Brain microstructure is linked to cognitive fatigue in early multiple sclerosis.

Cognitive fatigue is a major symptom of Multiple Sclerosis (MS), from the early stages of the disease. This study aims to detect if brain microstructure is altered early in the disease course and is associated with cognitive fatigue in people with MS (pwMS) compared to matched healthy controls (HC). Recently diagnosed pwMS (N = 18, age < 45 years old) with either a Relapsing-Remitting or a Clinically Isolated Syndrome course of the disease, and HC (N = 19) matched for sex, age and education were analyzed. Quantitative multiparameter maps (MTsat, PD, R1 and R2*) of pwMS and HC were calculated. Parameters were extracted within the normal appearing white matter, cortical grey matter and deep grey matter (NAWM, NACGM and NADGM, respectively). Bayesian T-test for independent samples assessed between-group differences in brain microstructure while associations between score at a cognitive fatigue scale and each parameter in each tissue class were investigated with Generalized Linear Mixed Models. Patients exhibited lower MTsat and R1 values within NAWM and NACGM, and higher R1 values in NADGM compared to HC. Cognitive fatigue was associated with PD measured in every tissue class and to MTsat in NAWM, regardless of group. Disease-specific negative correlations were found in pwMS in NAWM (R1, R2*) and NACGM (R1). These findings suggest that brain microstructure within normal appearing tissues is already altered in the very early stages of the disease. Moreover, additional microstructure alterations (e.g. diffuse and widespread demyelination or axonal degeneration) in pwMS may lead to disease-specific complaint of cognitive fatigue.

Prolonged cognitive effort impairs inhibitory control and causes significant mental fatigue after an endurance session with an auditive distractor in professional soccer players.

BACKGROUND: Throughout official soccer matches, the presence of cheer by the crowd could be considered a critical auditive distraction that could further impair the cognitive interference control system, multiple object tracking (MOT) skill, heart rate variability (HRV), and increase mental fatigue. As the resource is not immediately replenished, the impairment of the cognitive interference control system may be delayed following a soccer game. Then, evaluating the recovery time course of the cognitive interference control system, MOT skill, HRV, and mental fatigue after prolonged tasks combining physical, endurance, and cognitive effort are essential. PURPOSE: We aimed to analyze the acute effect of cognitive effort and auditive distractor with 24-h follow-up throughout a prolonged endurance session on inhibitory control, subjective mental fatigue, MOT skill, and HRV in professional soccer players. METHODS: Twenty professional male soccer players were recruited (23.56 ± 3.8 years, 78.1 ± 6.9 kg, 1.77 ± 0.06 m, and 12.5 ± 5.3% body fat). The sessions were performed in a randomized and counterbalanced crossover design, divided into four experimental conditions: endurance, endurance + MOT, endurance + MOT + AD, and endurance + AD. The soccer players completed the incongruent Stroop task utilizing an eye-tracker to assess cognitive effort. MOT task, subjective mental fatigue, and HRV were evaluated before the endurance training (60%Δ of maximal aerobic velocity during 40-min) and after 30-min and 24-h of recovery. These sessions were designed to investigate the acute effect of prolonged cognitive effort (repeated MOT throughout the endurance task) and AD (constant crowd noise and coach's voice each 15-40 s, totalizing = 80 voices) on inhibitory control, MOT skills, HRV, and subjective mental fatigue after a fixed endurance training session. RESULTS: There was no condition × time interaction for accuracy of inhibitory control (p > 0.05, ηp2 = 0.001). There was a significant condition × time interaction for inhibitory control response time (p < 0.05, ηp2 = 0.16). A higher response time of inhibitory control was found for the endurance + MOT + AD and endurance + MOT experimental sessions (p < 0.05). There was a significant condition × time interaction for subjective mental fatigue (p < 0.05, ηp2 = 0.46). A higher subjective mental fatigue was found for the endurance + MOT + AD and endurance + MOT experimental sessions (p < 0.05). There was no condition × time interaction for HRV (p > 0.05, ηp2 = 0.02). CONCLUSION: We concluded that cognitive effort throughout a prolonged endurance session impaired inhibitory control and increased mental fatigue without promoting greater MOT skill and HRV changes in professional soccer players.

A likely association between low mannan-binding lectin level and brain fog onset in long COVID patients.

Brain fog can be described as a constellation of new-onset neuropsychiatric sequelae in the post-acute phase of COVID-19 (long COVID). The symptoms include inattention, short-term memory loss, and reduced mental acuity, which may undermine cognition, concentration, and sleep. This cognitive impairment, persisting for weeks or months after the acute phase of SARS-CoV-2 infection, can significantly impact on daily activities and the quality of life. An important role for the complement system (C) in the pathogenesis of COVID-19 has emerged since the beginning of pandemic outbreak. A number of pathophysiological characteristics including microangiopathy and myocarditis have been attributed to dysregulated C activation due to SARS-CoV-2 infection. Mannan-binding lectin (MBL), the first recognition subcomponent of the C lectin pathway, has been shown to bind to glycosylated SARS-CoV-2 spike protein, genetic variants of MBL2 are suggested to have an association with severe COVID-19 manifestations requiring hospitalization. In the present study, we evaluated MBL activity (lectin pathway activation) and levels in the sera of a cohort of COVID-19 patients, presenting brain fog or only hyposmia/hypogeusia as persistent symptoms, and compared them with healthy volunteers. We found significantly lower levels of MBL and lectin pathway activity in the sera of patients experiencing brain fog as compared to recovered COVID-19 patients without brain fog. Our data indicate that long COVID-associated brain fog can be listed among the variegate manifestations of increased susceptibility to infections and diseases contributed by MBL deficiency.

Post-acute sequelae of COVID-19 in young adults: Mental fatigue and decreased cognitive flexibility.

Background and purpose:

Post-acute sequelae of COVID-19 (PASC) describes the occurrence of persistent symptoms following COVID-19 infection. Neurological and psychiatric symptoms may include fatigue, post-exertional malaise, cognitive complaints, sensorimotor symptoms, headache, insomnia, depression, and post-traumatic stress disorder. The aim of this study was to evaluate the long-term effects of COVID-19 infection on mental fatigue and cognitive flexibility in young adults.

Simple random sampling method was used to enroll university students into the study between December 25 and 31, 2022. The time since active infection, central neurological findings (such as headache, dizziness, and loss of smell or taste), and the presence of lung involvement were recorded. The Mental Fatigue Scale (MFS) and the Cognitive Flexibility Inventory (CFI) were administered to all participants.

The study included 102 cases and 111 controls. The case group had a significantly higher total MFS score (12.95; 9.69 respectively) (p<0.001) and significantly lower total CFI score (100.01; 109.84 respectively) (p<0.001) than the control group. The case group experienced more frequent mental fatigue than the control group (p<0.001). Among all participants, a history of COVID-19 infection was identified as a risk factor for developing mental fatigue (odds ratio/OR: 2.74). In the case group, female sex (OR: 0.38) and lung involvement (OR: 10.74) were risk factors for developing mental fatigue.

This study demonstrates that COVID-19 infection might have long-term negative effects on cognitive health, likely due to a combination of organic and psychogenic mechanisms. 

Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.

INTRODUCTION: Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients. METHODS: One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI. RESULTS: Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network). CONCLUSIONS: Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.

A hypoarousal model of neurological post-COVID syndrome: the relation between mental fatigue, the level of central nervous activation and cognitive processing speed.

BACKGROUND: Knowledge on the nature of post-COVID neurological sequelae often manifesting as cognitive dysfunction and fatigue is still unsatisfactory. OBJECTIVES: We assumed that cognitive dysfunction and fatigue in post-COVID syndrome are critically linked via hypoarousal of the brain. Thus, we assessed whether tonic alertness as a neurocognitive index of arousal is reduced in these patients and how this relates to the level of central nervous activation and subjective mental fatigue as further indices of arousal. METHODS: 40 post-COVID patients with subjective cognitive dysfunction and 40 matched healthy controls underwent a whole-report paradigm of briefly presented letter arrays. Based on report performance and computational modelling according to the theory of visual attention, the parameter visual processing speed (VPS) was quantified as a proxy of tonic alertness. Pupillary unrest was assessed as a measure of central nervous activation. The Fatigue Assessment Scale was applied to assess subjective mental fatigue using the corresponding subscale. RESULTS: VPS was reduced in post-COVID patients compared to controls (p = 0.005). In these patients, pupillary unrest (p = 0.029) and mental fatigue (p = 0.001) predicted VPS, explaining 34% of the variance and yielding a large effect with f2 = 0.51. CONCLUSION: In post-COVID patients with subjective cognitive dysfunction, hypoarousal of the brain is reflected in decreased processing speed which is explained by a reduced level of central nervous activation and a higher level of mental fatigue. In turn, reduced processing speed objectifies mental fatigue as a core subjective clinical complaint in post-COVID patients.

The relationship between mental fatigue, depression, and cognition in Graves' disease.

Objective: Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves' disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism. Methods: A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment. Results: During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies. Conclusion: Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.

Cognitive and mental fatigue in chronic pain: cognitive functions, emotional aspects, biomarkers and neuronal correlates-protocol for a descriptive cross-sectional study.

INTRODUCTION: Chronic pain (CP) is one of the most frequently presenting conditions in health care and many patients with CP report mental fatigue and a decline in cognitive functioning. However, the underlying mechanisms are still unknown. METHODS AND ANALYSIS: This study protocol describes a cross-sectional study aimed at investigating the presence of self-rated mental fatigue, objectively measured cognitive fatigability and executive functions and their relation to other cognitive functions, inflammatory biomarkers and brain connectivity in patients with CP. We will control for pain-related factors such as pain intensity and secondary factors such as sleep disturbances and psychological well-being. Two hundred patients 18-50 years with CP will be recruited for a neuropsychological investigation at two outpatient study centres in Sweden. The patients are compared with 36 healthy controls. Of these, 36 patients and 36 controls will undergo blood sampling for inflammatory markers, and of these, 24 female patients and 22 female controls, between 18 and 45 years, will undergo an functional MRI investigation. Primary outcomes are cognitive fatigability, executive inhibition, imaging and inflammatory markers. Secondary outcomes include self-rated fatigue, verbal fluency and working memory. The study provides an approach to study fatigue and cognitive functions in CP with objective measurements and may demonstrate new models of fatigue and cognition in CP. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethics Review Board (Dnr 2018/424-31; 2018/1235-32; 2018/2395-32; 2019-66148; 2022-02838-02). All patients gave written informed consent to participate in the study. The study findings will be disseminated through publications in journals within the fields of pain, neuropsychology and rehabilitation. Results will be spread at relevant national and international conferences, meetings and expert forums. The results will be shared with user organisations and their members as well as relevant policymakers. TRIAL REGISTRATION NUMBER: NCT05452915.

Physical and mental fatigue in post-COVID syndrome and their associations over time: A small-sample ESM-study to explore fatigue, quality of sleep and behaviours.

OBJECTIVE: Post-COVID syndrome leaves millions of people with severe fatigue, yet little is known about its nature in daily life. In this exploratory study, momentary associations between physical and mental fatigue, quality of sleep and behaviours over two weeks in patients with post-COVID syndrome were assessed. METHOD: Data on fatigue levels, quality of sleep and behaviours was collected for 14 consecutive days using the experience sampling method in ten ex-hospitalised patients with post-COVID syndrome. RESULTS: Multilevel linear regression modelling showed strong associations between physical and mental fatigue (ß = 0.61, p ≤0.001), significant both between and within individuals. Sleeping more hours at night was associated with less physical and mental fatigue the following day (ß = -0.35, p = .001; ß = -0.27, p = .008). Strenuous relaxation (B = 0.45, p ≤0.001; B = 0.28, p = .004) and social contacts (B = -0.33, p = .003; B = -0.22, p = .02) were associated with physical and mental fatigue at the same measurement point. Performing household chores decreased physical and mental fatigue (B = -0.29, p = .02; B = -0.30, p = .006) two hours later on the same day, whereas eating and drinking increased physical fatigue (B = 0.20, p = .05) two hours later on the same day. CONCLUSION: Physical fatigue and mental fatigue were strongly associated and revealed fluctuations in fatigue levels between individuals, which might suggest potentially different post-COVID subgroups. Indications for potential risk and beneficial behaviours for fatigue were found.

Post-viral fatigue in COVID-19: A review of symptom assessment methods, mental, cognitive, and physical impairment.

Coronavirus 2 is responsible for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), and the main sequela is persistent fatigue. Post-viral fatigue is common and affects patients with mild, asymptomatic coronavirus disease-2019 (COVID-19). However, the exact mechanisms involved in developing post-COVID-19 fatigue remain unclear. Furthermore, physical and cognitive impairments in these individuals have been widely described. Therefore, this review aims to summarize and propose tools from a multifaceted perspective to assess COVID-19 infection. Herein, we point out the instruments that can be used to assess fatigue in long-term COVID-19: fatigue in a subjective manner or fatigability in an objective manner. For physical and mental fatigue, structured questionnaires were used to assess perceived symptoms, and physical and cognitive performance assessment tests were used to measure fatigability using reduced performance.

The moderation effects of task attributes and mental fatigue on post-interruption task performance in a concurrent multitasking environment.

In a concurrent multitasking environment, performing many types of tasks increases task complexity, and working long hours makes a person susceptible to mental fatigue. Emerging technologies may lead to more task interruptions. This study examines the effects of task attributes and mental fatigue on interrupted task performance in a concurrent multitasking environment. Thirty-four participants performed the MATB-Ⅱ under eight conditions (two-level task interruption, two-level task complexity, two-level fatigue). The results revealed the significant interaction effects of interruption × task complexity and of interruption × fatigue state. The findings show that more time is required to return to a complex primary task, and there are differences among subtask types. Mental fatigue negatively affects primary task performance, workload, and the resumption lag after an interruption. The findings are explained by the increasing information cues needed to resume complex tasks and the negative effect of fatigue on memory activation.

[Mental fatigue - possible explanations, diagnostic methods and possible treatments]. / Hjärntrötthet ­ ett osynligt gissel.

Mental fatigue or brain fatigue is a pathological and disabling symptom with diminished mental energy. It can be a long-lasting consequence after trauma or disease affecting the brain. The person can do most things in the moment and can be perceived as completely healthy, but the mental energy is insufficient over time and affects the ability to work and participate in social activities. After a conversation, for example, the person can be completely drained of energy and the recovery time is disproportionally long. Here we describe the phenomenon of mental fatigue, provide an explanatory model for how the condition can arise, point out diagnostic methods and possible treatments, which are currently in the research stage but may be implemented in healthcare within the foreseeable future.

Mental fatigue mediates the relationship between cognitive functions and return to productive activity following traumatic brain injury: a mediation analysis.

PURPOSE: We performed a mediation analysis to investigate how mental fatigue mediates the relationship between cognitive functions and the return to productive activity following TBI. METHODS: One hundred and one people (≥20 years) with first-time TBI more than 3 months who completed a series of cognitive tasks followed by Chinese versions of the Mental Fatigue Scale and Community Integration Questionnaire-Revised. Mediation analysis was used to test our hypotheses. RESULTS: Recognition memory and information processing speed were the only cognitive functions correlated with mental fatigue (B = -0.56 and -0.37, P = .04 and < 0.001) and the return to productive activity (B = 0.69 and 0.19, both P < .001) after controlling for confounders. Mental fatigue partially mediated the associations of recognition memory and information processing speed with the return to productive activity (B = 0.15 and 0.08, P = .001 and < 0.001, proportion of mediation = 22% and 46%) after the adjustment of confounders. CONCLUSIONS: The findings suggest that mental fatigue can partially mediate the relationship between cognitive deficits and return to productive activity. Mental fatigue can be considered a crucial, treatable mediator of the adverse effects of cognitive impairment upon return to productive activity following TBI.

Methylphenidate may improve mental fatigue in individuals with multiple sclerosis: A pilot clinical trial.

BACKGROUND: Fatigue is the most common symptom in multiple sclerosis (MS), previously attributed to dopamine imbalance. Evidence suggests that methylphenidate, a psychostimulant that increases striatal and prefrontal dopamine levels, is effective in reducing fatigue in various disorders. However, its effect on state vs. trait mental fatigue in MS is yet to be examined. METHODS: This pilot study investigates the efficacy of methylphenidate on decreasing self-reported mental fatigue in 12 individuals with MS in a double-blind, placebo-controlled, cross-over randomized clinical trial. RESULTS: Our results show that "state", but not "trait" MS-related fatigue, was reduced after 4 weeks of methylphenidate administration as compared to placebo.

Fatigue in men and women who have returned to work after stroke: Assessed with the Fatigue Severity Scale and Mental Fatigue Scale.

OBJECTIVE: To assess the occurrence of self-reported fatigue among men and women who have returned to work after stroke, and the association between 2 fatigue rating scales. DESIGN: A cross-sectional study. SUBJECTS: A total of 91 adults (58 men/33 women, mean age 53 years) with mild to moderate disability. METHODS: Questionnaires were posted to participants approximately one year after stroke. Fatigue was assessed with the Fatigue Severity Scale (FSS) and the Mental Fatigue Scale (MFS). RESULTS: In total, 58% of the women and 33% of the men reported fatigue on the FSS (total score ≥ 4), and 46% of the women and 28% of the men reported mental fatigue on the MFS (total score ≥ 10.5). Being easily fatigued, decreased motivation, mental fatigability and sensitivity to stress were the most reported problems. FSS and MFS were moderately associated (rho 0.517-0.732). CONCLUSION: Fatigue is common among persons who have returned to work after stroke, and interferes with daily life. The long-term consequences of fatigue should be addressed after stroke, especially in women. The FSS and the MFS can be used in combination, as they provide information on different aspects of fatigue.

Perceived mental strain dissociates from perceived physical strain during relative intensity submaximal exercise on ascent from low to high altitude.

Perceived fatigability, which has perception of physical strain and of mental strain as its components, can impact exercise tolerance. Upon ascent to high altitude, low landers experience reduced exercise capacity and reduced tolerance for a given absolute submaximal work rate. It is established that perceived physical strain tracks with relative exercise intensity. However, it is not known how altitude ascent affects perceived mental strain relative to perceived physical strain. We tested the hypothesis that when exercising at the same relative exercise intensity perceived physical strain will remain unchanged whereas perceived mental strain will decrease on ascent from low to high altitude in the Everest region in Nepal. Twelve hours after arriving at each of three elevations; 1400 m, 3440 m, and 4240 m, 12 untrained participants used the task effort awareness (TEA) and physical-rating of perceived exertion (P-RPE) scales to report perceived mental and physical strain during a 20 min walking test at a self-monitored heart rate reserve (HRR) range of 40-60% (Polar HR Monitor). TEA and P-RPE were recorded twice during exercise (5-7 min and 14-16 min). Neither P-RPE (1400 m: 11.1 ± 1.8, 3440 m: 10.7 ± 1.2, 4240 m: 11.5 ± 1.5) nor %HRR (1400 m: 55.25 ± 7.34, 3440 m: 51.70 ± 6.70, 4240 m: 50.17 ± 4.02) changed as altitude increased. TEA decreased at 4240 m (2.05 ± 0.71) compared to 1400 m (3.44 ± 0.84)--this change was not correlated with any change in %HRR nor was it due to a change in core affect. These findings support our hypothesis and demonstrate the independence of perceived physical and perceived mental strain components of perceived fatigability. Implications for exercise tolerance remain to be determined.

Mental Fatigue after Mild Traumatic Brain Injury in Relation to Cognitive Tests and Brain Imaging Methods.

Most people recover within months after a mild traumatic brain injury (TBI) or concussion, but some will suffer from long-term fatigue with a reduced quality of life and the inability to maintain their employment status or education. For many people, mental fatigue is one of the most distressing and long-lasting symptoms following an mTBI. No efficient treatment options can be offered. The best method for measuring fatigue today is with fatigue self-assessment scales, there being no objective clinical tests available for mental fatigue. The aim here is to provide a narrative review and identify fatigue in relation to cognitive tests and brain imaging methods. Suggestions for future research are presented.

Fatigue Following Pediatric Arterial Ischemic Stroke: Prevalence and Associated Factors.

Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children.

Neurological Outcome, Mental Fatigue, and Occurrence of Aneurysms >15 Years After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Long-term data on neurological and radiological outcome after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The aim of this study was to report neurological and radiological outcome >15 years after aSAH. METHODS: Patients with aSAH who were randomly assigned to endovascular treatment (EVT) or microsurgical treatment (MST) during 1997-2001 were included. Main end points were neurological outcome assessed by modified Rankin Scale, fatigue assessed by mental fatigue scale, and radiological outcome assessed by magnetic resonance angiography. Results for mental fatigue scale were compared with a control group. RESULTS: After 15-21 years, 46 (62.2%) of the 74 survivors replied to a questionnaire. Of these patients, 18 received MST, and 28 received EVT. Modified Rankin Scale score of 0-2 was found in 100% of patients in the EVT group and 88.8% of patients in the MST group. Moderate or severe mental fatigue was found in 7/28 patients (25%) in the EVT group and 7/18 patients (38.8%) in the MST group (P < 0.05), whereas moderate or severe mental fatigue was observed in 3/34 patients (8.9%) in the control group. Magnetic resonance angiography was performed in 29 patients. In the EVT group, new neck remnants were found in 2/16 patients (12.5%), and de novo aneurysm was found in 2/16 patients (12.5%). In the MST group, de novo aneurysm was found in 1/13 patients (7.7%). CONCLUSIONS: Neurological outcome at long-term follow-up after aSAH was good; however, mental fatigue was overrepresented in patients compared with healthy control subjects regardless of treatment modality. Residual or de novo aneurysm was found in 17% of patients warranting radiological long-term follow-up.