Dexamethasone versus Surgery for Chronic Subdural Hematoma.

BACKGROUND: The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear. METHODS: In this multicenter, open-label, controlled, noninferiority trial, we randomly assigned symptomatic patients with chronic subdural hematoma in a 1:1 ratio to a 19-day tapering course of dexamethasone or to burr-hole drainage. The primary end point was the functional outcome at 3 months after randomization, as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Noninferiority was defined by a lower limit of the 95% confidence interval of the odds ratio for a better functional outcome with dexamethasone than with surgery of 0.9 or more. Secondary end points included scores on the Markwalder Grading Scale of symptom severity and on the Extended Glasgow Outcome Scale. RESULTS: From September 2016 through February 2021, we enrolled 252 patients of a planned sample size of 420; 127 were assigned to the dexamethasone group and 125 to the surgery group. The mean age of the patients was 74 years, and 77% were men. The trial was terminated early by the data and safety monitoring board owing to safety and outcome concerns in the dexamethasone group. The adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months with dexamethasone than with surgery was 0.55 (95% confidence interval, 0.34 to 0.90), which failed to show noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of the results of the primary analysis. Complications occurred in 59% of the patients in the dexamethasone group and 32% of those in the surgery group, and additional surgery was performed in 55% and 6%, respectively. CONCLUSIONS: In a trial that involved patients with chronic subdural hematoma and that was stopped early, dexamethasone treatment was not found to be noninferior to burr-hole drainage with respect to functional outcomes and was associated with more complications and a greater likelihood of later surgery. (Funded by the Netherlands Organization for Health Research and Development and others; DECSA EudraCT number, 2015-001563-39.).

Unraveling the interplay between daily life fatigue and physical activity after subarachnoid hemorrhage: an ecological momentary assessment and accelerometry study.

BACKGROUND: Fatigue is one of the most commonly reported symptoms after subarachnoid hemorrhage (SAH) and is indirectly associated with physical activity (PA). Associations between fatigue and PA are primarily examined based on conventional measures (i.e. a single fatigue score or average PA levels), thereby assuming that fatigue and PA do not fluctuate over time. However, levels of fatigue and PA may not be stable and may interrelate dynamically in daily life. Insight in direct relationships between fatigue and PA in daily life, could add to the development of personalized rehabilitation strategies. Therefore we aimed to examine bidirectional relationships between momentary fatigue and PA in people with SAH. METHODS: People (n = 38) with SAH who suffer from chronic fatigue were included in an observational study using Ecological Momentary Assessment (EMA) and accelerometry. Momentary fatigue was assessed on a scale from 1 to 7 (no to extreme fatigue), assessed with 10-11 prompts per day for 7 consecutive days using EMA with a mobile phone. PA was continuously measured during this 7-day period with a thigh-worn Activ8 accelerometer and expressed as total minutes of standing, walking, running and cycling in a period of 45 min before and after a momentary fatigue prompt. Multilevel mixed model analyses including random effects were conducted. RESULTS: Mean age was 53.2 years (SD = 13.4), 58% female, and mean time post SAH onset was 9.5 months (SD = 2.1). Multilevel analyses with only time effects to predict fatigue and PA revealed that fatigue significantly (p < 0.001) increased over the day and PA significantly (p < 0.001) decreased. In addition, more PA was significantly associated with higher subsequent fatigue (ß = 0.004, p < 0.05) and higher fatigue was significantly associated with less subsequent PA (ß=-0.736, p < 0.05). Moreover, these associations significantly differed between participants (p < 0.001). CONCLUSIONS: By combining EMA measures of fatigue with accelerometer-based PA we found that fatigue and PA are bidirectionally associated. In addition, these associations differ among participants. Given these different bidirectional associations, rehabilitation aimed at reducing fatigue should comprise personalized strategies to improve both fatigue and PA simultaneously, for example by combining exercise therapy with cognitive behavioral and/or energy management therapy.

Corticosteroid treatment compared with surgery in chronic subdural hematoma: a systematic review and meta-analysis.

BACKGROUND: There is an ongoing debate on the role of corticosteroids in the treatment of chronic subdural hematoma (CSDH). This study aims to evaluate the effectiveness of corticosteroids for the treatment of CSDH compared to surgery. METHOD: A systematic search was performed in relevant databases up to January 2019 to identify RCTs or observational studies that compared at least two of three treatment modalities: the use of corticosteroids as a monotherapy (C), corticosteroids as an adjunct to surgery (CS), and surgery alone (S). Outcome measures were good neurological outcome, need for reintervention, mortality, and complications. Effect estimates were pooled and presented as relative risk (RR) with 95% confidence interval (95%CI). RESULTS: Of 796 initially identified studies, 7 were included in the meta-analysis. Risk of bias was generally high. There were no differences in good neurological outcome between treatment modalities. The need for reintervention varied between 4 and 58% in C, 4-12% in CS, and 7-26% in S. The need for reintervention was lower in CS compared with C (RR 3.34 [95% CI 1.53-7.29]; p < 0.01) and lower in CS compared with S (RR 0.44 [95% CI 0.27-0.72]; p < 0.01). Mortality varied between 0 and 4% in C, 0-13% in CS, and 0-44% in S. Mortality was lower in CS compared with S (RR 0.39 [95% CI 0.25-0.63]; p < 0.01). There were no differences in complications between treatment modalities. CONCLUSIONS: This meta-analysis suggests that the addition of corticosteroids to surgery might be effective in the treatment of CSDH. However, the results must be interpreted with caution in light of the serious risk of bias of the included studies. This study stresses the need for large randomized trials to investigate the use of corticosteroids in the management of CSDH.

Inactive lifestyles and sedentary behavior in persons with chronic aneurysmal subarachnoid hemorrhage: evidence from accelerometer-based activity monitoring.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (a-SAH) is a potential life-threatening stroke. Because survivors may be at increased risk for inactive and sedentary lifestyles, this study evaluates physical activity (PA) and sedentary behavior (SB) in the chronic phase after a-SAH. METHODS: PA and SB were objectively measured at six months post a-SAH with an accelerometer-based activity monitor, with the aim to cover three consecutive weekdays. Total time spent in PA (comprising walking, cycling, running and non-cyclic movement) and SB (comprising sitting and lying) was determined. Also, in-depth analyses were performed to determine the accumulation and distribution of PA and SB throughout the day. Binary time series were created to determine the mean bout length and the fragmentation index. Measures of PA and SB in persons with a-SAH were compared to those in sex- and age-matched healthy controls. RESULTS: The 51 participants comprised 33 persons with a-SAH and 18 controls. None of the participants had signs of paresis or spasticity. Persons with a-SAH spent 105 min/24 h being physically active, which was 35 min/24 h less than healthy controls (p = 0.005). For PA, compared with healthy controls, the mean bout length was shorter in those with a-SAH (12.0 vs. 13.5 s, p = 0.006) and the fragmentation index was higher (0.053 vs. 0.041, p < 0.001). Total sedentary time during waking hours showed no significant difference between groups (514 min vs. 474 min, p = 0.291). For SB, the mean bout length was longer in persons with a-SAH (122.3 vs. 80.5 s, p = 0.024), whereas there was no difference in fragmentation index between groups (0.0032 vs 0.0036, p = 0.396). CONCLUSIONS: Persons with a-SAH are less physically active, they break PA time into shorter periods, and SB periods last longer compared to healthy controls. Since inactive lifestyles and prolonged uninterrupted periods of SB are independent risk factors for poor cardiovascular health, interventions seem necessary and should target both PA and SB. STUDY REGISTRATION: Dutch registry number: NTR 2085.

SMAD2 Mutations Are Associated with Arterial Aneurysms and Dissections.

We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF-ß signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF-ß signaling pathway exhibit arterial aneurysms and dissections as key features.

Hypopituitarism after subarachnoid haemorrhage, do we know enough?

BACKGROUND: Fatigue, slowness, apathy and decrease in level of activity are common long-term complaints after a subarachnoid haemorrhage (SAH). They resemble the symptoms frequently found in patients with endocrine dysfunction. Pituitary dysfunction may be the result of SAH or its complications. We therefore hypothesized that it may explain some of the long-term complaints after SAH. We reviewed the literature to clarify the occurrence, pattern and severity of endocrine abnormalities and we attempted to identify risk factors for hypopituitarism after SAH. We also assessed the effect of hypopituitarism on long-term functional recovery after SAH. METHODS: In a MEDLINE search for studies published between 1995 and 2014, we used the term subarachnoid haemorrhage in combination with pituitary, hypopituitarism, growth hormone, gonadotropin, testosterone, cortisol function, thyroid function and diabetes insipidus. We selected all case-series and cohort studies reporting endocrine function at least 3 months after SAH and studied their reported prevalence, pathogenesis, risk factors, clinical course and outcome. RESULTS: We identified 16 studies describing pituitary function in the long term after SAH. The reported prevalence of endocrine dysfunction varied from 0 to 55% and the affected pituitary axes differed between studies. Due to methodological issues no inferences on risk factors, course and outcome could be made. CONCLUSIONS: Neuroendocrine dysfunction may be an important and modifiable determinant of poor functional outcome after SAH. There is an urgent need for well-designed prospective studies to more precisely assess its incidence, clinical course and effect on mood, behaviour and quality of life.

Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial.

BACKGROUND: Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage. METHODS: We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome-defined as a score of 4-5 on the modified Rankin Scale-3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36). FINDINGS: 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85-1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86-1·08). INTERPRETATION: Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. FUNDING: Netherlands Heart Foundation, UK Medical Research Council.

Daily patterns of fatigue after subarachnoid haemorrhage: an ecological momentary assessment study.

OBJECTIVE: To examine the daily course of, and factors associated with, momentary fatigue after subarachnoid haemorrhage, and to explore subgroups of patients with distinct diurnal patterns of fatigue. DESIGN: Observational study using ecological momentary assessment. SUBJECTS: A total of 41 participants with subarachnoid haemorrhage. METHODS: Patients with fatigue were included within one year post-onset. Momentary fatigue (scale 1-7) was assessed with repeated measurements (10-11 times/day) during 7 consecutive days. Multilevel-mixed-model analyses and latent-class trajectory modelling were conducted. RESULTS: Mean (standard deviation; SD) age of the group was 53.9 (13.0) years, 56% female, and mean (SD) time post-subarachnoid haemorrhage onset was 9.3 (3.2) months. Mean (SD) momentary fatigue over all days was 3.22 (1.47). Fatigue increased significantly (p < 0.001) over the day, and experiencing more burden of fatigue and day type (working day vs weekend day) were significantly (p < 0.05) associated with higher momentary fatigue. Three subgroups could be distinguished based on diurnal patterns of fatigue. The largest group (n = 17, 41.5%) showed an increasing daily pattern of fatigue. CONCLUSION: Momentary fatigue in patients with subarachnoid haemorrhage increases over the day, and diurnal patterns of fatigue differ between  participants. In addition to conventional measures, momentary measures of fatigue might provide valuable information for physicians to optimize personalized management of fatigue after subarachnoid haemorrhage.

Fatigue is Associated with Reduced Participation and Health-Related Quality of Life Five Years After Perimesencephalic Subarachnoid Haemorrhage: A Multicentre Cross-Sectional Study.

OBJECTIVE: To determine whether fatigue is associated with participation and health-related quality of life 5 years after perimesencephalic subarachnoid haemorrhage. DESIGN: Multicentre cross-sectional study. SUBJECTS: Forty-six patients with perimesencephalic subarachnoid haemorrhage. METHODS: Fatigue was assessed with the Fatigue Severity Scale, participation (frequency, restrictions, satisfaction) with the Utrecht Scale for Evaluation of Rehabilitation-Participation, healthrelated quality of life with the Stroke-Specific Quality of Life Scale-12, symptoms of depression and anxiety with the Hospital Anxiety and Depression Scale, and coping with the Coping Inventory for Stressful Situations. RESULTS: A total of 46 patients were included (63% men, mean age 50.4 ± 9.4 years), with a mean time of 4.7 ± 1.6 years after perimesencephalic subarachnoid haemorrhage onset. Fatigued patients (33%) had worse participation (p < 0.01) and health-related quality of life (p < 0.001) than non-fatigued patients, and more often had hypertension, depression, anxiety and emotion-oriented coping (p < 0.05). Fatigue severity was inversely and independently (p < 0.005) associated with participation frequency (B = -3.62), satisfaction (B = -4.54), having restrictions (odds ratio = 2.48, 95% confidence interval 1.079-5.685), and health-related quality of life (B = -0.19), adjusted for depression, anxiety, and/or hypertension. CONCLUSION: Five years after perimesencephalic subarachnoid haemorrhage, one-third of patients still reported fatigue, which was associated with worse participation and health-related quality of life. Future studies should examine whether these patients may benefit from rehabilitation aimed at fatigue.

Neurovascular abnormalities in patients with Loeys-Dietz syndrome type III.

The aim of this article is to describe neurovascular findings in patients with Loeys Dietz syndrome type III and their possible clinical impact. Loeys Dietz syndrome type III, caused by pathogenic SMAD3 variants, is an autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. Neurovascular abnormalities have been described in other heritable aortic syndromes, however, reliable data in Loeys Dietz syndrome type III is missing. In our tertiary center, all adult patients with confirmed Loeys Dietz syndrome type III are followed in a standardized aorta outpatient clinic including Computed Tomography Angiography (CTA) of the head and neck region at baseline and (tri) yearly during follow-up. We performed an analysis of the neurovascular imaging findings and clinical follow-up. The primary outcome was a combined endpoint of mortality, dissection, cerebral vascular event and intervention. In addition, tortuosity and vascular growth were assessed. In total 26 patients (mean age 38.4 years, 38.5% males) underwent 102 (mean 3.9 (1-8) per patient) neurovascular Computed Tomography Angiography scans between 2010 and 2021. In 84.6% some form of neurovascular abnormality was found. The abnormalities at baseline were aneurysm (26.9%) dissection flap (7.7%), arterial tortuosity (61.5%), arterial coiling (23.1%) and arterial kinking (3.8%). During follow up (mean 8.85 (1-11) years) one patient suffered from sudden death and one patient needed a neuro-radiological intervention. No cerebral bleeding or stroke occurred. In conclusion, neurovascular imaging in Loeys Dietz syndrome type III patients revealed abnormalities such as aneurysm, tortuosity, coiling and kinking in the vast majority of patients, but clinical events were rare. Neurovascular screening and follow up is advised in all Loeys Dietz syndrome type III patients.

Fatigue in relation to long-term participation outcome in aneurysmal subarachnoid haemorrhage survivors.

OBJECTIVE: To examine the association of fatigue with long-term participation in aneurysmal subarachnoid haemorrhage survivors. DESIGN: Cohort study, 4 years post-onset. SUBJECTS: A total of 59 patients with aneurysmal subarachnoid haemorrhage. METHODS: Participation performance was assessed with the Sickness Impact Profile-68, participation autonomy and problem experience with the Impact on Participation and Autonomy questionnaire, and community integration with the Community Integration Questionnaire. Fatigue was assessed with the Fatigue Severity Scale and depression with the Center for Epidemiologic Studies-Depression scale. Multivariable linear regression analyses were performed. RESULTS: Fifty-nine survivors (mean age 53.0 years, standard deviation (SD) 10.8 years) were included, of which 59.3% was fatigued. Fatigued patients had significantly worse participation scores than non-fatigued patients regarding performance (p < 0.001), autonomy indoors (p = 0.001), autonomy outdoors (p = 0.002) and problem experience (p = 0.001), but not regarding community integration. More severe fatigue was related to worse participation in terms of performance (B = 2.79, p < 0.001) and problem experience (B = 0.08, p = 0.003), adjusted for depression and inpatient rehabilitation. CONCLUSION: Four years after onset, many survivors of aneurysmal subarachnoid haemorrhage have persistent fatigue, which is independently associated with reduced participation in activities of daily living. Therefore, future studies should investigate whether rehabilitation programs that focus on fatigue are effective in improving long-term participation outcome after aneurysmal subarachnoid haemorrhage.

Withdrawal of statins and risk of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. METHODS: We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. RESULTS: During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). CONCLUSIONS: Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.

Shifting Carotid Web Due to a Wandering and Rotating Carotid Artery.

This case report describes the finding of a carotid web in combination with a wandering and rotating carotid artery, resulting in a stroke.

Fatigue After Aneurysmal Subarachnoid Hemorrhage Is Highly Prevalent in the First-Year Postonset and Related to Low Physical Fitness: A Longitudinal Study.

OBJECTIVE: The aim of the study was to investigate whether low physical fitness and inactive and sedentary lifestyles play a role in the severity of fatigue in patients with aneurysmal subarachnoid hemorrhage (a-SAH). DESIGN: This is a prospective 1-yr follow-up study, including a total of 52 patients with a-SAH. Outcome measures included the Fatigue Severity Scale score, peak oxygen uptake (VO2peak), isokinetic knee muscle strength (peak torque), physical activity (% 24-hr period), and sedentary behavior (% waking hours) and were evaluated at 6 and 12 mos after onset. RESULTS: Fatigue was highly prevalent in the first year and reported by 48% of the patients at 6 mos and by 52% at 12 mos after a-SAH. Fatigue was associated with the knee extension (P < 0.001) and flexion strength (P < 0.001). A nonsignificant trend for a relationship was found between fatigue and the aerobic capacity (P = 0.079). No relationships were found between fatigue and physical activity or sedentary behavior. Fatigue could not be predicted by disease-related characteristics. CONCLUSIONS: Half of the patients were fatigued in the first year after a-SAH. Interventions are necessary to reduce fatigue and should consider exercise training as a potential contributor to a multimodal treatment, preventing debilitating conditions after a-SAH. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Recognize the association between fatigue and physical fitness in patients after aneurysmal subarachnoid hemorrhage; (2) Determine the severity of fatigue complaints in patient after aneurysmal subarachnoid hemorrhage; and (3) Discuss the role of physical deconditioning in the management of fatigue in patients after aneurysmal subarachnoid hemorrhage. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

People With Aneurysmal Subarachnoid Hemorrhage Have Low Physical Fitness and Can Be Predisposed to Inactive and Sedentary Lifestyles.

BACKGROUND: Physical inactivity, sedentary lifestyles, and low functional outcome are thought to impact the level of physical fitness in patients with aneurysmal subarachnoid hemorrhage (a-SAH). However, changes in fitness over time and associated factors have not been studied in a-SAH. OBJECTIVE: The objective was to evaluate the level of physical fitness in the first year after a-SAH and explore longitudinal relations with physical activity, sedentary behavior, and functional outcome. Additionally, we evaluated whether physical fitness could be predicted by disease-related characteristics (ie, severity of a-SAH, location of the aneurysm, treatment procedure, pituitary dysfunction, and complications). DESIGN: This was a prospective 1-year follow-up study. METHODS: Fifty-two participants performed exercise testing at 6 and 12 months after a-SAH. Cardiopulmonary exercise testing and isokinetic dynamometry were applied to determine the peak oxygen uptake $({\rm{\dot{V}}}{{\rm{o}}_{2{\rm{peak}}}})$ and the peak torque of the knee extensors (PText) and flexors (PTflex). In addition, physical activity and sedentary behavior were evaluated by accelerometer-based activity monitoring. The functional outcome was assessed by the Functional Independence Measure and Functional Assessment Measure. Disease-related characteristics were collected at hospital intake. RESULTS: At both 6 and 12 months, all fitness parameters were lower compared with predicted values (ranging from 18% to 28%). Physical activity is related to both ${\rm{\dot{V}}}{{\rm{o}}_{{\rm{2peak}}}}$ and PTflex. The Functional Independence Measure and Functional Assessment Measure scores was related to PText and PTflex. Further, participants who underwent surgical clipping had lower ${\rm{\dot{V}}}{{\rm{o}}_{{\rm{2peak}}}}$ and PTflex. LIMITATIONS: Longitudinal observations cannot confirm causality. CONCLUSIONS: Levels of physical fitness remain low over the first year after a-SAH. Participants who were physically more active had higher levels of physical fitness, whereas participants with impaired functional outcome or who were treated with surgical clipping were at risk of low physical fitness. Exercise interventions are warranted and should focus on the promotion of physical activity and target patients with impaired functional outcome or those who have been treated with surgical clipping.

Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the more frequent pathologic entities in daily neurosurgical practice. Historically, CSDH was considered progressive recurrent bleeding with a traumatic cause. However, recent evidence has suggested a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds, and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH to direct further research questions aiming to optimize treatment for the individual patient. METHODS: We performed a thorough literature search in PubMed, Ovid, EMBASE, CINAHL, and Google scholar, focusing on any aspect of the pathophysiology and nonsurgical treatment of CSDH. RESULTS: After a (minor) traumatic event, the dural border cell layer tears, which leads to the extravasation of cerebrospinal fluid and blood in the subdural space. A cascade of inflammation, impaired coagulation, fibrinolysis, and angiogenesis is set in motion. The most commonly used treatment is surgical drainage. However, because of the pathophysiologic mechanisms, the mortality and high morbidity associated with surgical drainage, drug therapy (dexamethasone, atorvastatin, tranexamic acid, or angiotensin-converting enzyme inhibitors) might be a beneficial alternative in many patients with CSDH. CONCLUSIONS: Based on pathophysiologic mechanisms, animal experiments, and small patient studies, medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the nonsurgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess which treatment is most effective in each individual patient.

Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurological disease with a rapidly rising incidence due to increasing age and widespread use of anticoagulants. Surgical intervention by burr-hole craniotomy (BHC) is the current standard practice for symptomatic patients, but associated with complications, a recurrence rate of up to 30% and increased mortality. Dexamethasone (DXM) therapy is, therefore, used as a non-surgical alternative but considered to achieve a lower success rate. Furthermore, the benefit of DXM therapy appears much more deliberate than the immediate relief from BHC. Lack of evidence and clinical equipoise among caregivers prompts the need for a head-to-head randomised controlled trial. The objective of this study is to compare the effect of primary DXM therapy versus primary BHC on functional outcome and cost-effectiveness in symptomatic patients with CSDH. METHODS/DESIGN: This study is a prospective, multicentre, randomised controlled trial (RCT). Consecutive patients with a CSDH with a Markwalder Grading Scale (MGS) grade 1 to 3 will be randomised to treatment with DXM or BHC. The DXM treatment scheme will be 16 mg DXM per day (8 mg twice daily, days 1 to 4) which is then halved every 3 days until a dosage of 0.5 mg a day on day 19 and stopped on day 20. If the treatment response is insufficient (i.e. persistent or progressive symptomatology due to insufficient haematoma resolution), additional surgery can be performed. The primary outcomes are the functional outcome by means of the modified Rankin Scale (mRS) score at 3 months and cost-effectiveness at 12 months. Secondary outcomes are quality of life at 3 and 12 months using the Short Form Health Survey (SF-36) and Quality of Life after Brain Injury Overall Scale (QOLIBRI), haematoma thickness after 2 weeks on follow-up computed tomography (CT), haematoma recurrence during the first 12 months, complications and drug-related adverse events, failure of therapy within 12 months after randomisation and requiring intervention, mortality during the first 3 and 12 months, duration of hospital stay and overall healthcare and productivity costs. To test non-inferiority of DXM therapy compared to BHC, 210 patients in each treatment arm are required (assumed adjusted common odds ratio DXM compared to BHC 1.15, limit for inferiority < 0.9). The aim is to include a total of 420 patients in 3 years with an enrolment rate of 60%. DISCUSSION: The present study should demonstrate whether treatment with DXM is as effective as BHC on functional outcome, at lower costs. TRIAL REGISTRATION: EUCTR 2015-001563-39 . Date of registration: 29 March 2015.

Long-term fatigue after perimesencephalic subarachnoid haemorrhage in relation to cognitive functioning, mood and comorbidity.

PURPOSE: To study relationships between fatigue and objective and subjective cognitive functioning, mood and comorbidity in the long term after perimesencephalic subarachnoid haemorrhage (PM-SAH). METHODS: Cross-sectional study. Objective cognitive functioning was measured with: Trail Making Test; Symbol Substitution; D2; Verbal and Semantic Fluency; Tower Test; Digit Span; 15-Words Test; Rey Complex Figure. Subjective cognitive functioning: Cognitive Failure Questionnaire. Fatigue: Fatigue Severity Scale. Mood: Hospital Anxiety and Depression Scale. RESULTS: Forty-six patients, mean age 50.4 (SD = 9.4), mean time after PM-SAH 4.7 (SD = 1.6) years participated. Patients with fatigue (33%) had significantly lower scores than patients without fatigue on most objective cognitive functioning tests (p < 0.05). Fatigue score was significantly associated with subjective and objective cognitive functioning, mood and comorbidity. After adjustment for mood and comorbidity, fatigue remained associated with attention and executive functioning. CONCLUSIONS: This study supports our previous findings that a third of patients with PM-SAH experience fatigue and problems of cognitive functioning, also in the long term. Future research should investigate whether these patients would benefit from long-term follow-up and/or cognitive rehabilitation programmes. Implications for Rehabilitation Consequences for patients with PM-SAH are underestimated. One in every three patients suffered from fatigue in the long term after onset of PM-SAH. Patients with PM-SAH should be screened for problems of cognitive functioning, fatigue and mood in outpatient clinic just as patients with aneurysmal SAH.

The six-minute walk test predicts cardiorespiratory fitness in individuals with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Peak oxygen uptake (VO2peak) established during progressive cardiopulmonary exercise testing (CPET) is the "gold-standard" for cardiorespiratory fitness. However, CPET measurements may be limited in patients with aneurysmal subarachnoid hemorrhage (a-SAH) by disease-related complaints, such as cardiovascular health-risks or anxiety. Furthermore, CPET with gas-exchange analyses require specialized knowledge and infrastructure with limited availability in most rehabilitation facilities. OBJECTIVES: To determine whether an easy-to-administer six-minute walk test (6MWT) is a valid clinical alternative to progressive CPET in order to predict VO2peak in individuals with a-SAH. METHODS: Twenty-seven patients performed the 6MWT and CPET with gas-exchange analyses on a cycle ergometer. Univariate and multivariate regression models were made to investigate the predictability of VO2peak from the six-minute walk distance (6MWD). RESULTS: Univariate regression showed that the 6MWD was strongly related to VO2peak (r = 0.75, p < 0.001), with an explained variance of 56% and a prediction error of 4.12 ml/kg/min, representing 18% of mean VO2peak. Adding age and sex to an extended multivariate regression model improved this relationship (r = 0.82, p < 0.001), with an explained variance of 67% and a prediction error of 3.67 ml/kg/min corresponding to 16% of mean VO2peak. CONCLUSIONS: The 6MWT is an easy-to-administer submaximal exercise test that can be selected to estimate cardiorespiratory fitness at an aggregated level, in groups of patients with a-SAH, which may help to evaluate interventions in a clinical or research setting. However, the relatively large prediction error does not allow for an accurate prediction in individual patients.

Impaired muscle strength may contribute to fatigue in patients with aneurysmal subarachnoid hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (a-SAH) show long-term fatigue and face difficulties in resuming daily physical activities. Impaired muscle strength, especially of the lower extremity, impacts the performance of daily activities and may trigger the onset of fatigue complaints. The present study evaluated knee muscle strength and fatigue in patients with a-SAH. This study included 33 patients, 6 months after a-SAH, and 33 sex-matched and age-matched healthy controls. Isokinetic muscle strength of the knee extensors and flexors was measured at 60 and 180°/s. Maximal voluntary muscle strength was defined as peak torque and measured in Newton-meter. Fatigue was examined using the Fatigue Severity Scale. In patients with a-SAH, the maximal knee extension was 22% (60°/s) and 25% (180°/s) lower and maximal knee flexion was 33% (60°/s) and 36% (180°/s) lower compared with that of matched controls (P≤0.001). The Fatigue Severity Scale score was related to maximal knee extension (60°/s: r=-0.426, P=0.015; 180°/s: r=-0.376, P=0.034) and flexion (60°/s: r=-0.482, P=0.005; 180°/s: r=-0.344, P=0.083). The knee muscle strength was 28-47% lower in fatigued (n=13) and 11-32% lower in nonfatigued (n=20) patients; deficits were larger in fatigued patients (P<0.05), particularly when the muscle strength (peak torque) was measured at 60°/s. The present results indicate that patients with a-SAH have considerably impaired knee muscle strength, which is related to more severe fatigue. The present findings are exploratory, but showed that knee muscle strength may play a role in the severity of fatigue complaints, or vice versa. Interventions targeting fatigue after a-SAH seem necessary and may consider strengthening exercise training in order to treat a debilitating condition.