Return to work after aneurysmal subarachnoid hemorrhage.

Introduction: Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often recover without severe physical or cognitive deficits. However, strikingly low levels of engagement in productive employment have also been reported in aSAH patients with good or excellent outcomes. Knowledge about return to work (RTW) after aSAH and predictors of no RTW remain limited and controversial. The study aimed to delineate the return to maximum work capacity up to 5 years after the ictus in a larger number of consecutive aSAH patients from the entire aSAH severity spectrum and to identify demographic and medical predictors of no RTW. Methods: Data were acquired from a prospective institutional database. We included all 500 aSAH survivors aged > 18 years who were treated between January 2012 and March 2018. In addition to gathering data on work status and the type of work at ictus, we retrieved demographical data and assessed aSAH severity based on the quantification of subarachnoid, intraventricular, and intraparenchymal blood (ICH), as well as the World Federation of Neurological Societies (WFNS) grade. We registered the mode of aneurysm repair (endovascular or surgical) and recorded complications such as vasospasm, newly acquired cerebral infarctions, and chronic hydrocephalus. Results: Furthermore, work status and the grade of fatigue at follow-up were registered. RTW was assessed among 299 patients who were employed at ictus. Among them, 63.2% were women, and their age was 51.3 ± 9.4 (20-71) years. Return to gainful employment was 51.2%, with complete RTW accounting for 32.4%. The independent predictors of no RTW at ictus were age, the WFNS grade 3, and active smoking. The strongest independent predictor was the presence of clinically significant fatigue, which increased the risk of not returning to work by 5-fold. The chance to return to gainful employment significantly increased with the individual's years of education prior to their hemorrhage. The mode of aneurysm repair was not relevant with regard to RTW. Patients in the WFNS grades 1-2 more often returned to work than those in the WFNS grades 3-5, but our results indicate that neurological motor deficits are linked closer to no RTW than aSAH severity per se. Conclusion: Fatigue needs to be addressed as an important element on the path to return to work integration.

Coping strategies in patients with good outcome but chronic fatigue after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Fatigue is a highly prevalent and debilitating symptom among patients in the chronic phase of aneurysmal subarachnoid haemorrhage (aSAH) with no identified effective treatment. Cognitive therapy has been shown to have moderate effects on fatigue. Delineating the coping strategies used by patients with post-aSAH fatigue and relating them to fatigue severity and emotional symptoms could be a step towards developing a behavioural therapy for post-aSAH fatigue. METHODS: Ninety-six good outcome patients with chronic post-aSAH fatigue answered the questionnaires Brief COPE, (a questionnaire defining 14 coping strategies and three Coping Styles), the Fatigue Severity Scale (FSS), Mental Fatigue Scale (MFS), Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory (BAI). The Brief COPE scores were compared with fatigue severity and emotional symptoms of the patients. RESULTS: The prevailing coping strategies were "Acceptance", "Emotional Support", "Active Coping" and "Planning". "Acceptance" was the sole coping strategy that was significantly inversely related to levels of fatigue. Patients with the highest scores for mental fatigue and those with clinically significant emotional symptoms applied significantly more maladaptive avoidant strategies. Females and the youngest patients applied more "Problem-Focused" strategies. CONCLUSION: A therapeutic behavioural model aiming at furthering "Acceptance" and reducing passivity and "Avoidant" strategies may contribute to alleviate post-aSAH fatigue in good outcome patients. Given the chronic nature of post-aSAH fatigue, neurosurgeons may encourage patients to accept their new situation so that they can start a process of positive reframing instead of being trapped in a spiral of futile loss of energy and secondary increased emotional burden and frustration.

(-)-OSU6162 in the treatment of fatigue and other sequelae after aneurysmal subarachnoid hemorrhage: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: Fatigue after aneurysmal subarachnoid hemorrhage (aSAH) is common and usually long-lasting, and it has a considerable negative impact on health-related quality of life (HRQOL), social functioning, and the ability to return to work (RTW). No effective treatment exists. The dopaminergic regulator (-)-OSU6162 has shown promising results regarding the mitigation of fatigue in various neurological diseases, and therefore the authors aimed to investigate the efficacy of (-)-OSU6162 in alleviating fatigue and other sequelae after aSAH. METHODS: A double-blind, randomized, placebo-controlled, single-center trial was performed in which 96 participants with post-aSAH fatigue were administered 30-60 mg/day of (-)-OSU6162 or placebo over a period of 12 weeks. Efficacy was assessed using the Fatigue Severity Scale (FSS), the Mental Fatigue Scale (MFS), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II), the SF-36 questionnaire, and a neuropsychological test battery. Assessments were performed at baseline, after 1, 4, 8, and 12 weeks of treatment, and at follow-up, 8 weeks after treatment. RESULTS: The 96 participants with post-aSAH fatigue were randomized to treatment with (-)-OSU6162 (n = 49) or placebo (n = 47). The FSS, MFS, and BDI scores improved significantly in both groups after 12 weeks of treatment, whereas the BAI scores improved in the placebo group only. HRQOL improved significantly in the SF-36 domain "Vitality" in both groups. Neuropsychological test performances were within the normal range at baseline and not affected by treatment. The FSS score was distinctly improved in patients with complete RTW upon treatment with (-)-OSU6162. Concomitant use of antidepressants improved the efficacy of (-)-OSU6162 on the FSS score at week 1 beyond the placebo response, and correspondingly the use of beta- or calcium-channel blockers improved the (-)-OSU6162 efficacy beyond the placebo response in MFS scores at week 4 of treatment. There was a significant correlation between improvement in FSS, BAI, and BDI scores and the plasma concentration of (-)-OSU6162 at the dose of 60 mg/day. No serious adverse events were attributable to the treatment, but dizziness was reported more often in the (-)-OSU6162 group. CONCLUSIONS: Fatigue and other sequelae after aSAH were similarly alleviated by treatment with (-)-OSU6162 and placebo. (-)-OSU6162 improved fatigue, as measured with the FSS score, significantly in patients with complete RTW. There seemed to be synergetic effects of (-)-OSU6162 and medications interfering with dopaminergic pathways that should be explored further. The strong placebo response may be exploited in developing nonpharmacological treatment programs for post-aSAH fatigue.

Fatigue After Aneurysmal Subarachnoid Hemorrhage: Clinical Characteristics and Associated Factors in Patients With Good Outcome.

Fatigue after aneurysmal subarachnoid hemorrhage (post-aSAH fatigue) is a frequent, often long-lasting, but still poorly studied sequel. The aim of the present study was to characterize the nature of post-aSAH fatigue with an itemized analysis of the Fatigue Severity Scale (FSS) and Mental Fatigue Scale (MFS). We further wanted to assess the association of fatigue with other commonly observed problems after aSAH: mood disorders, cognitive problems, health-related quality of life (HRQoL), weight gain, and return to work (RTW). Ninety-six good outcome aSAH patients with fatigue completed questionnaires measuring fatigue, depression, anxiety, and HRQoL. All patients underwent a physical and neurological examination. Cognitive functioning was assessed with a neuropsychological test battery. We also registered prior history of fatigue and mood disorders as well as occupational status and RTW. The patients experienced fatigue as being among their three most disabling symptoms and when characterizing their fatigue they emphasized the questionnaire items "low motivation," "mental fatigue," and "sensitivity to stress." Fatigue due to exercise was their least bothersome aspect of fatigue and weight gain was associated with depressive symptoms rather than the severity of fatigue. Although there was a strong association between fatigue and mood disorders, especially for depression, the overlap was incomplete. Post-aSAH fatigue related to reduced HRQoL. RTW was remarkably low with only 10.3% of patients returning to their previous workload. Fatigue was not related to cognitive functioning or neurological status. Although there was a strong association between fatigue and depression, the incomplete overlap supports the notion of these two being distinct constructs. Moreover, post-aSAH fatigue can exist without significant neurological or cognitive impairments, but is related to reduced HRQoL and contributes to the low rate of RTW.

Prevalence and predictors of fatigue after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Fatigue is a common and disabling sequel after aneurysmal subarachnoid hemorrhage (aSAH). At present, prevalence estimates of post-aSAH fatigue in the chronic phase are scarce and vary greatly. Factors from the acute phase of aSAH have hitherto barely been associated with post-aSAH fatigue in the chronic phase. METHODS: Prospective study assessing prevalence of fatigue using the Fatigue Severity Scale (FSS) in patients who were living independently 1 to 7 years after aSAH. We compared demographic, medical, and radiological variables from the acute phase of aSAH between patients with and without fatigue (FSS ≥ 4 versus < 4) and searched for predictors of fatigue among these variables applying univariable and multivariable regression analyses. RESULTS: Of 726 patients treated for aSAH in the period between January 2012 and December 2017, 356 patients completed the assessment. The mean FSS score was 4.7 ± 1.7, and fatigue was present in 69.7%. The frequency of patients with fatigue did not decline significantly over time. Univariable analysis identified nicotine use, loss of consciousness at ictus (LOCi), rebleed prior to aneurysm repair, reduced consciousness to Glasgow Coma Scale (GCS) < 14, large amounts of subarachnoid blood, the presence of acute hydrocephalus, and severe vasospasm as factors that were significantly associated with fatigue. In multivariable analysis, nicotine use, reduced GCS, and severe vasospasm were independent predictors that all more than doubled the risk to develop post-aSAH fatigue. CONCLUSIONS: Fatigue is a frequent sequel persisting several years after aSAH. Nicotine use, reduced consciousness at admission, and severe vasospasm are independent predictors of fatigue from the acute phase of aSAH. We propose inflammatory cytokines causing dopamine imbalance to be a common denominator for post-aSAH fatigue and the presently identified predictors.

Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans.

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11-24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1-13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident-intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors' sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

[Posterior cortical atrophy]. / Posterior kortikal atrofi.

BACKGROUND: Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition. METHOD: The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group. RESULTS: Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful. INTERPRETATION: Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.