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Background And Aims

Neuropsychiatric symptoms (NPS) are prominent features of cognitive decline, but they have been understudied in patients with intracerebral hemorrhage (ICH). We aimed to assess prevalence and profiles of NPS and to evaluate their use in predicting long-term outcomes after ICH.

Methods

We analyzed data from consecutive ICH survivors enrolled in the “Prognosis of Intra-Cerebral Hemorrhage” (PITCH) study. Neuropsychiatric evaluation was performed 6 months after ICH using the validated Neuropsychiatric Inventory Questionnaire (NPI-Q).

Results

Out of 202 patients included in the study, 112 (55%) had at least one NPS after ICH. NPS were more common in patients diagnosed with dementia (75%). Affective symptoms were globally the most common neuropsychiatric feature, followed by vegetative symptoms and hyperactivity (present respectively in 38%, 26% and 23% of the cohort). Apathy and hyperactivity were associated with presence of dementia and cerebral amyloid angiopathy (CAA) MRI profile (all p < 0.05). Presence of NPS was independently associated to higher long-term mortality risk (hazard ratio [HR] 1.57; 95% confidence interval [95%CI] 1.0-2.5). Only a specific NPS profile (apathy and hyperactivity prevailing over affect) was associated with higher risk of developing dementia (HR 5.4; 95%CI 2.3-12.8).

Conclusions

NPS were present in more than half of ICH survivors during follow-up, with higher prevalence and severity in patients with dementia. We described distinctive patterns of NPS according to cognitive status, ICH localization, and predominant small vessel disease (CAA vs non-CAA) type. Presence and profile of NPS can inform on long-term mortality and dementia risk.

Background And Aims

To assess uptake and workflow metrics of hyperacute management in patients with non-traumatic intracerebral haemorrhage (ICH) in the emergency department (ED) and whether metrics are time-dependent.

Methods

Single center study of consecutive patients with ICH. We assessed workflow metrics and outcome comparing performance in patients arriving early(≤6 hours) compared to those arriving late(>6hours) after symptom onset.

Results

We enrolled 378 patients (age 74,IQR63-82, 51%female, NIHSS10,IQR 3-18 and GCS14,IQR10-15). The median onset-to-admission-time was 279minutes (IQR112-696), 220 patients(58%) arrived <6hours from onset, the median door-to-imaging-time was 25minutes (IQR17-47) and the median lengths-of-stay in the ED was 139minutes (IQR 83-220).

On admission, 84 patients(22%) were on anticoagulant therapy (27Vitamin-K antagonist with INR>1.3, 57direct oral anticoagulants) of whom 59 patients(70%) received prothrombin complex concentrate (door-to-treatment-time: 62minutes IQR 40-124minutes). Systolic blood pressure was >150mmHg in 257 patients (65%,median 177mmHg,IQR165-198) of whom 157 patients(64%) received any intravenous antihypertensive drugs in the ED (94% uradipil, median door-to-treatment-time: 39minutes IQR18-78 minutes). 46 patients (12%) received any immediate neurosurgical interventions (EVD or haematoma evacuation) before transfer to IMC/ICU.

There was no difference in any of these workflow metrics between patients arriving early or late except for longer door-to-imaging time (early: 23minutes,IQR17-35 vs. late 32minutes,IQR19-87, p<0.001). Seventy-two of 286 patients(25%) were functionally independent (mRS 0-2) at 3 months but no single workflow metric or specific intervention was independently associated with improved odds.

Conclusions

Delivery of medical therapies in the ED seems fast regardless of early/late arrival but uptake of specific treatments may further improve. Only 1 of 10 patients receives immediate neurosurgical intervention.

Trial Registration Number

not applicable

Background And Aims

Spontaneous intracerebral haemorrhage (ICH) is a feared complication of antithrombotic treatment, particularly with oral anticoagulants (OACs), due to high case fatality and disability. Previous studies produced equivocal results as to whether the prognosis of OAC-associated ICH differs by type of OAC.

Methods

Using Danish nationwide registries, we conducted a case-control study of all patients with first-ever ICH in 2005-2018 (n=16,765) matched by age, sex, and calendar year with general population controls. Main exposure was use of a vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC). We classified patients who died within 30 days of ICH onset as cases of fatal ICH. Conditional logistic regression models estimated adjusted odds ratios (aORs) [95% confidence intervals] for the association of anticoagulant drugs with ICH. The reference group was non-use of any antithrombotics in the previous year.

Results

The overall association with ICH was strongest for VKA (aOR 2.76 [2.57-2.96); for DOACs, aOR was 1.83 [1.61-2.07]. Corresponding values for fatal ICH were 4.41 [3.94-4.94] for VKA and 2.62 [2.09-3.29] for DOACs. For non-fatal ICH, associations were weaker: VKA 2.18 [2.00-2.38] and DOAC 1.59 [1.37-1.86]. Among VKA current users, the 30-day case fatality of ICH was 44.5% [42.3-46.7] and 35.6% [31.5-39.9] among DOAC current users.

Conclusions

Our results indicate that in an unselected Danish population, OAC use was associated with risk of ICH and to a greater extent with fatal ICH. VKA carried a greater case fatality of ICH than DOACs.

Trial Registration Number

Not applicable

Group Name

On behalf of the Dutch ICH Surgery Trial pilot study group, part of the CONTRAST consortium

Background And Aims

Previous randomized controlled trials could not demonstrate that diminishing intracerebral haemorrhage (ICH) volume by surgery improves functional outcome. Increasing evidence suggests that minimally-invasive surgery may be beneficial, in particular when performed early after symptom onset.

Methods

Prospective study with blinded outcome assessment of forty patients with ICH of at least 10mL from three participating centres, who received minimally-invasive endoscopy-guided surgery with the Artemis®-device within 8 hours of symptom onset. Primary safety outcome was the combination of death or increase in NIHSS ≥4 points at 24 hours. Primary technical effectiveness outcome was the percentage ICH-volume reduction at 24 hours.

Results

Mean age was 59 years (SD 14), median NIHSS 19 (IQR 13;22) and median ICH-volume 47.7mL (IQR 29;72) with a non-lobar location in 29 (73%). Nineteen patients (48%) had additional intraventricular haemorrhage. One patient used oral anticoagulation and 11 used antiplatelet therapy (28%). Median time from onset to surgery was 6,7 hours (IQR 5.4; 7.9). A primary safety outcome occurred in six patients, of whom one died; deterioration occurred before surgery in two. Three other patients (7.5%) died within 30 days. Median ICH volume reduction at 24 hours was 78% (IQR 50;89). Median postoperative ICH-volume was 10.5mL (IQR 5.1; 23.8) No device-related adverse events occurred.

Conclusions

Minimally-invasive endoscopy guided surgery within 8 hours after symptom onset for supratentorial ICH is safe and can reduce ICH-volume. Randomized controlled trials are needed to assess its effect on functional outcome.

Funding: Netherlands Cardiovascular Research Initiative, supported by: Dutch Heart Foundation, (CVON2015-01), Penumbra Inc. (www.dutch-ich.nl )

Trial Registration Number

NCT03608423

Background And Aims

Stabilizing spontaneous intracerebral hemorrhage (ICH) prior to minimally invasive surgery seems intuitive, but is not established. We investigated time course, risk factors and outcomes associated with hematoma expansion (HE) pre (PreR)- and post (PostR)- randomization from two clinical trials with serial imaging.

Methods

We pooled individual patient data from the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE II/III) trials with 640 patients and ICH volume >20 mL to stringently determine end of ICH/IVH expansion.

Results

Median[IQR] diagnostic ICH volume was 40.4[29.5, 54.1] mL. PreR HE >6mL/>33% was detected in 216(33.8%)/156(24.4%) subjects. Time to hematoma stability from symptom onset was 11.4[7.3, 19.3] hours. Of subjects with expansion, final events occurred after 12 hours from symptom onset in 52.3%. PostR ICH expansion occurred in 27 patients (4.2%), who were more likely to have PreR HE (58.3% vs 33.9%; p=0.014); groups behaved similarly. Time to ICH stability was longer for patients with PostR expansion versus those without (20.2[15.1, 38.1] vs 11.1[7.3, 18.6] hours; p<0.001). End of treatment (EOT) ICH volume was larger in surgical MISTIE III cases with PostR ICH expansion (n=7) versus those without (n=243) (52.6[23.3, 60.9] vs 16.7[9.3, 25.9] mL; p=0.002). Day 365 modified Rankin Scale comparing surgical patients with and without PostR ICH expansion was 5 [3,6] vs 4 [3,5]; p=0.072).

Conclusions

Half of spontaneous hematomas stabilize within 12 hours after ictus and 85% by 24 hours. With stabilization, subsequent bleeding events were infrequent. PostR bleeding events were associated with longer times to stabilization.

Trial Registration Number

The abstract uses data from the following two clinical trials:

NCT01827046 and NCT00224770

Background And Aims

Whether certain activities can trigger vessel rupture causing spontaneous intracerebral hemorrhage (ICH) remains unknown. We assessed whether certain trigger factors increase the risk for ICH onset.

Methods

We included patients diagnosed with ICH between July 1, 2013 and December 31, 2019. We interviewed patients on the occurrence of potential trigger factors using a structured questionnaire. With the case-crossover design, we calculated relative risks (RR) and the population-attributable fractions (PAF) for potential trigger factors for ICH.

Results

We interviewed 149 patients (mean age 64, 66% male) with ICH. Sixty-seven (45%) had a lobar hemorrhage, 60 (40%) had a deep hemorrhage, 19 (13%) had a cerebellar hemorrhage, and 3 (2%) had an intraventricular hemorrhage. For ICH in general, there was an increased risk within an hour after caffeine consumption (RR=2.5, 95% confidence interval (CI)=1.8-3.6, PAF=27.7%), after coffee consumption alone (RR=4.8, 95%CI=3.3-6.9, PAF=33.9%), after lifting >25kg (RR=6.6, 95%CI=2.2-19.9, PAF=6.0%), after minor head trauma (RR=10.1, 95%CI=1.7-60.2, PAF=1.2%), after sexual activity (RR=30.4, 95%CI=16.8-55.0, PAF=9.1%), after straining for defecation (RR=37.6, 95%CI=22.4-63.4, PAF=17.0%), and after vigorous exercise (RR=21.8, 95%CI=12.6-37.8, PAF=18.2%). Within 24 hours after flu-like disease or fever the risk for ICH was also increased (RR=50.7, 95%CI=27.1-95.1, PAF=13.6%). The RR for all Valsalva maneuvers combined was 3.5 (95%CI=1.7-6.9) in deep hemorrhages and 2.0 (95%CI=0.9-4.2) in lobar hemorrhages.

Conclusions

We identified several blood pressure related trigger factors and one infectious trigger factor for ICH onset, providing new insights into the pathophysiology of vessel rupture resulting in ICH.

Trial Registration Number

Not applicable