Re-evaluating patient communication and care in angiographically negative subarachnoid hemorrhage: Balancing realism and optimism.

Angiographically negative subarachnoid hemorrhage (anSAH) has traditionally been considered a benign condition, mainly because of favorable outcomes in the acute stage in comparison to the often negative acute outcomes of aneurysmal subarachnoid hemorrhage. However, a growing body of research in recent years shows that anSAH often leads to cognitive impairments, emotional distress, and difficulties in resuming work or other daily life activities. Therefore, in this position paper, we call for a change in neurological care and a shift in patient communication, emphasizing the importance of addressing patient needs and fostering realistic expectations rather than solely focusing on the benign nature of the condition.

Relationship Between Hemorrhage Type and Development of Emotional and Behavioral Dyscontrol After Hemorrhagic Stroke.

OBJECTIVE: Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke are heavily weighted toward ischemic stroke. This study was designed to compare risk of EBD following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and to identify risk factors for EBD following hemorrhagic stroke. METHODS: The authors conducted a prospective cohort study of patients hospitalized for nontraumatic hemorrhagic stroke between 2015 and 2021. Patients or legally authorized representatives completed the Quality of Life in Neurological Disorders (Neuro-QOL) EBD short-form inventory 3 months after hospitalization. Univariable and multivariable analyses identified risk factors for EBD after hemorrhagic stroke. RESULTS: The incidence of EBD was 21% (N=15 of 72 patients) at 3 months after hemorrhagic stroke. Patients with ICH were more likely to develop EBD; 93% of patients with EBD (N=14 of 15) had ICH compared with 56% of patients without EBD (N=32 of 57). The median Glasgow Coma Scale (GCS) score at hospital admission was lower among patients who developed EBD (13 vs. 15 among those without EBD). Similarly, admission scores on the National Institutes of Health Stroke Scale (NIHSS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were higher among patients with EBD (median NIHSS score: 7 vs. 2; median APACHE II score: 17 vs. 11). Multivariable analyses identified hemorrhage type (ICH) and poor admission GCS score as predictors of EBD 3 months after hemorrhagic stroke. CONCLUSIONS: Patients with ICH and a low GCS score at admission are at increased risk of developing EBD 3 months after hemorrhagic stroke and may benefit from early intervention.

Cognitive, Mental Health, Functional, and Quality of Life Outcomes 1 Year After Spontaneous Subarachnoid Hemorrhage: A Prospective Observational Study.

BACKGROUND: Patients with spontaneous subarachnoid hemorrhage (SAH) frequently encounter cognitive dysfunction and mental health issues with negative effects on health-related quality of life (HR-QoL). Here, we aimed to describe the prevalence of cognitive deficits, mental health problems, and HR-QoL impairments 1 year after SAH. METHODS: In this prospective observational study, 177 patients with SAH admitted to our neurointensive care unit over a time span of ten years followed the invitation for an in-person 1-year follow-up, including a standardized neuropsychological test battery. Mental health issues (anxiety and depression) and HR-QoL were evaluated using questionnaires (Hospital Anxiety and Depression Scale; 36-item Short Form questionnaire). Functional outcome was assessed with the modified Rankin Scale (mRS) score. RESULTS: Patients were 54 years of age (interquartile range 47-62 years) and presented with a median Hunt and Hess score of 2 (interquartile range 1-3) at admission. Most patients (93%) achieved good functional 1-year outcomes (mRS score 0-2). Seventy-one percent of patients had deficits in at least one cognitive domain, with memory deficits being the most prevalent (51%), followed by deficits in executive functions (36%), visuoconstruction (34%), and attention (21%). Even patients with perimesencephalic SAH (18%) or with full functional recovery (mRS score = 0, 46%) had a comparable prevalence of cognitive deficits (61% and 60%, respectively). Symptoms of depression and anxiety were reported by 16% and 33% of patients, respectively. HR-QoL was impaired in 37% (55 of 147). Patients with cognitive deficits (p = 0.001) or mental health issues (p < 0.001) more frequently reported impaired HR-QoL. CONCLUSIONS: Most patients with SAH have cognitive deficits and mental health issues 1 year after SAH. These deficits impair patients' quality of life.

Negative disease-related stigma 3-months after hemorrhagic stroke is related to functional outcome and female sex.

OBJECTIVES: The objective of this study was to determine factors associated with negative disease-related stigma after hemorrhagic stroke. MATERIALS AND METHODS: Patients with non-traumatic hemorrhage (ICH or SAH) admitted between January 2015 and February 2021 were assessed by telephone 3-months after discharge using the Quality of Life in Neurological Disorders (Neuro-QoL) Negative Disease-Related Stigma Short Form inventory. We evaluated the relationship between disease-related stigma (T-score >50) and pre-stroke demographics, admission data, and poor functional outcome (3-month mRS score 3-5 and Barthel Index <100). RESULTS: We included 89 patients (56 ICH and 33 SAH). The median age was 63 (IQR 50-69), 43 % were female, and 67 % graduated college. Admission median GCS score was 15 (IQR 13-15) and APACHE II score was 12 (IQR 9-17). 31 % had disease-related stigma. On univariate analysis, disease-related stigma was associated with female sex, non-completion of college, GCS score, APACHE II score, and 3-month mRS score (all p < 0.05). On multivariate analysis, disease-related stigma was associated with female sex (OR = 3.72, 95 % CI = 1.23-11.25, p = 0.02) and 3-month Barthel Index <100 (OR = 3.46, 95 % CI = 1.13-10.64, p = 0.03) on one model, and female sex (OR = 3.75, 95 % CI = 1.21-11.58, p = 0.02) and 3-month mRS score 3-5 (OR = 4.23, 95 % CI = 1.21-14.75, p = 0.02) on a second model. CONCLUSION: Functional outcome and female sex are associated with disease-related stigma 3-months after hemorrhagic stroke. Because stigma may negatively affect recovery, there is a need to understand the relationship between these factors to mitigate stroke-related stigma.

Neutrophil Enzyme Myeloperoxidase Modulates Neuronal Response in a Model of Subarachnoid Hemorrhage by Venous Injury.

Background and Purpose: Aneurysmal subarachnoid hemorrhage (SAH) is associated with the development of delayed cognitive deficits. Neutrophil infiltration into the central nervous system is linked to the development of these deficits after SAH. It is however unclear how neutrophil activity influences central nervous system function in SAH. The present project aims to elucidate which neutrophil factors mediate central nervous system injury and cognitive deficits after SAH. Methods: Using a murine model of SAH and mice deficient in neutrophil effector functions, we determined which neutrophil effector function is critical to the development of deficits after SAH. In vivo and in vitro techniques were used to investigate possible pathways of neutrophils effect after SAH. Results: Our results show that mice lacking functional MPO (myeloperoxidase), a neutrophil enzyme, lack both the meningeal neutrophil infiltration (wild type, sham 872 cells/meninges versus SAH 3047, P=0.023; myeloperoxidase knockout [MPOKO], sham 1677 versus SAH 1636, P=NS) and erase the cognitive deficits on Barnes maze associated with SAH (MPOKO sham versus SAH, P=NS). The reintroduction of biologically active MPO, and its substrate hydrogen peroxide (H2O2), to the cerebrospinal fluid of MPOKO mice at the time of hemorrhage restores the spatial memory deficit observed after SAH (time to goal box MPOKO sham versus MPOKO+MPO/H2O2, P=0.001). We find evidence of changes in neurons, astrocytes, and microglia with MPO/H2O2 suggesting the effect of MPO may have complex interactions with many cell types. Neurons exposed to MPO/H2O2 show decreased calcium activity at baseline and after stimulation with potassium chloride. Although astrocytes and microglia are affected, changes seen in astrocytes are most consistent with inflammatory changes that likely affect neurons. Conclusions: These results implicate MPO as a mediator of neuronal dysfunction in SAH through its effect on both neurons and glia. These results show that, in SAH, the activity of innate immune cells in the meninges modulates the activity and function of the underlying brain tissue.

Ponesimod protects against neuronal death by suppressing the activation of A1 astrocytes in early brain injury after experimental subarachnoid hemorrhage.

As an important initiator and responder of brain inflammation in the central nervous system (CNS), astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression and secretion profiles, termed detrimental A1 and beneficial A2. Inflammatory events have been shown to occur during the phase of early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the phenotype transformation of astrocytes as well as its potential contribution to inflammatory status in the EBI of SAH has yet to be determined. In the present study, both in vivo and in vitro models of SAH were established, and the polarization of astrocytes after SAH was analyzed by RNA-seq, western blotting, and immunofluorescence staining. The effect of astrocytic phenotype transformation on neuroinflammation was examined by real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). We demonstrated that astrocytes were transformed into A1 astrocytes and caused neuronal death through the release of pro-inflammatory factors in EBI after SAH. Importantly, Ponesimod, an S1PR1 specific modulator, exerted neuroprotective effects through the prevention of astrocytic polarization to the A1 phenotype as proved by immunofluorescence, neurological tests, and TUNEL study. We also revealed the role of Ponesimod in modulating astrocytic response was mediated by the signal transducer and activator of transcription 3 (STAT3) signaling. Our study suggested that Ponesimod may be a promising therapeutic target for the treatment of brain injury following SAH.

Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage-a feasibility series.

The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1-10. CGRP levels were determined via competitive enzyme immunoassay and calculated as "area under the curve" (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11-35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

Involvement of Cerebral Blood Flow on Neurological and Behavioral Functions after Subarachnoid Hemorrhage in Mice.

OBJECTIVE: Cerebral Blood Flow (CBF) change after Subarachnoid Hemorrhage (SAH) is strongly associated with brain injuries such as early brain injury and delayed cerebral ischemia. We evaluated the correlation between CBF using Laser Speckle Flow Imaging (LSFI) after SAH and neurological findings in the sub-acute phase. METHOD: An SAH was induced by endovascular perforation in male mice. CBF was quantitatively measured by using LSFI at six time points, immediately to 14 days after SAH induction. Behavior tests and survival rate were evaluated. The mice were divided into recovery and hypo-perfusion groups according to their CBF at 1 day after the procedure. RESULT: Forty mice were included in this study. Five mice (20%) were included in the hypo-perfusion group, and the remaining 20 (80%) mice were classified as the recovery group. The decrease of CBF in the recovery group was observed until 1 day after the procedure. However, the decrease of CBF in the hypo-perfusion group was prolonged until 7 days after the procedure. Neurological findings and survival rates in the hypo-perfusion group were significantly worse than those in the recovery group. The low alternation cases (≤ 50%) in the Y-maze test in the recovery group (n = 5) had significantly lower CBF at 1 day after the procedure. CONCLUSION: Low blood flow at 1 day after SAH was associated with worse survival rate, neurological findings, and memory disturbance. Early improvement in CBF may be associated with an improved prognosis after SAH.

Neuroprotective roles of total flavones of Camellia on early brain injury andcognitive dysfunction following subarachnoid hemorrhage in rats.

The present study was undertaken to explore the role of total flavones of Camellia (TFC) on cerebral injury following subarachnoid hemorrhage (SAH) in rats. We showed that the increase of malondialdehyde (MDA) level in brain tissues, leakages of neuron-specifc enolase (NSE) and lactate dehydrogenase (LDH) from brain tissues to serum at 48 h after SAH were significantly blocked by TFC treatment. Besides, TFC treatment could reduce brain edema and the Bax/Bcl-2 ratio in hippocampal tissues at mRNA and protein levels at 48 h after SAH. In addition, and the reduction of neurological scores at 7d after SAH were significantly inhibited by TFC treatment. We next sought to demonstrate the role of TFC on cognitive rehabilitation and the tau phosphorylation in hippocampal tissues at 30d after SAH. Not surprisingly, cognitive dysfunction and the upregulation of tau phosphorylation at Ser262 (p-tau-Ser262) in hippocampal tissues were markedly reduced by TFC treatment. These findings suggested that TFC has protective effect on SAH-induced EBI and subsequent cognitive dysfunction, which may be related to downregulating the Bax/Bcl-2-related apoptosis pathway and inhibition of tau phosphorylation.

Gray-to-white matter ratio predicts long-term recovery potential of patients with aneurysmal subarachnoid hemorrhage.

Predicting recovery potential of patients with aneurysmal subarachnoid hemorrhage (aSAH) is challenging. We investigated whether the gray-to-white matter ratio (GWR) predicts recovery of cognitive function (CF) and quality of life (QOL) of these patients. We analyzed data of 69 patients with aSAH. Patients' demographics, comorbidities, and neurological status were recorded. One year after aSAH, Montreal Cognitive Assessment (MoCA) and Short Form-36 (SF-36) tests were administered to the patients, and brain volumes of patients were examined using MRI. Three years after aSAH, MoCA and SF-36 tests were conducted again. Differences between the test scores 1 and 3 years after aSAH were evaluated (ΔMoCA and ΔSF-36). Patients with ΔMoCA ≥ 4 points and those with ΔSF-36 ≥ 8 points were referred to as good MoCA and SF-36 recovery, respectively. ΔMoCA correlated with GWR in male and female patients (females: p < 0.001, R2 = 0.581; males: p < 0.001, R2 = 0.481). In female patients, GWR > 1.34 predicted good MoCA recovery with 82.3% sensitivity and 80% specificity, and in male patients, GWR > 1.36 predicted good MoCA recovery with 80% sensitivity and 95% specificity. ΔSF-36 correlated with GWR in male and female patients (females: p < 0.001, R2 = 0.479; males: p < 0.001, R2 = 0.627). In female patients, GWR > 1.35 predicted good SF-36 recovery with 74% sensitivity and 84% specificity, and in male patients, GWR > 1.38 predicted good SF-36 recovery with 72% sensitivity and 92% specificity. GWR is a good predictor of the recovery of CF and QOL in patients with aSAH and, thus, can help physicians to better organize rehabilitation of patients.

Subarachnoid Hemorrhage is Followed by Pituitary Gland Volume Loss: A Volumetric MRI Observational Study.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating disease associated with high mortality and morbidity. Besides neurological sequelae, neuropsychological deficits largely contribute to patients' long-term quality of life. Little is known about the pituitary gland volume (PGV) after SAH compared to healthy referents and the association of PGV with long-term outcome including cognitive function. METHODS: Sixty consecutive non-traumatic SAH patients admitted to the neurological intensive care unit between 2010 and 2014 were enrolled. 3-Tesla magnetic resonance imagining was performed at baseline (16 days) and 12 months after SAH to measure PGV semi-automatically using the software iPlan Net 3.5.0. PGV was compared to age and sex matched healthy referents. The difference between baseline and 1-year-PGV was classified as increase (> 20 mm3 PGV increase), stable (± 20 mm3), or decrease (> 20 mm3 PGV decrease). In addition, total intracerebral volume was calculated. Neuropsychological testing was applied in 43 SAH patients at 1-year follow up encompassing several domains (executive, attention, memory) and self-assessment (questionnaire for self-perceived deficits in attention [German: FEDA]) of distractibility in mental processes, fatigue and decrease in motivation. Multivariable regression with multivariable generalized linear models was used for comparison of PGVs and for subgroup analysis to evaluate a potential association between PGV and neuropsychological outcome. RESULTS: Patients were 53 years old (IQR = 44-63) and presented with a median Hunt&Hess grade of 2 (IQR = 1-3). SAH patients had a significantly lower PGV both at baseline (360 ± 19 mm3, p < 0.001) and 1 year (367 ± 18 mm3p < 0.001) as compared to matched referents (mean 505 ± 18 mm3). PGV decreased by 75 ± 8 mm3 in 28 patients, increased by 120 ± 22 mm3 in 22 patients and remained stable in 10 patients at 1-year follow-up. PGV in patients with PGV increase at 12 months was not different to healthy referents (p = 0.062). Low baseline PGV was associated with impaired executive functions at 1 year (adjOR = 8.81, 95%-CI = 1.46-53.10, p = 0.018) and PGV decrease within 1 year was associated with self-perceived worse motivation (FEDA; Wald-statistic = 6.6, df = 1, p = 0.010). CONCLUSIONS: Our data indicate significantly lower PGVs following SAH. The association of sustained PGV decrease with impaired neuropsychological long-term outcome warrants further investigations including neuroendocrine hormone measurements.

Neurocognitive Outcomes in a Cisternal Blood Injection Murine Model of Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model. METHODS: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus. RESULTS: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus. CONCLUSIONS: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH.

Severe cognitive impairment in aneurysmal subarachnoid hemorrhage: Predictors and relationship to functional outcome.

BACKGROUND: Cognitive impairment is common after aneurysmal subarachnoid hemorrhage (SAH). However, compared to predictors of functional outcome, meaningful predictors of cognitive impairment are lacking. OBJECTIVE: Our goal was to assess which factors during hospitalization can predict severe cognitive impairment in SAH patients, especially those who might otherwise be expected to have good functional outcomes. We hypothesized that the degree of early brain injury (EBI), vasospasm, and delayed neurological deterioration (DND) would predict worse cognitive outcomes. METHODS: We retrospectively reviewed SAH patient records from 2013 to 2019 to collect baseline information, clinical markers of EBI (Fisher, Hunt-Hess, and Glasgow Coma scores), vasospasm, and DND. Cognitive outcome was assessed by Montreal Cognitive Assessment (MoCA) and functional outcomes by modified Rankin Scale (mRS) at hospital discharge. SAH patients were compared to non-neurologic hospitalized controls. Among SAH patients, logistic regression analysis was used to identify predictors of severe cognitive impairment defined as a MoCA score <22. RESULTS: We screened 288 SAH and 80 control patients. Cognitive outcomes assessed via MoCA at discharge were available in 105 SAH patients. Most of these patients had good functional outcome at discharge with a mean mRS of 1.8±1.3. Approximately 56.2% of SAH patients had MoCA scores <22 compared to 28.7% of controls. Among SAH patients, modified Fisher scale was an independent predictor of cognitive impairment after adjustment for baseline differences (OR 1.638, p=0.043). MoCA score correlated inversely with mRS (r=-0.3299, p=0.0006); however, among those with good functional outcome (mRS 0-2), 48.7% still exhibited cognitive impairment. CONCLUSIONS: Severe cognitive impairment is highly prevalent after SAH, even among patients with good functional outcome. Higher modified Fisher scale on admission is an independent risk factor for severe cognitive impairment. Cognitive screening is warranted in all SAH patients, regardless of functional outcome.

[Long-term neuropsychological and participation impairment after aneurysmal subarachnoid hemorrhage (aSAH)]. / Neuropsychologische Langzeitfolgen und Teilhabestörungen nach aneurysmatischer Subarachnoidalblutung (aSAB).

The present review focuses on cognitive and participation impairments after aneurysmal subarachnoidal hemorrhage (aSAH). Such impairments may be present even in cases without evidence of damage in the neuropsychologically expected brain area. Neuroinflammation and oxidative stress may be responsible for this finding. Most frequently, cognitive impairment can be found in the verbal memory domain, visuospatial skills and memory domain, attention and working memory domain, executive functions (planning, central control, problem solving, attention, decision making), psychomotor speed and language domain. The presence of cognitive deficits is a major risk factor not to return to work again. Together with cognitive impairment, psychiatric symptoms like anxiety, depression and fatigue may be observed. Psychiatric disturbances result in impairments of social and vocational participation and - consecutively - worsening of quality of life.

Serum Ngb (Neuroglobin) Is Associated With Brain Metabolism and Functional Outcome of Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- Hypoxic-ischemic brain damage is a well-recognized physiopathologic mechanism after aneurysmal subarachnoid hemorrhage (aSAH). The Ngb (neuroglobin) is a hemoprotein predominantly expressed in the brain with a high affinity for oxygen. Relationship between serum Ngb level and brain metabolism in aSAH patients has not been investigated previously. Methods- Thirty-six consecutive severe aSAH patients (Glasgow Coma Scale score ≤8 on admission) with multimodal neuromonitoring and 36 matched healthy subjects were included. Serum Ngb level was analyzed in combination with other time-matched cerebral microdialysis parameters, brain tissue oxygen tension, and 12-month neurological outcomes. Results- Serum Ngb level was correlated positively with cerebral microdialysis parameters and brain tissue oxygen tension ( P<0.001). Poor functional outcome (modified Rankin Scale score >3) 12 months after aSAH was associated with higher Ngb level but independent of age, sex, and disease severity ( P<0.001). A similar association was found between high Ngb level and neuropsychological test results indicative of impairments in cognition, visual conceptualization, and frontal executive functions ( P<0.001). Conclusions- Ngb may be a potential biomarker for reflecting brain tissue oxygen tension, brain metabolism, and functional outcome in severe aSAH patients and merits further study in the context of aSAH.

Analgesic treatment limits surrogate parameters for early stress and pain response after experimental subarachnoid hemorrhage.

BACKGROUND: In animal research, authorities require a classification of anticipated pain levels and a perioperative analgesia protocol prior to approval of the experiments. However, data on this topic is rare and so is the reported use of analgesics. We determined surrogate parameters of pain and general well-being after subarachnoid hemorrhage (SAH), as well as the potential for improvement by different systemic analgesia paradigms. Brain injury was induced by filament perforation to mimic SAH. Sham-operated mice were included as surgical control groups with either neck or no-neck preparation. Mice with controlled cortical impact (CCI) injury were included as a control group with traumatic brain injury (TBI), but without neck preparation. Mice were randomized to buprenorphine, carprofen, meloxicam, or vehicle treatment. 24 h after SAH, CCI or sham surgery, pain and stress levels were assessed with a visual assessment score and the amount of food intake was recorded. RESULTS: Neck preparation, which is required to expose the surgical field for SAH induction, already increased pain/stress levels and sham surgeries for both CCI and SAH reduced food intake. Pain/stress levels were higher and food intake was lower after SAH compared with CCI. Pain/stress levels after CCI without analgesic treatment were similar to levels after SAH sham surgery. Pain treatment with buprenorphine was effective to reduce pain after SAH, whereas lower pain/stress intensity levels after CCI were not improved. CONCLUSION: This study emphasizes the importance of pain and stress assessment after surgeries and the efficacy of buprenorphine to improve pain and comfort levels after experimental SAH.

Symptoms and consequences of subarachnoid haemorrhage after 7 years.

OBJECTIVES: Short-term follow-up studies after a subarachnoid haemorrhage (SAH) have shown impaired cognition, fatigue, depression and anxiety, but less is known regarding long-term consequences. The aim of this study was to investigate health outcomes in persons 7 years after SAH. MATERIALS AND METHODS: This is a descriptive cohort follow-up study of persons with non-traumatic SAH treated at Sahlgrenska University Hospital, Gothenburg, Sweden. The follow-up was conducted 7 years post-treatment and included home visits using forms and questionnaires about health outcomes; the Barthel Index (BI), modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA) and Multidimensional Fatigue Inventory (MFI). RESULTS: Seven years post-SAH, 33 persons fulfilled the inclusion criteria, of whom 18 (55%) participated (median age 63 years). Cognitive impairment was present in 11 participants, assessed with the MoCA, where the item of delayed recall was most difficult. The majority (n = 16) were independent in activities of daily living (ADL), and few (n = 3) had physical symptoms according to the NIHSS. However, three participants were free from disability according to the mRS. Nearly, half of the participants had symptoms of anxiety (n = 8). Three had symptoms of depression and more than half experienced fatigue. CONCLUSION: The physical function and independency in ADL is high among long-term SAH survivors. Despite this, only a few were completely free from disability, and the main problems 7 years after SAH were cognitive impairment and anxiety.

Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units and can be assessed by the Richmond Agitation and Sedation Scale (RASS) in principle. However, the role of agitation in patients with aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a retrospective analysis to identify risk factors for the development of a hyperactive delirium and its functional consequences for neurological outcome. Three hundred thirty-eight patients with SAH were screened in this study resulting in 212 patients which reached at least once a RASS of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up. We provide four independent risk factors for the development of agitation in SAH patients. Our study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients.

Review: Post-Intensive Care Syndrome: Unique Challenges in the Neurointensive Care Unit.

Within the last couple of decades, advances in critical care medicine have led to increased survival of critically ill patients, as well as the discovery of notable, long-term health challenges in survivors and their loved ones. The terms post-intensive care syndrome (PICS) and PICS-family (PICS-F) have been used in non-neurocritical care populations to characterize the cognitive, psychiatric, and physical sequelae associated with critical care hospitalization in survivors and their informal caregivers (e.g., family and friends who provide unpaid care). In this review, we first summarize the literature on the cognitive, psychiatric, and physical correlates of PICS and PICS-F in non-neurocritical patient populations and draw attention to their long-term negative health consequences. Next, keeping in mind the distinction between disease-related neurocognitive changes and those that are associated directly with the experience of a critical illness, we review the neuropsychological sequelae among patients with common neurocritical illnesses. We acknowledge the clinical factors contributing to the difficulty in studying PICS in the neurocritical care patient population, provide recommendations for future lines of research, and encourage collaboration among critical care physicians in all specialties to facilitate continuity of care and to help elucidate mechanism(s) of PICS and PICS-F in all critical illness survivors. Finally, we discuss the importance of early detection of PICS and PICS-F as an opportunity for multidisciplinary interventions to prevent and treat new neuropsychological deficits in the neurocritical care population.

Psychosocial Comorbidities Related to Return to Work Rates Following Aneurysmal Subarachnoid Hemorrhage.

Purpose Ability to return to work (RTW) after stroke has been shown to have positive psychosocial benefits on survivors. Although one-fifth of aneurysmal subarachnoid hemorrhage (aSAH) survivors suffer from poor psychosocial outcomes, the relationship between such outcomes and RTW post-stroke is not clear. This project explores the relationship between age, gender, race, marital status, anxiety and depression and RTW 3 and 12 months post-aSAH. Methods Demographic and clinical variables were collected from the electronic medical record at the time of aSAH admission. Anxiety and depression were assessed at 3 and 12 months post-aSAH using the State Trait Anxiety Inventory (STAI) and Beck's Depression Inventory-II (BDI-II) in 121 subjects. RTW for previously employed patients was dichotomized into yes/no at their 3 or 12 month follow-up appointment. Results Older age was significantly associated with failure to RTW at 3 and 12 months post-aSAH (p = 0.003 and 0.011, respectively). Female gender showed a trending but nonsignificant relationship with RTW at 12 months (p = 0.081). High scores of depression, State anxiety, and Trait anxiety all had significant associations with failure to RTW 12 months post-aSAH (0.007 ≤ p ≤ 0.048). At 3 months, there was a significant interaction between older age and high State or Trait anxiety with failure to RTW 12 months post-aSAH (p = 0.025, 0.042 respectively). Conclusions Patients who are older and suffer from poor psychological outcomes are at an increased risk of failing to RTW 1-year post-aSAH. Our interactive results give us information about which patients should be streamlined for therapy to target their psychosocial needs.