of the WISC-III-NL, i.e. Similarities and Symbol Search. EP adolescents performed significantly lower on all neuropsychological tests than their FT peers, except for the subtask Vocabulary. The MLP adolescents scored in between FT and EP adolescents on all tasks, except for three WISC-III-NL subtasks. CONCLUSIONS: Neurocognitive outcomes of MLP adolescents fell mostly in between outcomes of their EP and FT peers. MLPs generally performed on a low-average to average level, and appeared susceptible to a variety of moderate neurodevelopmental problems at adolescent age, which deserves attention in clinical practice.

The vanishing of the ACoA syndrome after aneurysmal subarachnoid haemorrhage: New era, different management, fewer problems?

Historically, a specific set of symptoms has been related to the rupture and repair of anterior communicating artery (ACoA) aneurysms. These consequences were defined as the 'ACoA syndrome' and included observations of severe memory loss, confabulation and personality or behavioural changes. These observations correspond to neuropsychological impairments in memory, executive functions and social cognition. However, in more recent studies, the existence of such a distinct syndrome has been called into question. We aimed to investigate the existence of the ACoA syndrome, by combining analysis of our own data with a systematic review of the literature. Memory, executive functions and social cognition of subarachnoid haemorrhage patients with ACoA aneurysms (N = 28) were compared to patients with aneurysms in other locations (N = 66). Results showed no significant differences. Subsequently, a systematic review of the existing literature on the ACoA syndrome was performed using Embase and PubMed until October 2022. Studies that investigated cognitive functions after rupture and repair of ACoA aneurysms were included. The search yielded 847 unique entries and after screening titles and abstracts, 648 records were excluded. 199 full-text articles were assessed for eligibility and 55 articles were included. Evidence was found for the ACoA syndrome in studies between 1960 and 2000, with impairments in memory and executive problems in the majority of studies. However, the majority of studies from 2000 did not demonstrate a distinct ACoA syndrome, although neuropsychological measurements improved. This coincides with the changes in the management of ACoA aneurysms over the past decades, such as the emergence of endovascular treatment and improvement of neurointensive care. Therefore, we hypothesize that the management techniques of ACoA aneurysms until around 2000, i.e. mainly conventional clipping, could be related to the presence of symptoms of the ACoA syndrome.

Mental versus physical fatigue after subarachnoid hemorrhage: differential associations with outcome.

BACKGROUND AND PURPOSE: Fatigue is a major consequence of subarachnoid hemorrhage (SAH), but the specific characteristics are unclear. Our objective was to investigate the nature of post-SAH fatigue (mental or physical) and to determine the relationship with functional outcome in the chronic stage. Also, the possible influence of mood disorders and acute SAH-related factors [SAH type and external cerebrospinal fluid (CSF) drainage] on the presence of fatigue was investigated. METHODS: Patients with an aneurysmal SAH (aSAH) or angiographically negative SAH (anSAH) were assessed 3-10 years post-SAH (N = 221). Questionnaires were used to investigate mental and physical fatigue and mood. Functional outcome was examined with the Glasgow Outcome Scale Extended. Between-group comparisons and binary logistic regression analysis were performed. RESULTS: Frequencies of mental and physical fatigue were 48.4% and 38.5%, respectively, with prevalence of mental fatigue being significantly higher. A two-way anova with SAH type and external CSF drainage as independent variables and mental fatigue as dependent variable showed a significant main effect of CSF drainage only (P < 0.001). Only mental fatigue explained a significant part of the variance in long-term functional outcome (model χ2 = 52.99, P < 0.001; Nagelkerke R² = 0.32). CONCLUSIONS: Mental fatigue after SAH is a serious burden to the patient and is associated with impaired long-term functional outcome. Distinguishing different aspects of fatigue is relevant as mental post-SAH fatigue might be a target for treatment aimed to improve long-term outcome.

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.

Cognitive decline after major oncological surgery in the elderly.

BACKGROUND: Elderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients. METHODS: A consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests. RESULTS: Of the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47-60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6-16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3-27). In patients with lower pre-operative Mini-Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18-57), and in patients undergoing major surgery it was 18% (95% CI: 10.6-26). Of the cognitive domains, executive function was the most vulnerable to decline. CONCLUSION: About half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation.

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.

Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus. METHODS: Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed. RESULTS: A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities. CONCLUSIONS: Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.

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.

Parkinson's patients' executive profile and goals they set for improvement: Why is cognitive rehabilitation not common practice?

Impairments in executive functions (EF) are the core cognitive impairment in patients with Parkinson's disease (PD). Surprisingly, cognitive rehabilitation is not routinely offered to patients with PD. However, in patients with acquired brain injury (ABI), cognitive rehabilitation, in particular strategic executive training, is common practice and has been shown to be effective. In this study, we determined whether PD patients have different needs and aims with regard to strategic executive training than ABI patients, and whether possible differences might be a reason for not offering this kind of cognitive rehabilitation programme to patients with PD. Patients' needs and aims were operationalised by individually set goals, which were classified into domains of EF and daily life. In addition, patients with PD and ABI were compared on their cognitive, in particular EF, profile. Overall, PD patients' goals and cognitive profile were similar to those of patients with ABI. Therefore, based on the findings of this study, there is no reason to assume that strategic executive training cannot be part of standard therapy in PD. However, when strategic executive training is applied in clinical practice, disease-specific characteristics need to be taken into account.

Insight in schizophrenia: associations with empathy.

Many people with schizophrenia (50-80%) demonstrate impaired insight, something which has been associated with a poorer outcome. Two types of empathy can be distinguished: affective empathy via shared emotions and cognitive empathy, also referred to as Theory of Mind (ToM). ToM can be subdivided into cognitive ToM (knowledge about beliefs of other people via perspective taking) and affective ToM (knowledge about other people's emotions via perspective taking). Recent studies show a relationship between Theory of Mind (ToM) and insight. However, the relationship between affective empathy and insight in schizophrenia was not examined previously. This was the aim of the present study. We expected that affective empathy would show a stronger relationship with insight than both cognitive and affective ToM. We assessed forty-six patients with a diagnosis of schizophrenia, and fifty-three healthy controls were assessed with a test battery consisting of tests of social cognition (a self-rating scale for affective empathy, a ToM task assessing both cognitive and affective ToM, and two tests of emotion perception), verbal memory, executive functioning, psychomotor speed, and intelligence. Insight was assessed with item G12 of the PANSS-interview. A regression equation showed that affective empathy made the strongest unique contribution to insight, followed closely by affective ToM. Together, they explained 45% of the variance in insight. None of the other independent variables made a unique contribution to the prediction of insight. Both affective ToM and affective empathy are associated with insight in schizophrenia. Being able to take empathize with other peoples feeling at both the affective and cognitive level may enhance insight in schizophrenia.

Rehabilitation of executive disorders after brain injury: are interventions effective?

In this paper, the effectiveness of interventions for executive disorders was reviewed. The objective was to evaluate the internal and external validity of intervention studies. A total of 46 papers, describing 54 studies, conducted in the last two decades meeting several preset inclusion criteria, was included in this review. The studies were categorized into three treatment approaches in order to enhance comparability. The overall results show that many interventions yield positive outcomes and seem to be effective in reducing executive problems in brain-injured subjects. However, several studies have only an explorative intent and are based on less sophisticated experimental designs. The verification of their results is generally more tenuous. The internal validity, or the set-up of experimental conditions necessary to draw valid conclusions about treatment effectiveness, including the choice of well-matched control groups, or the randomization of patients over treatment and control conditions, is not always strong. The same conclusion can be drawn for the external validity of a number of the intervention studies; often evidence of generalization to real-life situations, long-term follow-up, and transfer to non-trained situations, were (partially) lacking in the studies under review. The authors are aware that the design of proper randomized controlled trials for the investigation of the treatment effectiveness of executive disorders is cumbersome and time consuming. Nonetheless, the provisional results of several well-designed studies described in this review make the effort worthwhile.

Construct validity of concepts of attention in healthy controls and patients with CHI.

The present study aimed to examine the construct validity of three aspects of attention, namely focused, divided, and supervisory control of attention. Factor-analytic techniques were applied to scores of healthy subjects on a series of neuropsychological tests tapping these aspects of attention. The two components found did not match the hypothesized aspects and were labeled as Memory-driven Action and Stimulus-driven Reaction. The second question was whether the same components could be found in a group of patients with CHI. The pattern of attentional functions found in healthy subjects had changed qualitatively in patients with CHI. A possible explanation for this result in terms of a shift from automatic to controlled processing is discussed.

Executive functioning, attention and frontal lesions in patients with chronic CHI.

To study the presence and nature of dysexecutive problems after CHI, a series of unstructured tasks tapping executive functioning were selected. These were administered to a group of 51 participants with CHI in the chronic stage (i.e. several years post-injury) and to 45 healthy controls. In addition, well-known structured tests of attention and planning were administered. Of the executive tasks, only the Executive Route Finding task showed a significant difference between both groups. A multivariate analysis on the attention tests showed a significant difference between groups, indicating that patients in the chronic stage still process information slower than controls. Within the patient group, patients with and without frontal focal lesions were also compared on executive and attention tests. No differences were found with respect to the latter. However, patients with frontal lesions performed worse on a measure of the Executive Route Finding task. It is concluded that patients with CHI, especially when they have frontal damage, have to rely more heavily on externally provided cues, but this dysexecutive problem can only be demonstrated in tasks that resemble daily life tasks by providing very little structure.

Recovery versus retest effects in attention after closed head injury.

Recovery in 60 patients with a closed-head injury (CHI) in the first year posttrauma was assessed repeatedly with a series of attention tests. A matched group of healthy subjects was tested at the same intervals to allow us to control for practice effects. The results of a multilevel analysis for longitudinal data show retest effects in all but one of the tests. Patients performed more poorly on all tests, but their results on each test appeared to show recovery over time. The indicator of recovery was an improvement in test performance that was greater than the retest effect shown by the controls. On most tests, the performance of the more severely injured patients was initially worse, but showed more recovery over time. Test results differed with respect to changes over time, sensitivity to severity of injury, and subject specific characteristics like age and vocational level. Recovery rate was not related to age or vocational status. Despite their recovery, the patient group was still impaired 1 year posttrauma on all tests sensitive to mental slowness. Outcome after 1 year, scored on a modified Glasgow Outcome Scale, was predicted to a small extent by PTA duration and initial performance on the RT-Distraction task. Return to work 2 to 5 years posttrauma was predicted by initial performance and improvement over time on the Stroop Color Word Test.

Deficits of attention after closed-head injury: slowness only?

The performance of a group of 60 severely closed-head-injured patients in the subacute stage of recovery on a series of tests addressing focused, divided, and sustained attention, and supervisory attentional control was compared to the performance of a matched group of 60 healthy controls. Patients performed significantly worse on each test with time pressure (those addressing focused and divided attention), indicating basic slowness of information processing, and on the self-paced tasks for supervisory attentional control. No indication was found of a sustained attention deficit. In a subsequent analysis the influence of the demonstrated slowness of information processing and other possibly confounding cognitive factors was controlled for by means of covariance analyses. This resulted in a disappearance of group differences on tests for focused and divided attention. The only difference that remained concerned a test for supervisory attentional control.

Spared recognition capacity in elderly and closed-head-injury subjects with clinical memory deficits.

This study describes the performance of three groups of subjects on a pictorial forced-recognition task, the Hundred Pictures Test. The aim was to determine whether subjects with memory deficits (elderly and closed-head-injured subjects) would perform as well as healthy young subjects, both on immediate and very long-term recognition. The results indicate that memory for complex meaningful pictures is spared in subjects with an otherwise impaired memory, and that despite increasing forgetting rates with increasing retention intervals (up to 27 weeks), still no differences are found between performance of these subjects and healthy young controls. It will be discussed how this result might be interpreted.

[Planning ability of older and younger adults]. / Planningsvermogen van oudere en jongere volwassenen.

This investigation was aimed at the effects of ageing on planning. The investigation was carried out with young adults, middle-aged adults and elderly. Because of a suggested resemblance of problems described in elderly with impairments in patients with prefrontal cortical damage, and because the prefrontal cortex is important for planning, a test specifically sensitive to planning deficits in left prefrontal patients, the Tower of London test, was administered. On this test, the elderly solved significantly less problems in the allotted time than the two younger groups. However, the elderly did not show the same type of problem as that described in prefrontal patients. Such patients perform significantly worse on first attempts (problems correctly solved in one attempt). On this variable the elderly in our study equalled the younger adults in performance. However, they less often succeeded when the first attempt was not correct. To check whether this result could be explained simply by decreased mental and psychomotor speed and visuo-spatial function, regression functions between age and Tower score were computed, partialing out scores on tests of these more elementary abilities. A significant effect of age remained, which we tentatively interpret as an effect on planning ability.