An update on tests used for intraoperative monitoring of cognition during awake craniotomy.

PURPOSE: Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A systematic review from 2018 about neuropsychological tests used during awake craniotomy made clear that until 2017 language was most often monitored and that the other cognitive domains were underexposed (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). The field of awake craniotomy and cognitive monitoring is however developing rapidly. The aim of the current review is therefore, to investigate whether there is a change in the field towards incorporation of new tests and more complete mapping of (higher-order) cognitive functions. METHODS: We replicated the systematic search of the study from 2018 in PubMed and Embase from February 2017 to November 2023, yielding 5130 potentially relevant articles. We used the artificial machine learning tool ASReview for screening and included 272 papers that gave a detailed description of the neuropsychological tests used during awake craniotomy. RESULTS: Comparable to the previous study of 2018, the majority of studies (90.4%) reported tests for assessing language functions (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). Nevertheless, an increasing number of studies now also describe tests for monitoring visuospatial functions, social cognition, and executive functions. CONCLUSIONS: Language remains the most extensively tested cognitive domain. However, a broader range of tests are now implemented during awake craniotomy and there are (new developed) tests which received more attention. The rapid development in the field is reflected in the included studies in this review. Nevertheless, for some cognitive domains (e.g., executive functions and memory), there is still a need for developing tests that can be used during awake surgery.

CT-optimal touch and chronic pain experience in Parkinson's Disease; An intervention study.

One of the most underdiagnosed and undertreated non-motor symptoms of Parkinson's Disease is chronic pain. This is generally treated with analgesics which is not always effective and can cause several side-effects. Therefore, new ways to reduce chronic pain are needed. Several experimental studies show that CT-optimal touch can reduce acute pain. However, little is known about the effect of CT-optimal touch on chronic pain. The aim of the current study is to investigate whether CT-optimal touch can reduce the chronic pain experience in Parkinson patients. In this intervention study, 17 Parkinson patients underwent three conditions; no touch, CT-optimal touch and CT non-optimal touch with a duration of one week each. During each touch week, participants received touch from their partners twice a day for 15 minutes. Results show that both types of touch ameliorate the chronic pain experience. Furthermore, it appears that it is slightly more beneficial to apply CT-optimal touch also because it is perceived as more pleasant. Therefore, we argue that CT-optimal touch might be used when immediate pain relief is needed. Importantly, this study shows that CT-optimal touch can reduce chronic pain in Parkinson's Disease and can be administered by a partner which makes it feasible to implement CT-optimal touch as daily routine.

Spatial factors influencing the pain-ameliorating effect of CT-optimal touch: a comparative study for modulating temporal summation of second pain.

Recent studies show that CT-optimal touch, gentle slow stroking of the skin, can reduce pain. However, much is unknown regarding the factors influencing its pain-ameliorating effect, such as tactile attention and touch application site. The current study investigates in 36 healthy individuals, whether CT-optimal touch can reduce temporal summation of second pain (TSSP) compared to CT non-optimal touch and tapping the skin. TSSP refers to activation of the C-nociceptors; by stimulating these fibers a burning and/or tingling sensation can be elicited. All participants underwent three conditions on both the contralateral and ipsilateral side of pain induction. The results show that tapping the skin did not reduce TSSP, meaning that pain reduction through touch cannot be explained by tactile attention effects. CT non-optimal touch only reduced TSSP when applied on the ipsilateral side. Importantly, CT-optimal touch effectively reduced TSSP when applied on the contralateral or ipsilateral side. Furthermore, CT-optimal touch was more effective in reducing TSSP compared to CT non-optimal touch and Tapping. This study shows that that CT-optimal touch can reduce TSSP and this effect appears to be independent of touch application site, which is highly relevant for implementing CT-optimal touch as a treatment.

Preserving the ability to discriminate between left and right; A case study.

Left-right orientation, a function related to the parietal lobe, is important for many daily activities. Here, we describe a left-handed patient with a right parietal brain tumour. During awake surgery, electric stimulation of the right inferior parietal lobe resulted in mistakes in his left-right orientation. Postoperatively our patient had no problems in discriminating left right. This case report shows that monitoring of left-right orientation during awake brain tumour surgery is feasible so that this function can be preserved.

Chronic pain relief after receiving affective touch: A single case report.

Affective touch is gentle slow stroking of the skin, which can reduce experimentally induced pain. Our participant, suffering from Parkinson's Disease and chronic pain, received 1 week of non-affective touch and 1 week of affective touch as part of a larger study. Interestingly, after 2 days of receiving affective touch, the participant started to feel less pain. After 7 days, the burning painful sensations fully disappeared. This suggest that affective touch may reduce chronic pain in clinical populations.

Complications, compliance, and undertreatment do not explain the relationship between cognition and survival in diffuse glioma patients.

Background: Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the relationship between cognition and survival was mediated by three different factors: undertreatment, complications of treatment, and compliance. We hypothesized that patients with cognitive impairment may undergo less intensive treatment, be less compliant, and suffer more from complications, resulting in shortened survival for cognitively impaired patients. Methods: In a retrospective cohort study of patients undergoing awake craniotomy between operative neuropsychological assessments in five cognitive domains. We used Structural Equation Modeling to perform mediation analyses. Mediation analyses are analyses to evaluate whether a variable is a factor in the causal chain, referred to as an intermediate factor. Results: In total 254 patients were included, of whom 111 patients were LGG patients and 143 were HGG patients. The most frequently impaired domain was memory (37.8% ≤-2 SD) in HGG and attention and executive functioning in LGG (33.3≤-1.5 SD). We confirmed the significant association between different cognitive domains and survival. These associations could not be explained by one of the aforementioned intermediate factors. Conclusions: This suggests that other mechanisms should be involved in the relation between cognition and survival. Hypothetically, cognitive functioning can act as a marker for diffuse infiltration of the tumor or cognitive functioning and survival could be determined by overlapping germline and somatic tumoral molecular-genetic factors.

Neural basis of affective touch and pain: A novel model suggests possible targets for pain amelioration.

Pain is one of the most common health problems and has a severe impact on quality of life. Yet, a suitable and efficient treatment is still not available for all patient populations suffering from pain. Interestingly, recent research shows that low threshold mechanosensory C-tactile (CT) fibres have a modulatory influence on pain. CT-fibres are activated by slow gentle stroking of the hairy skin, providing a pleasant sensation. Consequently, slow gentle stroking is known as affective touch. Currently, a clear overview of the way affective touch modulates pain, at a neural level, is missing. This review aims to present such an overview. To explain the interaction between affective touch and pain, first the neural basis of the affective touch system and the neural processing of pain will be described. To clarify these systems, a schematic illustration will be provided in every section. Hereafter, a novel model of interactions between affective touch and pain systems will be introduced. Finally, since affective touch might be suitable as a new treatment for chronic pain, possible clinical implications will be discussed.

Added Value of Cognition in the Prediction of Survival in Low and High Grade Glioma.

Background: Diffuse gliomas, which are at WHO grade II-IV, are progressive primary brain tumors with great variability in prognosis. Our aim was to investigate whether pre-operative cognitive functioning is of added value in survival prediction in these patients. Methods: In a retrospective cohort study of patients undergoing awake craniotomy between 2010 and 2019 we performed pre-operative neuropsychological assessments in five cognitive domains. Their added prognostic value on top of known prognostic factors was assessed in two patient groups [low- (LGG) and high-grade gliomas (HGG]). We compared Cox proportional hazards regression models with and without the cognitive domain by means of loglikelihood ratios tests (LRT), discriminative performance measures (by AUC), and risk classification [by Integrated Discrimination Index (IDI)]. Results: We included 109 LGG and 145 HGG patients with a median survival time of 1,490 and 511 days, respectively. The domain memory had a significant added prognostic value in HGG as indicated by an LRT (p-value = 0.018). The cumulative AUC for HGG with memory included was.78 (SD = 0.017) and without cognition 0.77 (SD = 0.018), IDI was 0.043 (0.000-0.102). In LGG none of the cognitive domains added prognostic value. Conclusions: Our findings indicated that memory deficits, which were revealed with the neuropsychological examination, were of additional prognostic value in HGG to other well-known predictors of survival.

Cognitive impairments are independently associated with shorter survival in diffuse glioma patients.

BACKGROUND: Diffuse gliomas (WHO grade II-IV) are progressive primary brain tumors with great variability in prognosis. Cognitive deficits are of important prognostic value for survival in diffuse gliomas. Until now, few studies focused on domain-specific neuropsychological assessment and rather used MMSE as a measure for cognitive functioning. Additionally, these studies did not take WHO 2016 diagnosis into account. We performed a retrospective cohort study with the aim to investigate the independent relationship between cognitive functioning and survival in treatment-naive patients undergoing awake surgery for a diffuse glioma. METHODS: In patients undergoing awake craniotomy between 2010 and 2017, we performed pre-operative neuropsychological assessments in five cognitive domains, with special attention for the domains executive functioning and memory. We evaluated the independent relation between these domains and survival, in a Cox proportional hazards model that included state-of-the-art integrated histomolecular ('layered' or WHO-2016) classification of the gliomas and other known prognostic factors. RESULTS: We included 197 patients. Cognitive impairments (Z-values ≦ - 2.0) were most frequent in the domains memory (18.3%) and executive functioning (25.9%). Impairments in executive functioning and memory were significantly correlated with survival, even after correcting for the possible confounders. Analyses with the domains language, psychomotor speed, and visuospatial functioning yielded no significant results. Extensive domain-specific neuropsychological assessment was more strongly correlated to survival than MMSE. CONCLUSION: Cognitive functioning is independently related to survival in diffuse glioma patients. Possible mechanisms underlying this relationship include the notion of cognitive functioning as a marker for diffuse infiltration of the tumor and the option that cognitive functioning and survival are determined by overlapping genetic pathways and biomarkers.

Neurocognitive changes after awake surgery in glioma patients: a retrospective cohort study.

PURPOSE: Deficits in neurocognitive functioning (NCF) frequently occur in glioma patients. Both treatment and the tumor itself contribute to these deficits. In order to minimize the harmful effects of surgery, an increasing number of patients undergo awake craniotomy. To investigate whether we can indeed preserve cognitive functioning after state-of-the art awake surgery and to identify factors determining postoperative NCF, we performed a retrospective cohort study. METHODS: In diffuse glioma (WHO grade 2-4) patients undergoing awake craniotomy, we studied neurocognitive functioning both pre-operatively and 3-6 months postoperatively. Evaluation covered five neurocognitive domains. We performed analysis of data on group and individual level and evaluated the value of patient-, tumor- and treatment-related factors for predicting change in NCF, using linear and logistic regression analysis. RESULTS: We included 168 consecutive patients. Mean NCF-scores of psychomotor speed and visuospatial functioning significantly deteriorated after surgery. The percentage of serious neurocognitive impairments (- 2 standard deviations) increased significantly for psychomotor speed only. Tumor involvement in the left thalamus predicted a postoperative decline in NCF for the domains overall-NCF, executive functioning and psychomotor speed. An IDH-wildtype status predicted decline for overall-NCF and executive functioning. CONCLUSIONS: In all cognitive domains, except for psychomotor speed, cognitive functioning can be preserved after awake surgery. The domain of psychomotor speed seems to be most vulnerable to the effects of surgery and early postoperative therapies. Cognitive performance after glioma surgery is associated with a combination of structural and biomolecular effects from the tumor, including IDH-status and left thalamic involvement.

Monitoring cognition during awake brain surgery in adults: A systematic review.

INTRODUCTION: Historically, most studies about awake brain surgery have focused on language or motor functions. More recently, other cognitive functions have also been assessed. However, a clear overview of the neuropsychological tests or test paradigms that are used during such procedures is missing. The primary research question of this review is: What neuropsychological tests or paradigms are used during awake brain surgery? This review aims to give an extensive overview about the assessment of cognition during awake brain surgery. METHOD: A systematic search was performed in PubMed and Embase. Studies about awake surgery that mentioned a specific test or test paradigm for assessing cognition were included in this review. RESULTS: The search yielded 4,052 articles. A manual selection for cognition in title and abstract resulted in 360 studies. Those were evaluated in full text; 212 articles described a cognitive task or paradigm. Further reference-list search yielded 20 more studies. In 207 of 232 studies, a test for assessment of language is reported. Tests for the visuospatial domain and motor and sensory functions are described in, respectively, only 23 and 20 studies. Tests for memory, calculation, emotions, or other cognitive functions are reported only in a minority of the included studies. CONCLUSIONS: Tests for assessment of language functions during awake brain surgery are widely reported. Other cognitive functions are underexposed. There is a need for development of tests or paradigms for assessment of other cognitive functions so that the broad spectrum of cognition can be monitored during awake brain surgery.

Anxiety in the preoperative phase of awake brain tumor surgery.

OBJECTIVE: Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we analyzed the prevalence and potential clinical predictors of anxiety in the pre-operative phase of an awake brain tumor surgery. PATIENTS AND METHODS: Seventy consecutive candidates for an awake brain tumor surgery were included. All patients received a neuropsychological pre-operative work-up. The Hospital Anxiety and Depression Scale (HADS) was administrated to investigate symptoms of anxiety. Demographic and medical data were extracted from patients' charts. Linear regression analyses, multiple regression analyses, t-tests for parametric and Mann-Whitney U tests for non-parametric data were used to analyze the relation between demographic and medical variables and pre-operative anxiety. RESULTS: Mean score on the anxiety scale of the HADS was 6.1 (SD=4.2, range 1-19) and 25% of the patients scored on or above the cut-off for anxiety symptoms (score >7). Women reported higher levels of anxiety than men (p<0.01). Furthermore, younger patient were more anxious than older patients (p<0.05). No other variables were significantly related to pre-operative anxiety. CONCLUSIONS: Merely, one in every four patients reported significant anxiety symptoms in the pre-operative phase. Besides gender and age, none of the other demographic or medical factors were significantly associated with the level of anxiety.

Cognitive disorders after sporadic ecstasy use? A case report.

Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is a 39-year-old man who used an ecstasy tablet in 2005. This resulted in severe confusion for a few days. The confusion was followed by persistent memory complaints and difficulties orientating in new surroundings. An extensive neuropsychological examination 7 years after the ecstasy use revealed a severe memory disorder. Furthermore, his performance on a virtual reality test of navigation showed serious problems navigating in new surroundings. In comparison with matched control subjects (Bayesian approach for single case studies) his scores were significantly impaired on several subtasks of the navigation test. On a magnetic resonance imaging (MRI) scan of the brain bilateral hippocampal atrophy and sclerosis were visible, comparable to previous MRI studies describing hippocampal damage following ecstasy ingestion. This case report describes persistent memory and navigation disorders after sporadic ecstasy use, supported by structural brain abnormalities seen on the MRI scan. These findings revive the debate on whether sporadic ecstasy use can cause persistent cognitive deficits.

Symptom Checklist 90-Revised in neurological outpatients.

The Symptom Checklist 90-Revised (SCL-90-R) is an international, widely used, self-report questionnaire of multidimensional complaints with normative data for healthy control subjects and psychiatric patients. The questionnaire is also often used in neurological patients. Little is known about the amount and pattern of complaints in this group, and normative data are lacking. We therefore analyzed self-reported symptoms on the SCL-90-R of a neurological population (N = 600). Moreover, we compared the answer patterns of five subgroups: neurodegenerative disease, cerebrovascular disease, epilepsy, brain tumor, and traumatic brain injury. Neurological outpatients scored significantly higher in comparison with normative data from healthy control subjects, with most pronounced scores on Inadequacy of Thinking and Acting, Depression, and Somatization (p < .01, effect sizes 1.69, 0.83, and 0.83). No differences between the various pathologies were found. Although it is difficult to determine whether the complaints arise directly from the neurological disease or more indirectly from psychiatric disturbances accompanying the disease, simply comparing a neurological patient to normative data for healthy control subjects can lead to inappropriate classifications. Complaints of our patients should not be directly interpreted as psychopathology. A two-step procedure in which scores on the SCL-90-R are first compared to healthy control subjects and secondly to neurological patients can be helpful in the interpretation.

Exploration of the Raven APM-National Adult Reading Test discrepancy as a measure of intellectual decline in older persons.

Previous studies have shown that the discrepancy between performance on "fluid" and "crystallized" intelligence measures may serve as an indicator for intellectual decline. The validity of this procedure in older persons is unknown. The present study developed a multiple regression equation, to predict the Raven Advanced Progressive Matrices (APM) score from the National Adult Reading Test (NART) score and demographic variables in a large sample of healthy older persons (n = 270). The discrepancy between the predicted and observed Raven APM scores was transformed into a percentile distribution as an indicator of intellectual decline, which can be used in clinical practice. The validity of the procedure was further examined by comparing the proportion of persons with a significant decline (at the -1 and -1.65 SD level) between two older patient samples (87 patients with cerebral stroke and 387 patients with diabetes mellitus) by means of χ(2) tests. There was a significantly higher rate of intellectual decline at the -1 SD ("below average") and -1.65 SD ("impaired") cutoff levels for patients with stroke compared with patients with diabetes (stroke, 34% and 14%; diabetes, 16% and 5%, p < .05). These findings suggest that the Raven APM-NART discrepancy may be a useful measure of intellectual decline in older persons.

Mild depressive symptoms do not influence cognitive functioning in patients with type 2 diabetes.

Type 2 diabetes (T2DM) is associated both with cognitive decrements and depressive symptoms. Since depression in itself has been associated with cognitive decrements we aimed to investigate the influence of depressive symptoms on the relation between T2DM and cognitive functioning. Data were derived from three independent studies on cognitive functioning in patients with T2DM (n=366) and controls without diabetes (n=204), two with longitudinal and one with only cross-sectional assessments. Depressive symptoms were measured with self-report inventories (CES-D or BDI-II). The composite z-score of the domains memory, information-processing speed, and attention and executive function was the primary cognitive outcome measure. Mixed linear regression analyses were used in a stepped approach to compare cognitive functioning between (1) patients with T2DM and controls (cross-sectionally and longitudinally), (2) participants with and without depressive symptoms, separately for patients and controls, and (3) patients and controls after adjustment for depressive symptoms. In addition the mediating effect of depressive symptoms was assessed with a bootstrapping technique. Depressive symptoms were present in 11% of the patients with T2DM and in 7% of controls (p=0.15). Cognitive performance in patients with T2DM was worse than in controls (overall difference composite z-score -0.13). However, T2DM was not associated with accelerated cognitive decline over three years of follow-up relative to controls. Controls with depressive symptoms performed worse than those without depressive symptoms, although not statistically significant. Performance in patients with T2DM with and without depressive symptoms was similar. Adjustment for depressive symptoms and estimation of the mediating effect showed that the difference between patients and controls was not mediated by depressive symptoms. In conclusion, the modest cognitive decrements that are associated with T2DM are not due to the presence of mild depressive symptoms.

The Telephone Interview for Cognitive Status (Modified): relation with a comprehensive neuropsychological assessment.

The modified Telephone Interview for Cognitive Status (TICS-m) is a widely used screening instrument for (Alzheimer's) dementia. Psychometric evaluation of the TICS-m is limited. This study examined the relation between the TICS-m and a comprehensive neuropsychological assessment in older persons (n = 243) without cognitive deficits. The TICS-m total score correlated with multiple cognitive domains (range r = .22-.49). Factor analysis of the TICS-m items yielded four interpretable factors: "verbal memory," "orientation/mental tracking," "language/reasoning," and "attention/working memory," which also showed (modest) correlations with the neuropsychological assessment (r = .02-.48). The TICS-m appears to reflect a "general cognitive ability" rather than, for example, memory functioning alone.

Intensive multifactorial treatment and cognitive functioning in screen-detected type 2 diabetes--the ADDITION-Netherlands study: a cluster-randomized trial.

AIM: To assess whether an intensive multifactorial treatment can reduce cognitive decrements and cognitive decline in screen-detected type 2 diabetes. METHODS: The multinational ADDITION-study, a cluster-randomized parallel group trial in patients with screen-detected type 2 diabetes, compared the effectiveness of intensive multifactorial treatment (IT; lifestyle advice and strict regulation of metabolic parameters) with routine care (RC) on cardiovascular outcome. In The Netherlands randomization was stratified according to practice organization. Allocation was concealed from patients. The present study assessed the effect of IT on cognition through two neuropsychological assessments (NPA) on two occasions. The assessments took place three and six years after the start of the intervention. Non-diabetic controls served as reference group. The first NPA was performed in 183 patients (IT: 97; RC: 86) and 69 controls. The second NPA was performed in 135 patients (IT: 71; RC: 64) and 55 controls. Primary outcome was a composite score, including the domains memory, information-processing speed and attention and executive function. Comparisons between the treatment groups were performed with multi-level analyses. RESULTS: The first NPA showed no differences between the treatment groups (mean difference composite z-score: 0.00; 95%-CI -0.16 to 0.16; IT vs RC). Over the next three years cognitive decline in the diabetic groups was within the range of the reference group and did not differ between the treatment arms (difference decline between diabetic groups -0.12; -0.24 to 0.01; IT vs RC). CONCLUSIONS: Six years of IT in screen-detected type 2 diabetes had no benefit on cognitive functioning over RC.