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.).

Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study.

BACKGROUND: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI. METHODS: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4-6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses. RESULTS: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17-2.27) and at day 5 after DCI 1.04 (95% CI 0.84-1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results. CONCLUSIONS: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3-/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI.

The cognitive status of chronic subdural hematoma patients after treatment: an exploratory study.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and longer term aspects of the cognitive status of CSDH patients are unknown. In this study, we aim to explore the cognitive status of CSDH patients after treatment. METHODS: An exploratory study in which CSDH patients were assessed 3 months after treatment and compared to healthy controls. A total of 56 CSDH patients (age 72.1 SD ± 10.8 years with 43 [77%] males) and 60 healthy controls were included (age 67.5 ± SD 4.8 with 34 [57%] males). Cognitive testing was performed using the Telephonic Interview of Cognitive Status-modified (TICS-m), a 12-item questionnaire in which a total of 50 points can be obtained on several cognitive domains. RESULTS: Median time between treatment and cognitive testing was 93 days (range 76-139). TICS-m scores of CSDH patients were significantly lower than healthy controls, after adjusting for age and sex: mean score 34.6 (95% CI: 33.6-35.9) vs. 39.6 (95% CI: 38.5-40.7), p value < 0.001. More than half (54%) of CSDH patients have cognitive scores at follow-up that correspond with cognitive impairment. CONCLUSION: A large number of CSDH patients show significantly worse cognitive status 3 months after treatment compared to healthy controls. This finding underlines the importance of increased awareness for impaired cognition after CSDH. Further research on this topic is warranted.

Biomarker S100B in plasma a screening tool for mild traumatic brain injury in an emergency department.

INTRODUCTION: A computerized tomography (CT) scan is an effective test for detecting traumatic intracranial findings after mild traumatic brain injury (mTBI). However, a head CT is costly, and can only be performed in a hospital. OBJECTIVE: To determine if the addition of plasma S100B to clinical guidelines could lead to a more selective scanning strategy without compromising safety. METHODS: We conducted a single center prospective cohort study at the emergency department. Patients (≥16 years) who received head CT and had a blood draw were included. The primary outcome was the accuracy of plasma S100B to predict the presence of any traumatic intracranial lesion on head CT. RESULTS: We included 495 patients, out of the 74 patients who had traumatic intracranial lesions, 5 patients had a plasma S100B level below the cutoff value of 0.105 ug/L. For the detection of traumatic intracranial injury, S100B had a sensitivity of 0.932 , a specificity of 0.157, a negative predictive value of 0.930, and a positive predictive value of 0.163. CONCLUSIONS: Among patients undergoing guideline-based CT scan for mTBI, the use of S100B, would results in a further decrease (14.8%) of CT scans but at a cost of missed injury, without clinical consequence, on CT.

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months. METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812. FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups. INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. FUNDING: Fonds NutsOhra.

Presenting symptoms and functional outcome of chronic subdural hematoma patients.

BACKGROUND: Patients with chronic subdural hematoma (CSDH) can present with a variety of signs and symptoms. The relationship of these signs and symptoms with functional outcome is unknown. Knowledge of these associations might aid clinicians in the choice to initiate treatment and may allow them to better inform patients on expected outcomes. OBJECTIVE: To investigate if presenting signs and symptoms influence functional outcome in patients with CSDH. METHODS: We conducted a retrospective analysis of consecutive CSDH patients in three hospitals. Glasgow Outcome Scale Extended (GOS-E) scores were obtained from the first follow-up visit after treatment. An ordinal multivariable regression analysis was performed, to assess the relationship between the different signs and symptoms on the one hand and functional outcome on the other adjusted for potential confounders. RESULTS: We included 1,307 patients, of whom 958 (73%) were male and mean age was 74 (SD ± 11) years. Cognitive complaints were associated with lower GOS-E scores at follow-up (aOR 0.7, 95% CI: 0.5 - 0.8) Headache and higher Glasgow Coma Scale (GCS) scores were associated with higher GOS-E scores. (aOR 1.9, 95% CI: 1.5-2.3 and aOR 1.3, 95% CI: 1.2-1.4). CONCLUSION: Cognitive complaints are independently associated with worse functional outcome, whereas headache and higher GCS scores are associated with better outcome. The increased probability of unfavorable outcome in patients with CSDH who present with cognitive complaints favors a more prominent place of assessing cognitive status at diagnosis.

Pathophysiology of transient neurological deficit in patients with chronic subdural hematoma: A systematic review.

Patients with chronic subdural hematoma (CSDH) can have transient neurological deficits deficit (TND) mimicking transient ischemic attacks. The prevalence of TNDs in CSDH varies between 1%-24%, depending on TND definition. Despite this high prevalence the pathophysiology of TND in CSDH is not clear in many cases. In this systematic review, we aim to unravel the responsible mechanism. Pubmed and Embase were searched for all articles concerning the pathophysiology of TND as a presenting symptom in patients with CSDH. There were no publication date restrictions for the articles in the search. Two reviewers independently selected studies for inclusion and subsequently extracted the necessary data. Out of 316 identified references, 15 met the inclusion criteria. Several articles mentioned multiple pathophysiological mechanisms. One of the proposed etiologies of TND was epileptic activity, stated by three articles. In contrast, three different studies stated that seizures are unlikely to cause TND. Five papers suggested that obstruction of blood flow, caused by the hematoma or subsequent swelling, might be the cause. Six articles made no definite statement on the responsible pathophysiological mechanism of TND. Different mechanisms have been proposed to be the cause of TNDs in patients with CSDH. Based on this review, the exact pathophysiology of TND remains unclear. We suggest that future studies on this topic should incorporate MRI of the brain (with diffusion-weighted imaging) and EEG, to provide better insight into TND pathophysiology. The knowledge resulting from future studies might contribute to better understanding of TND and optimal treatment in CSDH.

Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study.

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.

Mortality after chronic subdural hematoma is associated with frailty.

PURPOSE: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality. METHODS: A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed. RESULTS: A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD ± 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0-213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2-1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0-1.7), inability to live independently (HR 1.4, 95% CI: 1.1-1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1-1.9), and number of medications used (HR 1.0; 95% CI: 1.0-1.1) were independently associated with mortality. CONCLUSIONS: CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted.

External validation of prognostic models predicting outcome after chronic subdural hematoma.

BACKGROUND: Several prognostic models for outcomes after chronic subdural hematoma (CSDH) treatment have been published in recent years. However, these models are not sufficiently validated for use in daily clinical practice. We aimed to assess the performance of existing prediction models for outcomes in patients diagnosed with CSDH. METHODS: We systematically searched relevant literature databases up to February 2021 to identify prognostic models for outcome prediction in patients diagnosed with CSDH. For the external validation of prognostic models, we used a retrospective database, containing data of 2384 patients from three Dutch regions. Prognostic models were included if they predicted either mortality, hematoma recurrence, functional outcome, or quality of life. Models were excluded when predictors were absent in our database or available for < 150 patients in our database. We assessed calibration, and discrimination (quantified by the concordance index C) of the included prognostic models in our retrospective database. RESULTS: We identified 1680 original publications of which 1656 were excluded based on title or abstract, mostly because they did not concern CSDH or did not define a prognostic model. Out of 18 identified models, three could be externally validated in our retrospective database: a model for 30-day mortality in 1656 patients, a model for 2 months, and another for 3-month hematoma recurrence both in 1733 patients. The models overestimated the proportion of patients with these outcomes by 11% (15% predicted vs. 4% observed), 1% (10% vs. 9%), and 2% (11% vs. 9%), respectively. Their discriminative ability was poor to modest (C of 0.70 [0.63-0.77]; 0.46 [0.35-0.56]; 0.59 [0.51-0.66], respectively). CONCLUSIONS: None of the examined models showed good predictive performance for outcomes after CSDH treatment in our dataset. This study confirms the difficulty in predicting outcomes after CSDH and emphasizes the heterogeneity of CSDH patients. The importance of developing high-quality models by using unified predictors and relevant outcome measures and appropriate modeling strategies is warranted.

Radiological prognostic factors of chronic subdural hematoma recurrence: a systematic review and meta-analysis.

PURPOSE: Chronic subdural hematoma (CSDH) is associated with high recurrence rates. Radiographic prognostic factors may identify patients who are prone for recurrence and who might benefit further optimization of therapy. In this meta-analysis, we systematically evaluated pre-operative radiological prognostic factors of recurrence after surgery. METHODS: Electronic databases were searched until September 2020 for relevant publications. Studies reporting on CSDH recurrence in symptomatic CSDH patients with only surgical treatment were included. Random or fixed effects meta-analysis was used depending on statistical heterogeneity. RESULTS: Twenty-two studies were identified with a total of 5566 patients (mean age 69 years) with recurrence occurring in 801 patients (14.4%). Hyperdense components (hyperdense homogeneous and mixed density) were the strongest prognostic factor of recurrence (pooled RR 2.83, 95% CI 1.69-4.73). Laminar and separated architecture types also revealed higher recurrence rates (RR 1.37, 95% CI 1.04-1.80 and RR 1.76 95% CI 1.38-2.16, respectively). Hematoma thickness and midline shift above predefined cut-off values (10 mm and 20 mm) were associated with an increased recurrence rate (RR 1.79, 95% CI 1.45-2.21 and RR 1.38, 95% CI 1.11-1.73, respectively). Bilateral CSDH was also associated with an increased recurrence risk (RR 1.34, 95% CI 0.98-1.84). LIMITATIONS: Limitations were no adjustments for confounders and variable data heterogeneity. Clinical factors could also be predictive of recurrence but are beyond the scope of this study. CONCLUSIONS: Hyperdense hematoma components were the strongest prognostic factor of recurrence after surgery. Awareness of these findings allows for individual risk assessment and might prompt clinicians to tailor treatment measures.

Traumatic Brain Injury in Patients Receiving Direct Oral Anticoagulants.

BACKGROUND: Emergency departments (EDs) are faced with a growing number of patients with traumatic brain injury (TBI) using direct oral anticoagulants (DOACs). However, there remains uncertainty about the bleeding risk, rate of hematoma expansion, and the efficacy of reversal strategies in these patients. OBJECTIVE: This study aims to identify the risk of traumatic hemorrhagic complications in patients with TBI using DOACs. METHODS: In this retrospective study we included patients with TBI. All TBI patients were using DOACs, attended one of the three EDs of our hospital between January 2016 and October 2019, and received a computed tomography (CT) scan of the brain. The primary outcome was any traumatic intracranial hemorrhage on CT. Secondary outcomes were the use of reversal agents, secondary neurological deterioration, a neurosurgical intervention within 30 days after the injury, length of stay (LOS), Glasgow Outcome Scale (GOS) at discharge, and mortality. RESULTS: Of the included patients (N = 316), 24 patients (7.6%, 95% confidence interval [CI] 4.2-9.8) presented with a traumatic intracranial hematoma (ICH). Seven patients (2.2%, 95% CI 0.6-3.8) received a reversal agent and 1 patient (0.3%, 95% CI -0.3-0.9) underwent a neurosurgical intervention. Of the 24 patients with a traumatic ICH, progression of the lesion was seen in 6 patients (1.9%, 95% CI 0.4-3.4). The mean LOS was 6.5 days (95% CI 3.0-10.1) and the mean GOS at discharge was 4 (95% CI 3.6-4.6). Death occurred in 1 patient (0.3%, 95% CI -0.3-0.9) suffering from an ICH. CONCLUSION: Based on the present findings it can be postulated that TBI patients using DOACs have a low risk for ICH. Hematoma progression occurred, however, in a substantial number of patients. Considering the retrospective nature of the present study, future prospective trials are needed to confirm this finding.

Activities and Participation in the First 6 Months After Mild Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the natural course of activities and participation of children up to 6 months after a mild traumatic brain injury (mTBI). METHODS: A prospective longitudinal cohort study with complete data sets of 231 children diagnosed with mTBI and their caregivers. MAIN MEASURES: Activities and participation assessed with the Child and Adolescent Scale of Participation (CASP) and the Children's Assessment of Participation and Enjoyment (CAPE) measured at 2 weeks, 3 months, and 6 months post-mTBI. Because of a ceiling effect, the primary outcome measure (CASP) was divided into deviant (not maximum score) or full functioning. RESULTS: Friedman's, Cochran's Q, and McNemar's tests (CASP) and repeated-measures analyses of variance (CAPE) showed significant increases in activities and participation between 2 weeks and 3 and 6 months after mTBI. Based on the parents' perspective, 67% of the children returned to full functioning at 6 months postinjury, with only 38% of the children describing themselves as functioning at their premorbid level. DISCUSSION: Findings indicate that most children return to maximum level of activities and participation over time after mTBI. In a substantial number of children, however, the level of activities and participation at 6 months postinjury is evaluated as lower than that of peers. The importance of investigating predictors for child and caregiver perspectives is emphasized.

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.

Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: the DIAGRAM prediction score.

OBJECTIVE: A substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH. METHODS: The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%). RESULTS: Independent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51-70 years with deep ICH and SVD, to more than 50% in patients aged 18-50 years with lobar or posterior fossa ICH without SVD. CONCLUSION: The DIAGRAM scores help to predict the probability of a macrovascular cause in patients with non-traumatic ICH based on age, ICH location, SVD and CTA.

Sleep-Related Leg Movements in Patients with Transient Ischemic Attack and Controls.

BACKGROUND: Periodic leg movements during sleep (PLMS) have been associated with an increased risk for cardiovascular diseases and there is a high prevalence of PLMS found in patients with obstructive sleep apnea syndrome (OSAS). We evaluated patients with transient ischemic attack (TIA) for PLMS and respiratory related leg movements (RRLM), versus a control group without TIA. METHODS: Twenty-five patients with TIA and 34 patients with no vascular diagnosis were referred for polysomnography. Diagnosis of PLMS was made if the periodic leg movement index (PLMI) was ≥5 and clinical significant as PLMI ≥15. RESULTS: There was no significant difference in PLMI ≥5 and ≥15 between patients with and without TIA. In the absence of OSAS, 2 out of 5 TIA patients (40%) had a PLMI ≥15 compared to 1 of the 19 patients without TIA (5%; p = 0.037). There was no increase in RRLMs when OSAS was present. CONCLUSIONS: TIA patients did not have higher PLMI compared to controls, and in the presence of OSAS, there was no increase in RRLMs compared to patients without TIA. In selective patients, PLMS could be associated with cardiovascular diseases, since PLMS was clinically more often found in the TIA group without OSAS.

Yield of Computed Tomography (CT) Angiography in Patients with Acute Headache, Normal Neurological Examination, and Normal Non Contrast CT: A Meta-Analysis.

BACKGROUND: Patients with acute severe headache, normal neurological examination, and a normal noncontrast head computed tomography (NCCT) may still have subarachnoid hemorrhage, cerebral venous thrombosis (CVT), cervical arterial dissection, or reversible cerebral vasoconstriction syndrome (RCVS). Computed tomography angiography (CTA) is used increasingly in the emergency department for evaluating this, but its added value remains controversial. METHODS: We retrospectively collected data on the diagnostic yield of CTA in patients with acute severe headache, normal neurological examination, and normal NCCT who received additional CTA in the acute phase in 2 secondary referral centers for vascular neurology. We combined data of our patients with those from the literature and performed a meta-analysis. RESULTS: We included 88 patients from our hospital files and 641 patients after literature search. Of 729 patients 54 had a vascular abnormality on CTA (7.4%; 95% confidence interval [CI] 5.5%-9.3%). Abnormalities consisted of aneurysms (n = 42; 5.4%; 95% CI 3.8%-7.0%), CVT (n = 3, .5%), RCVS (n = 4, .5%), Moyamoya syndrome (n = 2, .3%), arterial dissection (n = 2, .3%), and ischemia (n = 1, .1%). Because most of the aneurysms were probably incidental findings, only 12 (1.6%) patients had a clear relation between the headache and CTA findings. The number needed to scan to find an abnormality was 14 overall, and 61 for an abnormality other than an aneurysm. CONCLUSION: Diagnostic yield of CTA in patients with acute headache, normal neurological examination, and normal NCCT is low, but because of the possible therapeutic consequences, its use might be justified in the emergency setting. Prospective studies confirming these results including cost-effectiveness analyses are needed.

Fixed Versus Variable Dosing of Prothrombin Complex Concentrate in Vitamin K Antagonist-Related Intracranial Hemorrhage: A Retrospective Analysis.

BACKGROUND: Millions of patients receive vitamin K antagonist (VKA) therapy worldwide. Annually 0.2-1 % of all VKA users develops an intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is administered to restore the INR ≤ 1.5 in an attempt to limit hematoma growth. In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH. METHODS: In a before and after design, we compared successful achievement of an INR ≤ 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of VKA. Data of the two cohorts of patients were retrospectively collected from medical records. RESULTS: A median dosage of 1750 IU was given per patient in the variable dose group (n = 25) versus 1000 IU in the fixed dose group (n = 28). In the intention-to-treat analysis, 96 % achieved an INR ≤ 1.5 after an initial dose in the variable dose cohort compared to 68 % in the fixed dose cohort (p = 0.01). An additional dose was given in 2 (8 %) versus 9 (32 %) patients, respectively (p = 0.04). The median door-to-PCC-order time was 42 versus 32 min (p = 0.37) and the door-to-needle time was 81, respectively 60 min (p = 0.42). CONCLUSION: The fixed dose protocol necessitates additional PCC infusions more frequently to achieve a target INR ≤ 1.5. Door-to-order and door-to-needle time were shorter but, in this small cohort, not significantly so. The effect on clinical outcome remains unknown.