Serum and cerebrospinal fluid BDNF concentrations are associated with neurological and cognitive improvement in multiple sclerosis: A pilot study.

BACKGROUND: Biomarkers of disease activity have been intensively studied in multiple sclerosis (MS) but knowledge on predictors of disability improvement is limited. The aim of this pilot study was to explore whether increased brain-derived neurotrophic factor concentrations in serum and CSF (sBDNF/cBDNF) precede neurological and cognitive improvement in MS. METHODS: In this pilot, monocentric prospective cohort study we collected serum/CSF samples at baseline together with EDSS (n = 36) and cognitive testing (n = 34) in patients with relapsing-remitting/primary progressive MS or clinically isolated syndrome. BDNF was assessed in serum and CSF with a single molecule array (SIMOA) HD-1 analyser (Quanterix). Twelve months later EDSS and cognitive testing were repeated. BDNF concentrations of patients with vs. without disability or cognitive improvement (disability improvement: decrease in EDSS ≥ 0.5; cognitive improvement: average z-score increase in neuropsychological performance ≥ 0.5) were compared using univariate ANOVAs adjusting for covariates. RESULTS: Compared to subjects without, patients with disability improvement had higher sBDNF at baseline (q = 0.04). Subjects with cognitive improvement had higher cBDNF at baseline than those without cognitive improvement (q = 0.004). Secondary analysis demonstrated significant correlations between sBDNF and EDSS change (q = 0.036), cBDNF and average z-score change (q = 0.04) and cBDNF and number of cognitive tests with improvement (q = 0.04), while controlling for covariates. CONCLUSIONS: Our findings suggest a possible role for BDNF in neurological and cognitive improvement in MS. These findings have to be confirmed in a larger sample but they already highlight the potential of BDNF as a biomarker for disability improvement and neuroplasticity in MS.

Brain-derived neurotrophic factor and neurofilament light chain in cerebrospinal fluid are inversely correlated with cognition in Multiple Sclerosis at the time of diagnosis.

BACKGROUND: Cognitive performance may be impaired in MS even at the earliest stages of disease. We tested whether brain-derived neurotrophic factor and neurofilament light chain levels in serum and cerebrospinal fluid (CSF) samples (sNfL/cNfL/sBDNF/cBDNF) collected at the time of diagnosis are associated with cognitive performance. METHODS: We measured sNfL/cNfL/sBDNF/cBDNF using single-molecule array (Simoa) in 47 newly diagnosed patients (32 relapsing-remitting MS/6 primary progressive MS/9 clinically isolated syndrome). Partial correlations between average z-score on neuropsychological tests and sNfL/sBDNF/cNfL/cBDNF were computed after adjusting for covariates. Multivariate analysis of covariance determined the effect of cognitive status on biomarker levels. A composite measure of NfL and BDNF was submitted to similar exploratory analysis. RESULTS: Cognitive performance correlated inversely with cNfL (r=-0.451/q=0.032) and cBDNF (r=-0.406/q=0.034). Impairment in at least two different tests was linked to higher cNfL (p=0.011) and cBDNF (p=0.035) levels compared to impairment in only one test and for cNfL also compared to no impairment at all (p=0.01). Composite CSF biomarker measure accounting for both cNfL and cBDNF correlated more strongly with tests of information processing (p=0.048) and verbal learning/memory consolidation (p = 0.02) as compared to the single CSF biomarkers. CONCLUSIONS: CSF BDNF and NfL levels measured at the time of diagnosis are inversely associated with cognitive performance in MS. Our findings suggest that CSF biomarkers linked to different pathophysiological processes reflect neuropsychological impairment in the earliest stages of the disease. Combining different CSF measures might facilitate the developing of a better biomarker of cognition in MS.

Neurocognitive Outcome and Seizure Freedom After Awake Surgery of Gliomas.

Objectives: Gliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficits. First treatment choice for patients with gliomas in speech-related areas is awake surgery, which aims at maximizing tumor resection while preserving or improving patient's neurological status. The present study aimed at evaluating neurocognitive functioning and occurrence of epileptic seizures in patients suffering from gliomas located in language-related areas before and after awake surgery as well as during their follow up course of disease. Materials and Methods: In this prospective study we included patients who underwent awake surgery for glioma in the inferior frontal gyrus, superior temporal gyrus, or anterior temporal lobe. Preoperatively, as well as in the short-term (median 4.1 months, IQR 2.1-6.0) and long-term (median 18.3 months, IQR 12.3-36.6) postoperative course, neurocognitive functioning, neurologic status, the occurrence of epileptic seizures and number of antiepileptic drugs were recorded. Results: Between 09/2012 and 09/2019, a total of 27 glioma patients, aged 36.1 ± 11.8 years, were included. Tumor resection was complete in 15, subtotal in 6 and partial in 6 patients, respectively. While preoperatively impairment in at least one neurocognitive domain was found in 37.0% of patients, postoperatively, in the short-term, 36.4% of patients presented a significant deterioration in word fluency (p=0.009) and 34.8% of patients in executive functions (p=0.049). Over the long-term, scores improved to preoperative baseline levels. The number of patients with mood disturbances significantly declined from 66.7% to 34.8% after surgery (p=0.03). Regarding seizures, these were present in 18 (66.7%) patients prior to surgery. Postoperatively, 22 (81.5%) patients were treated with antiepileptic drugs with all patients presenting seizure-freedom. Conclusions: In patients suffering from gliomas in eloquent areas, the combination of awake surgery, regular neurocognitive assessment - considering individual patients´ functional outcome and rehabilitation needs - and the individual adjustment of antiepileptic therapy results in excellent patient outcome in the long-term course.

Visual Search in Naturalistic Scenes Reveals Impaired Cognitive Processing Speed in Multiple Sclerosis.

BACKGROUND: Standardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs. impaired information processing speed measured by the Symbol Digit Modalities Test (SDMT) differ in their visual search behavior during ecologically valid tasks reflecting everyday activities. METHODS: Forty-three patients with relapsing-remitting MS enrolled in an eye-tracking experiment consisting of a visual search task with naturalistic images. Patients were grouped into "impaired" and "unimpaired" according to their SDMT performance. Reaction time, accuracy and eye-tracking parameters were measured. RESULTS: The groups did not differ regarding age, gender, and visual acuity. Patients with impaired SDMT (cut-off SDMT-z-score < -1.5) performance needed more time to find and fixate the target (q = 0.006). They spent less time fixating the target (q = 0.042). Impaired patients had slower reaction times and were less accurate (both q = 0.0495) even after controlling for patients' upper extremity function. Exploratory analysis revealed that unimpaired patients had higher accuracy than impaired patients particularly when the announced target was in unexpected location (p = 0.037). Correlational analysis suggested that SDMT performance is inversely linked to the time to first fixation of the target only if the announced target was in its expected location (r = -0.498, p = 0.003 vs. r = -0.212, p = 0.229). CONCLUSION: Dysfunctional visual search behavior may be one of the mechanisms translating cognitive deficits into difficulties in everyday tasks in MS patients. Our results suggest that cognitively impaired patients search their visual environment less efficiently and this is particularly evident when top-down processes have to be employed.

Gender disparity in German neurosurgery.

OBJECTIVE: Despite the rising number of women in higher education and leadership positions, the proportional rise of female neurosurgeons still lags behind these fields. This study evaluates the gender distribution in German neurosurgical departments across all career levels, and is aimed at heightening the awareness of gender disparity and the need for improving gender equality and its related opportunities. METHODS: Data on gender distribution across all professional levels in German neurosurgical departments were obtained from departmental websites as well as by email and telephone request. Results were additionally analyzed in reference to hospital ownership type of the neurosurgical departments. RESULTS: A total of 140 German neurosurgical departments employing 2324 neurosurgeons were evaluated. The analysis revealed a clear preponderance of men in leadership positions. Only 9 (6.3%) of 143 department heads were women, and there were only 1 (2.4%), 17 (14.5%), and 4 (12.5%) women among 42 vice-directors, 117 chief senior physicians, and 32 managing senior physicians, respectively. Senior physicians not holding a leadership position were female in 23.1%, whereas board-certified neurosurgeons not holding a senior physician position and residents were female in 33.6% and 35.0%, respectively. Of note, the highest proportion of female department heads (15.6%) was found in private hospitals. CONCLUSIONS: The number of women in leadership positions in German neurosurgical departments is dramatically low, and with increasing leadership status gender disparity increases. Mentorship, recruitment, the perception of benefits offered by diversity and programs facilitating gender equality, job sharing, parental leave policies, and onsite childcare programs are needed to turn German neurosurgical departments into modern medical departments reflecting the gender profile of the general patient population.

C-Reactive Protein Levels and Gadolinium-Enhancing Lesions Are Associated With the Degree of Depressive Symptoms in Newly Diagnosed Multiple Sclerosis.

Background: Inflammation is essential for the pathogenesis of multiple sclerosis (MS). While the immune system contribution to the development of neurological symptoms has been intensively studied, inflammatory biomarkers for mental symptoms such as depression are poorly understood in the context of MS. Here, we test if depression correlates with peripheral and central inflammation markers in MS patients as soon as the diagnosis is established. Methods: Forty-four patients were newly diagnosed with relapsing-remitting MS, primary progressive MS or clinically isolated syndrome. Age, gender, EDSS, C-reactive protein (CRP), albumin, white blood cells count in cerebrospinal fluid (CSF WBC), presence of gadolinium enhanced lesions (GE) on T1-weighted images and total number of typical MS lesion locations were included in linear regression models to predict Beck Depression Inventory (BDI) score and the depression dimension of the Symptoms Checklist 90-Revised (SCL90RD). Results: CRP elevation and GE predicted significantly BDI (CRP: p = 0.007; GE: p = 0.019) and SCL90RD (CRP: p = 0.004; GE: p = 0.049). The combination of both factors resulted in more pronounced depressive symptoms (p = 0.04). CSF WBC and EDSS as well as the other variables were not correlated with depressive symptoms. Conclusions: CRP elevation and GE are associated with depressive symptoms in newly diagnosed MS patients. These markers can be used to identify MS patients exhibiting a high risk for the development of depressive symptoms in early phases of the disease.

Executive deficits in neuropsychological testing differentiate between autoimmune temporal lobe epilepsy caused by limbic encephalitis and temporal lobe epilepsies with non-autoimmune etiologies.

OBJECTIVE: Patients with temporal lobe epilepsy caused by autoimmune limbic encephalitis (AI-TLE) clinically resemble patients with temporal lobe epilepsy with non-autoimmune etiologies (NAI-TLE) but have a different prognosis and require specific adjusted therapies. The objective of this study was to investigate whether patients with these forms of TLE can be discerned by means of neuropsychological assessment. METHODS: Data from 103 patients with TLE (n = 39 with AI-TLE and n = 64 with NAI-TLE, including n = 39 with hippocampal sclerosis [HS] and n = 25 with low-grade epilepsy-associated tumors [LEAT]) and 25 healthy controls who underwent comprehensive neuropsychological assessments were analyzed retrospectively. The neuropsychological characteristics (mean z-scores) were compared between groups using one-way ANOVA, independent-samples t-tests, and discriminant function analysis (DFA). RESULTS: The groups of patients with TLE showed significantly lower performance in attentional, visuospatial, verbal memory, and nonverbal memory functions compared to the healthy controls. Solely in the domain of executive functions, patients with AI-TLE showed significantly lower performance compared to patients with NAI-TLE regarding cognitive flexibility (p = 0.002) and verbal fluency (p = 0.018). Moreover, the DFA identified cognitive flexibility to be most appropriate to differentiate between patients with AI-TLE and patients with HS. Group membership was correctly predicted through neuropsychological assessment alone in 66.7% of the patients using cross-validation. SIGNIFICANCE: We were able to identify specific neuropsychological features in our sample of patients with AI-TLE. While all groups of patients with TLE showed the expected TLE-typical memory impairments, significant differences between patients with AI-TLE and NAI-TLE were present only in the cognitive domain of executive functions. This finding facilitates the choice of suitable psychometric tests in clinical routine and, thus, the clinical differential diagnosis between these entities.

Neurocognitive deficits in patients suffering from glioma in speech-relevant areas of the left hemisphere.

OBJECTIVE: Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere. METHODS: Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study. Cognitive performances were analyzed regarding an influence of patient characteristics and tumor localization. RESULTS: Severe impairment in at least one neurocognitive domain was found in 36 (83.7%) patients. Anxiety and depression were observed most frequently, followed by verbal memory impairments. Verbal memory was more strongly affected in patients with ATL or pST/SMG tumors compared to IFG tumors (p = 0.004 and p = 0.013, resp.). Overall, patients suffering from tumors in the ATL were most frequently and severely impaired. CONCLUSION: Patients suffering from gliomas involving different regions within the language dominant hemisphere frequently present impairments in neurocognitive domains also other than language. Considering individual functions at risk may help in better advising patients prior to treatment and in tailoring the individual therapeutic strategy to preserve patients' quality of life.

Wada test results contribute to the prediction of change in verbal learning and verbal memory function after temporal lobe epilepsy surgery.

In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients' verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p = .032) and verbal memory function (∆R2 = 0.386, p = .005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications.

Impact of psychiatric distress and physical disability on quality of life in neuromyelitis optica spectrum disorder and chronic autoimmune demyelinating polyneuropathies.

BACKGROUND: Determinants of quality of life (QoL) in demyelinating disorders have been investigated predominantly for multiple sclerosis, especially with regard to "soft clinical signs" such as psychiatric distress. In this exploratory study, we aimed to identify common determinants of QoL for both central and peripheral demyelination in the understudied disease entities of neuromyelitis optica spectrum disorder (NMOSD) and chronic autoimmune demyelinating polyneuropathy (CADP). METHODS: 20 NMOSD and 16 CADP patients were evaluated for physical disability (EDSS and INCAT ODSS), cognitive dysfunction (neuropsychological test battery), psychiatric distress (SCL-90-R), depression (BDI), fatigue (FSMC) and quality of life (EQ-5D-3 L). A linear regression with QoL as a dependent variable and clinical parameters and demographic covariates as independent variables was computed. Additionally, a multivariate analysis of variance was computed to investigate whether NMOSD and CADP differed with regard to QoL and clinical parameters. RESULTS: Physical disability and psychiatric distress affected QoL in both NMOSD and CADP with a stronger effect for psychiatric distress in comparison to physical disability, as indicated by the higher standardized beta coefficient for psychiatric distress (b = -0.540; p = 0.002 vs. b = -0.614; p = 0.028). NMOSD reported higher subjective well-being than CADP patients (F = 6.845, p = 0.015) while having similar physical disability, cognitive dysfunction, psychiatric distress, depression and fatigue and after having accounted for the influence of age, gender, education and disease duration. CONCLUSIONS: Our findings suggest that physical disability and psychiatric distress above all clinical factors affect QoL in patients with NMOSD and CADP. Addressing adequately this aspect in demyelinating diseases would contribute to a better QoL in these patients. Furthermore, higher subjective well-being scores for NMOSD than CADP might be attributable to the distinct immunomodulatory therapy regimens and course (relapse-driven vs. chronic) of the two diseases.

Assessing Cognitive Change and Quality of Life 12 Months After Epilepsy Surgery-Development and Application of Reliable Change Indices and Standardized Regression-Based Change Norms for a Neuropsychological Test Battery in the German Language.

OBJECTIVE: The establishment of patient-centered measures capable of empirically determining meaningful cognitive change after surgery can significantly improve the medical care of epilepsy patients. Thus, this study aimed to develop reliable change indices (RCIs) and standardized regression-based (SRB) change norms for a comprehensive neuropsychological test battery in the German language. METHODS: Forty-seven consecutive patients with temporal lobe epilepsy underwent neuropsychological assessments, both before and 12 months after surgery. Practice-effect-adjusted RCIs and SRB change norms for each test score were computed. To assess their usefulness, the presented methods were applied to a clinical sample, and binary logistic regression analyses were conducted to model the odds of achieving improvement in quality of life (QOL) after surgery. RESULTS: The determined RCIs at 90% confidence intervals and the SRB equations for each test score included in the test battery are provided. Cohen's kappa analyses revealed a moderate mean agreement between the two measures, varying from slight to almost perfect agreement across test scores. Using these measures, a negative association between improvement in QOL and decline in verbal memory functions after surgery was detected (adjusted odds ratio = 0.09, p = 0.006). SIGNIFICANCE: To the best of our knowledge, this study is the first to develop RCIs and SRB change norms necessary for the objective determination of neuropsychological change in a comprehensive test battery in the German language, facilitating the individual monitoring of improvement and decline in each patients' cognitive functioning and psychosocial situations after epilepsy surgery. The application of the described measures revealed a strong negative association between improvement in QOL and decline in verbal memory functions after surgery.

Benefits of glioma resection in the corpus callosum.

Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating the corpus callosum rarely undergo tumor resection and mostly present in a poor neurological state. We aimed at investigating the benefit of glioma resection in the corpus callosum, hypothesizing neuropsychological deficits were mainly caused by tumor presence. Between 01/2017 and 1/2020, 21 patients who underwent glioma resection in the corpus callosum were prospectively enrolled into this study. Neuropsychological function was assessed preoperatively, before discharge and after 6 months. Gross total tumor resection was possible in 15 patients, and in 6 patients subtotal tumor resection with a tumor reduction of 97.7% could be achieved. During a median observation time of 12.6 months 9 patients died from glioblastoma after a median of 17 months. Preoperatively, all cognitive domains were affected in up to two thirds of patients, who presented a median KPS of 100% (range 60-100%). After surgery, the proportion of impaired patients increased in all neurocognitive domains. Most interestingly, after 6 months, significantly fewer patients showed impairments in attention, executive functioning, memory and depression, which are domains considered crucial for everyday functionality. Thus, the results of our study strongly support our hypothesis that in patients with gliomas infiltrating the corpus callosum the benefit of tumor resection might outweigh morbidity.

The ability to return to work: a patient-centered outcome parameter following glioma surgery.

BACKGROUND: With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. METHODS: We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients' professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. RESULTS: We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21-63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11-82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2-22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work. CONCLUSION: The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.

Patients with chronic autoimmune demyelinating polyneuropathies exhibit cognitive deficits which might be associated with CSF evidence of blood-brain barrier disturbance.

BACKGROUND: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease. METHODS: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established. RESULTS: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates. CONCLUSIONS: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.

Factorial validity of a neuropsychological test battery and its ability to discern temporal lobe epilepsy from frontal lobe epilepsy - A retrospective study.

PURPOSE: Firstly, to evaluate the validity of a neuropsychological test battery in epilepsy patients, i.e. whether its tests sufficiently allow the assessment of the required cognitive domains in this specific group. Secondly, to examine its ability to differentiate between cognitive profiles of different subgroups of focal epilepsy. METHODS: The test battery suggested by the German ILAE Chapter was performed on 207 epilepsy patients, and its factor structure was investigated by principal component analysis (PCA). To further examine its accuracy in two matched subgroups of patients with temporal lobe epilepsy (TLE, n = 35) and frontal lobe epilepsy (FLE, n = 35), a discriminant function analysis (DFA) was used. RESULTS: PCA revealed eleven interpretable factors, accounting for 69.1% of total variance: Divided Attention, Reaction Time, Verbal Learning, Verbal Memory, Contextual Memory, Short-term- and Working Memory, Visuospatial Functioning, Space Perception, Verbal Fluency, Response Monitoring and Cognitive Flexibility. DFA identified six test to be most appropriate to discern TLE from FLE: WMS-IV Logical Memory, recognition; WMS-R Digit Span, backwards; VLMT, repetitions; VOSP Silhouettes; VLMT, delayed recall; and RWT Phonemic verbal fluency. Group membership was correctly predicted for 78.6% of patients using cross-validation. CONCLUSIONS: As neuropsychological assessments are central in clinical decision-making in presurgical work-up of epilepsy patients, the appropriateness of the test battery in use is essential. The majority of cognitive domains are sufficiently measurable by the test battery and it is highly sensitive to differentiate between the cognitive profiles of TLE and FLE. However, the selection of tests assessing nonverbal memory functions requires further improvement.

Cognitive Impairment in Multiple Sclerosis Is Reflected by Increased Susceptibility to the Sound-Induced Flash Illusion.

Objective: To determine whether the performance of multiple sclerosis (MS) patients in the sound-induced flash illusion (SiFi), a multisensory perceptual illusion, would reflect their cognitive impairment. Methods: We performed the SiFi task as well as an extensive neuropsychological testing in 95 subjects [39 patients with relapse-remitting MS (RRMS), 16 subjects with progressive multiple sclerosis (PMS) and 40 healthy control subjects (HC)]. Results: MS patients reported more frequently the multisensory SiFi than HC. In contrast, there were no group differences in the control conditions. Essentially, patients with progressive type of MS continued to perceive the illusion at stimulus onset asynchronies (SOA) that were more than three times longer than the SOA at which the illusion was already disrupted for healthy controls. Furthermore, MS patients' degree of cognitive impairment measured with a broad neuropsychological battery encompassing tests for memory, attention, executive functions, and fluency was predicted by their performance in the SiFi task for the longest SOA of 500 ms. Conclusions: These findings support the notion that MS patients exhibit an altered multisensory perception in the SiFi task and that their susceptibility to the perceptual illusion is negatively correlated with their neuropsychological test performance. Since MS lesions affect white matter tracts and cortical regions which seem to be involved in the transfer and processing of both crossmodal and cognitive information, this might be one possible explanation for our findings. SiFi might be considered as a brief, non-expensive, language- and education-independent screening test for cognitive deficits in MS patients.

Determinants of quality of life in relapsing-remitting and progressive multiple sclerosis.

BACKGROUND: Numerous factors can affect multiple sclerosis (MS) patients' quality of life (QoL). We investigated how physical impairment, upper extremity function, cognitive impairment, cognitive reserve, symptoms of psychological distress, depression, fatigue as well as age and disease duration contribute to patient-reported measures of QoL in relapse-remitting MS (RRMS) and progressive MS (PMS). METHODS: 39 patients with RRMS and 16 patients with PMS were evaluated for physical impairment (EDSS assessed by a neurologist), upper extremity function (9-hole peg test), cognitive deficits (broad neuropsychological test battery), cognitive reserves (highest obtained degree of education and vocabulary), symptoms of psychological distress (Symptom Checklist-90-R), depression (Beck Depression Inventory) and fatigue (Fatigue Scale for Motor and Cognitive Functions). The effects of these variables on QoL, as measured with the EQ-5D-3L, were tested with a multivariate analysis of variance. RESULTS: Degree of education, MS disease type, disease duration, BDI and SCL-90-R-scores affected significantly the EQ-5D index. Post-hoc analysis revealed that patients with university education, RRMS, shorter disease duration as well as less depression and psychological distress symptoms had significantly higher EQ-5D indices. No significant effects were observed for measures of physical disability, cognitive impairment or fatigue. CONCLUSIONS: Depression and psychological distress symptoms are among the factors with the most essential impact on subjective well-being in MS patients. Since they can be targeted by both psychopharmacological and psychotherapeutic treatment, focusing on mental comorbidity could substantially increase QoL in MS.

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering.

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speaking-related functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12.

The challenge of forgetting: Neurobiological mechanisms of auditory directed forgetting.

Directed forgetting (DF) is considered an adaptive mechanism to cope with unwanted memories. Understanding it is crucial to develop treatments for disorders in which thought control is an issue. With an item-method DF paradigm in an auditory form, the underlying neurocognitive processes that support auditory DF were investigated. Subjects were asked to perform multi-modal encoding of word-stimuli before knowing whether to remember or forget each word. Using functional magnetic resonance imaging, we found that DF is subserved by a right frontal-parietal-cingulate network. Both qualitative and quantitative analyses of the activation of this network show converging evidence suggesting that DF is a complex process in which active inhibition, attentional switching, and working memory are needed to manipulate both unwanted and preferred items. These results indicate that DF is a complex inhibitory mechanism which requires the crucial involvement of brain areas outside prefrontal regions to operate over attentional and working memory processes. Hum Brain Mapp 39:249-263, 2018. © 2017 Wiley Periodicals, Inc.