Impact of Posterior Wall Isolation During AF Ablation on the Incidence of Left Atrial Flutter.

BACKGROUND: Linear and complex electrogram ablation (LCEA) beyond pulmonary vein isolation (PVI) is associated with an increase in left atrial macro-re-entrant tachycardias (LAMTs). Posterior wall isolation (PWI) is increasingly performed to improve AF ablation outcomes. However, the impact of PWI on the incidence of LAMT is unknown. OBJECTIVES: The purpose of this study was to establish the incidence of LAMT following PVI alone vs PVI + PWI vs PVI + PWI + LCEA. METHODS: Consecutive patients undergoing catheter ablation for AF or LAMT post-AF ablation between 2008 and 2022 from 4 electrophysiology centers were reviewed with a minimum follow-up of 12 months. RESULTS: In total, 5,619 (4,419 index, 1,100 redo) AF ablation procedures were performed in 4,783 patients (mean age 60.9 ± 10.6 years, 70.7% men). Over a mean follow-up of 6.4 ± 3.8 years, 246 procedures for LAMT were performed in 214 patients at a mean of 2.6 ± 0.6 years post-AF ablation. Perimitral (52.8% of patients), roof-dependent (27.1%), PV gap-related (17.3%), and anterior circuits (8.9%) were most common, with 16.4% demonstrating multiple circuits. The incidence of LAMT was significantly higher following PVI + PWI (6.2%) vs PVI alone (3.0%; P < 0.0001) and following PVI + PWI + LCEA vs PVI + PWI (12.5%; P = 0.019). Conduction gaps in previous ablation lines were responsible for LAMT in 28.4% post-PVI alone, 35.3% post-PVI + PWI (P = 0.386), and 81.8% post-PVI + PWI + LCEA (P < 0.005). CONCLUSIONS: The incidence of LAMT following PVI + PWI is higher than with PVI alone but significantly lower than with more extensive atrial substrate modification. Given a low frequency of LAMT following PWI, empiric mitral isthmus ablation is not justified and may be proarrhythmic.

Hydrogen Activation with Ru-PN3P Pincer Complexes for the Conversion of C1 Feedstocks.

The hydrogenation of C1 feedstocks (CO and CO2) has been investigated using ruthenium complexes [RuHCl(CO)(PN3P)] as the catalyst. PN3P pincer ligands containing amines in the linker between the central pyridine donor and the phosphorus donors with bulky substituents (tert-butyl (1) or TMPhos (2)) are required to obtain mononuclear single-site catalysts that can be activated by the addition of KOtBu to generate stable five-coordinate complexes [RuH(CO)(PN3P-H)], whereby the pincer ligand has been deprotonated. Activation of hydrogen takes place via heterolytic cleavage to generate [RuH2(CO)(PN3P)], but in the presence of CO, coordination of CO occurs preferentially to give [RuH(CO)2(PN3P-H)]. This complex can be protonated to give the cationic complex [RuH(CO)2(PN3P)]+, but it is unable to activate H2 heterolytically. In the case of the less coordinating CO2, both ruthenium complexes 1 and 2 are highly efficient as CO2 hydrogenation catalysts in the presence of a base (DBU), which in the case of the TMPhos ligand results in a TON of 30,000 for the formation of formate.

Caudal fluoroscopic guidance for the insertion of transvenous pacing leads.

BACKGROUND: Pneumothorax is a well-recognized complication of cardiac implantable electronic device (CIED) insertion. While AP fluoroscopy alone is the most commonly imaging technique for subclavian or axillary access, caudal fluoroscopy (angle 40°) is routinely used at our institution. The caudal view provides additional separation of the first rib and clavicle and may reduce the risk of pneumothorax. We assessed outcomes at our institution of AP and caudal fluoroscopic guided pacing lead insertion. METHODS: Retrospective cohort study of consecutive patients undergoing transvenous lead insertion for pacemakers, defibrillators, and cardiac resynchronization therapy devices between 2011 and 2023. Both de novo and lead replacement/upgrade procedures were included. Data were extracted from operative, radiology, and discharge reports. All patients underwent postprocedure chest radiography. RESULTS: Three thousand two hundred fifty-two patients underwent insertion of pacing leads between February 2011 and March 2023. Mean age was 71.1 years (range 16-102) and 66.7% were male. Most (n = 2536; 78.0%) procedures used caudal guidance to obtain venous access, while 716 (22.0%) procedures used AP guidance alone. Pneumothoraxes occurred in five (0.2%) patients in the caudal group and five (0.7%) patients in the AP group (p = .03). Subclavian contrast venography was performed less frequently in the caudal group (26.2% vs. 42.7%, p < .01). CONCLUSION: Caudal fluoroscopy for axillary/subclavian access is associated with a lower rate of pneumothorax and contrast venography compared with an AP approach.

Transvenous versus subcutaneous implantable cardioverter defibrillators in young cardiac arrest survivors.

Secondary prevention implantable cardioverter defibrillators (ICDs) are indicated in young patients presenting with aborted sudden cardiac death (SCD) because of ventricular arrhythmias. Transvenous-ICDs (TV-ICDs) are effective, established therapies supported by evidence. The significant morbidity associated with transvenous leads led to the development of the newer subcutaneous-ICD (S-ICD). This review discusses the clinical considerations when selecting an ICD for the young patient presenting with out-of-hospital cardiac arrest. The major benefits of TV-ICDs are their ability to pace (antitachycardia pacing [ATP], bradycardia support and cardiac resynchronisation therapy [CRT]) and the robust evidence base supporting their use. Other benefits include a longer battery life. Significant complications associated with transvenous leads include pneumothorax and tamponade during insertion and infection and lead failure in the long term. Comparatively, S-ICDs, by virtue of having no intravascular leads, prevent these complications. S-ICDs have been associated with a higher incidence of inappropriate shocks. Patients with an indication for bradycardia pacing, CRT or ATP (documented ventricular tachycardia) are seen as unsuitable for a S-ICD. If venous access is unsuitable or undesirable, S-ICDs should be considered given the patient is appropriately screened. There is a need for further randomised controlled trials to directly compare the two devices. TV-ICDs are an effective therapy for preventing SCD limited by significant lead-related complications. S-ICDs are an important development hindered largely by an inability to pace. Young patients stand to gain the most from a S-ICD as the cumulative risk of lead-related complications is high. A clinical framework to aid decision-making is presented.

Depression and anxiety in caregivers of patients with functional seizures.

OBJECTIVE: Contrary to patients, the psychological impact of functional seizures to caregivers has not been adequately investigated. This study aimed to evaluate the rates and determinants of depression and anxiety in caregivers of patients with functional seizures. METHODS: Patients with functional seizures and their caregivers completed surveys about demographic, disease-related, and psychosocial characteristics. Rates and determinants of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventory scores as dependent variables and patient and caregiver characteristics as independent variables. RESULTS: Twenty-nine patients (76% female, mean age of 37 years) and their caregivers (59% female, mean age of 43 years) were recruited. Symptoms of anxiety and/or depression were present in 96% of patients (96% depression, 92% anxiety) and 59% of caregivers (52% depression, 50% anxiety). Specifically, 31% of caregivers manifested mild depression, 14% moderate depression, and 7% severe depression, whereas 48% were not depressed. Similarly, 14% of caregivers manifested mild anxiety, 29% moderate anxiety, and 7% severe anxiety, whereas 50% were not anxious. Patient and caregiver depression levels strongly correlated (r = .73, p < .0001). The presence of anxiety and depression in the caregiver was associated with male patient gender (p = .02), patient depression level (p = .002), the caregiver being a parent or sibling (p = .02), and caregiver burden (p = .0009). SIGNIFICANCE: Caregivers of patients with functional seizures experience high rates of anxiety and depression, explained by specific demographic and psychosocial factors that could act as intervention targets.

Lateral lumbar interbody fusion - clinical outcomes, fusion rates and complications with recombinant human bone morphogenetic protein-2.

BACKGROUND: The authors report an Australian experience of lateral lumbar interbody fusion (LLIF) with respect to clinical outcomes, fusion rates, and complications, with recombinant human bone morphogenetic protein-2 (rhBMP-2) and other graft materials. METHODS: Retrospective cohort study of LLIF patients 2011-2021. LLIFs performed lateral decubitus by four experienced surgeons past their learning curve. Graft materials classified rhBMP-2 or non-rhBMP-2. Patient-reported outcomes assessed by VAS, ODI, and SF-12 preoperatively and postoperatively. Fusion rates assessed by CT postoperatively at 6 and 12 months. Complications classified minor or major. Clinical outcomes and complications analysed and compared between rhBMP-2 and non-rhBMP-2 groups. RESULTS: A cohort of 343 patients underwent 437 levels of LLIF. Mean age 67 ± 11 years (range 29-89) with a female preponderance (65%). Mean BMI 29kg/m2 (18-56). Most common operated levels L3/4 (36%) and L4/5 (35%). VAS, ODI and SF-12 improved significantly from baseline. Total complication rate 15% (53/343) with minor 11% (39/343) and major 4% (14/343). Ten patients returned to OR (2-wound infection, 8-further instrumentation and decompression). Most patients (264, 77%) received rhBMP-2, the remainder a non-rhBMP-2 graft material. No significant differences between groups at baseline. No increase in minor or major complications in the rhBMP-2 group compared to the non-rhBMP-2 group respectively; (10.6% vs 13.9% [p = 0.42], 2.7% vs 8.9% [p < 0.01]). Fusion rates significantly higher in the rhBMP-2 group at 6 and 12 months (63% vs 40%, [p < 0.01], 92% vs 80%, [p < 0.02]). CONCLUSION: LLIF is a safe and efficacious procedure. rhBMP-2 in LLIF produced earlier and higher fusion rates compared to available non-rhBMP-2 graft substitutes.

COVID-19 Recession: Young Adult Food Insecurity, Racial Disparities, and Correlates.

PURPOSE: The COVID-19 pandemic has inflicted devastating health, social, and economic effects globally. This study examines the experiences of young adults in the United States with respect to food insecurity during the pandemic and factors associated with higher and lower risk for young adult food insecurity. METHODS: Using the U.S. Census Bureau's Household Pulse Survey, a nationally representative survey collecting information on people's experiences throughout the pandemic, we analyzed prevalence of, and factors associated with young adult food insecurity during the pandemic. RESULTS: Overall, 13% of young adults aged 18-25 years reported often or sometimes not having enough to eat in the last 7 days at a given time during pandemic, on average, with Black and Hispanic young people facing higher rates of food insecurity (22% and 15%, respectively) than White non-Hispanic peers (11%). Over the observed pandemic period, we find a decline in food insecurity among young adults corresponding with economic policy actions. Factors associated with a higher risk of food insecurity include lower household income, expected job loss, renting as opposed to owning housing, behind on rent or mortgage payment, lack of confidence in an ability to pay next month's rent or mortgage, delayed medical care, and feeling worried or depressed. DISCUSSION: Our analyses reveal alarming levels of food insecurity among young adults, especially Black and Hispanic young people. Policy actions should include multifaceted and sustained interventions with a focus on supporting historically disenfranchised youth and their communities. These should prevent and address food and housing insecurity and mental health needs holistically.

Translating Phenomenology of Psychogenic Nonepileptic Seizures Into Nosology: Insights From Patients' and Caregivers' Profiles.

BACKGROUND: Patients with psychogenic nonepileptic seizures (PNES) can be semiologically dichotomized into those with hyperkinetic and those with paucikinetic events. The objective of this study was to compare characteristics of patients with diverse phenomenology and their caregivers to evaluate for differences that could inform about disease nosology. METHODS: Patients and caregivers monitored at the Epilepsy Monitoring Unit completed surveys about sociodemographic and disease characteristics, treatment and health care utilization, physical and psychosocial impact, and epilepsy knowledge. Patients were classified into hyperkinetic versus paucikinetic based on their recorded events. Comparison of the 2 populations was performed using Student t test for continuous variables and Fischer exact test for categorical variables. RESULTS: Forty-three patients with Epilepsy Monitoring Unit confirmed PNES and 28 caregivers were enrolled. Patients with hyperkinetic events were more commonly non-White patients and necessitated greater caregiving time. Otherwise, no statistically significant differences were seen between the 2 semiologically diverse groups of patients and caregivers in their sociodemographic (age, sex, employment, income, marital, and education) and disease (age of onset, duration, seizures frequency) characteristics, treatment (number of antiseizure medications before diagnosis, side effects) and health care utilization (emergency room visits, hospitalizations, clinic visits), physical (injuries) and psychosocial (depression, anxiety, quality of life, stigma, burden) characteristics, nor in their knowledge about seizures. CONCLUSIONS: Hyperkinetic events were more frequently encountered in non-White patients and required more caregiving time. Further research is required to elucidate if phenomenological dichotomy of PNES can inform about their nosological basis, and if it can guide treatment and define prognosis.

Depression and Anxiety in Adult Persons With Epilepsy and Their Caregivers: A Survey-Based Study at a Tertiary Care Center.

ABSTRACT: This study evaluated the rates of depression and anxiety and their determinants in adult persons with epilepsy and their caregivers. Both completed surveys about demographic, disease-related, and psychosocial characteristics. One hundred patients and caregivers participated. A mood disorder was present in 89% of patients and 56% of caregivers. In the univariate analysis, the presence of mood disorder in the patient was associated with being unmarried, unemployed, frequent hospitalizations, side effects from polypharmacy, patient stigma, patient quality of life, caregiver anxiety, and caregiver burden. In the multivariate analysis, medication side effects sustained as an important determinant. In the univariate analysis, the presence of mood disorder in the caregiver was associated with seizure frequency, patient anxiety, patient quality of life, caregiver stigma, and caregiver burden. In the multivariate analysis, patient anxiety level and caregiver burden sustained as important determinants. Adult persons with epilepsy and their caregivers experience high rates of mood disorders, explained by certain clinical factors.

Correlates of Housing Sustainability Among Youth Placed Into Permanent Supportive Housing and Rapid Re-Housing: A Survival Analysis.

PURPOSE: Youth experiencing homelessness (YEH) are vulnerable to multiple adverse health outcomes. Connecting YEH with housing is critical to addressing youth homelessness and to preventing long-term negative health consequences among this vulnerable population. Using administrative data, this study aims to explore correlates of YEH's sustainability in two major housing programs: permanent supportive housing (PSH) and rapid re-housing (RRH) programs. METHODS: This study used Homelessness Management Information System administrative data collected from 16 communities across the U.S. between January 1, 2015 and May 1, 2017 (n = 10,902). We conducted Cox proportional hazards survival analyses to explore correlates (e.g., demographics, homeless experiences, and overall vulnerability) of YEH's PSH (n = 577) and RRH (n = 2,883) sustainability separately. RESULTS: For YEH receiving PSH, only individuals' level of vulnerability is associated with greater hazard of exiting PSH. As for RRH sustainability, YEH who were 17 years old or younger, black or Latinx (as compared to white), of higher level of vulnerability, or previously spent most nights couch surfing or in transitional living programs (as compared to on the street) are associated with higher hazard of exiting RRH. CONCLUSIONS: Both PSH and RRH programs should incorporate comprehensive services targeting youth experiencing high vulnerability to prevent them from re-entering homelessness. Future RRH programming should also address housing sustainability disparities faced by racial and ethnic minority YEH, especially when they are disproportionately influenced by homelessness. Finally, RRH programs should incorporate services to foster independent living among younger YEH to sustain their housing status once temporary housing subsidies expire.

DDESVSFS: A simple, rapid and comprehensive screening tool for the Differential Diagnosis of Epileptic Seizures VS Functional Seizures.

OBJECTIVE: Functional seizures (FS) are often misclassified as epileptic seizures (ES). This study aimed to create an easy to use but comprehensive screening tool to guide further evaluation of patients presenting with this diagnostic dilemma. MATERIALS AND METHODS: Demographic, clinical and diagnostic data were collected on patients admitted for video-EEG monitoring for clarification of their diagnosis. Upon discharge, patients were classified as having ES vs FS. Using the collected characteristics and video-EEG diagnosis, we created a multivariable logistic regression model to identify predictors of ES. Then, we trained an integer-coefficient model with the most frequently selected predictors, creating a pointing system coined DDESVSFS, with scores ranging from -17 to +8 points. RESULTS: 43 patients with FS and 165 patients with ES were recruited. In the final integer-coefficient model, 8 predictors were identified as significant in differentiating ES from FS: normal electroencephalogram (-3 points), predisposing factors for FS (-3 points), increased number of comorbidities (-3 points), semiology suggestive of FS (-4 points), increased seizure frequency (-4 points), longer disease duration (+3 points), antiepileptic polypharmacy (+2 points) and compliance with antiepileptic drugs (+3 points). Cumulative scores of ≤ -9 points carried <5% predictive value for ES, while cumulative scores of ≥ -1 points carried >95% predictive value. The model performed well (AUC: 0.923, sensitivity: 0.945, specificity: 0.698). CONCLUSIONS: We propose DDESVSFS as a simple, rapid and comprehensive prediction score for the Differential Diagnosis of Epileptic Seizures VS Functional Seizures. Large prospective studies are needed to evaluate its utility in clinical practice.

Mind the gap: health disparities in families living with epilepsy are significant and linked to socioeconomic status.

There is limited information on disparities of people with epilepsy (PWE) and, foremost, their caregivers. The objective of this study was to comprehensively compare between PWE and caregivers with low socioeconomic status (SES) and those with high SES for disparities in demographic and epilepsy characteristics, treatment and health care utilization, physical and psychosocial impact, and knowledge about epilepsy. PWE and caregivers completed surveys about the aforementioned outcomes during their epilepsy clinic visit or epilepsy monitoring unit admission. Associations were evaluated using SES as a binary independent variable and the patient and caregiver related outcomes as dependent variables. Thirty-eight patients with low SES and 88 patients with high SES were recruited. Patients with low SES were more commonly non-white, uninsured, unemployed, of lower educational attainment and living in larger households. They were more likely to visit the emergency room for their seizures, were more frequently on polypharmacy and experienced more AED adverse effects. They exhibited higher depression and anxiety levels and worse quality of life. Twenty-two caregivers with low SES and 66 caregivers of high SAS were recruited. Caregivers with low SES were more likely to be non-white and single. They manifested poorer knowledge about epilepsy. There are notable inequalities in demographic, treatment-related and health care utilization aspects of care of PWE, as well as in the psychosocial impact of their disease. Additional demographic and epilepsy knowledge-related disparities are recognized in caregivers of PWE. Identification of those disparities is a critical step in the creation of appropriate interventions to eliminate them.

Stigma in psychogenic nonepileptic seizures.

OBJECTIVE: There is scarce literature on stigma in families living with psychogenic nonepileptic seizures (PNES). Using a cohort of patients with epileptic seizures (ES) and their caregivers as controls, we aimed to quantify the level of patient and caregiver stigma in PNES and identify associations of patient and caregiver characteristics with it. METHODS: Patients with PNES and ES and their caregivers completed surveys about demographic, clinical, and psychosocial characteristics. Multivariate regression analysis was used to identify correlates of patient and caregiver stigma. RESULTS: Forty-three patients with PNES and 165 patients with ES were recruited. Compared with patients with ES, patients with PNES had shorter disease duration, higher seizure frequency, normal diagnostic data, poorer psychosocial health, and fewer antiseizure medications (ASMs). A total of 76.5% of patients with PNES and 59.5% of patients with ES felt stigmatized. Patient stigma level was higher in patients with PNES compared with those with ES, and it was negatively associated with patient quality of life (QOL). Additionally, 28 caregivers of patients with PNES and 99 caregivers of patients with ES were recruited. There were no significant demographic, caregiving, or psychosocial differences between the two caregiver cohorts. Seventy-two percent of caregivers of patients with PNES and 47% of caregivers of patients with ES felt stigmatized. Caregiver stigma level was also higher in caregivers of patients with PNES compared with caregivers of patients with ES, and it was negatively associated with patient QOL and positively associated with patient and caregiver anxiety. CONCLUSION: Compared with those with ES, patients and caregivers living with PNES experience stigma more frequently and to a higher extent. Patient QOL emerges as a consistent correlate of that stigma.

Caregiver burden in psychogenic non-epileptic seizures.

OBJECTIVE: Caregiver burden in psychogenic non-epileptic seizures (PNES) is an important but understudied reality. The objective of this exploratory study was to quantify caregiver burden in PNES and to identify the patient and caregiver characteristics associated with it. METHODS: PNES patients and their identified caregivers completed surveys about demographic, disease related and psychosocial characteristics during their Epilepsy Monitoring Unit (EMU) admission. Associations were evaluated using the Zarit Caregiver Burden Inventory (ZCBI) score as an independent variable and the patient and caregiver related characteristics as dependent variables. RESULTS: 43 patients and 28 caregivers were recruited. The patients were on average 36 years old, single women, unemployed, with some college education. They suffered from PNES on average for 8 years, having approximately 20 seizures per month, and were previously maintained on ≥ 2 antiseizure medications. Most caregivers were first degree relatives with a mean age of 43 years, married employed women of higher educational attainment, typically cohabitating with the patients. Caregiver burden was within the mild-moderate range (ZCBI mean score 28). The burden appeared higher in caregivers of male patients. Patient quality of life, depression and medication side effects were associated with that burden. Additionally, caregiver stigma, depression and anxiety emerged as potential contributors. In the multivariate analysis, patient quality of life and caregiver depression stood out as the most robust factors. CONCLUSION: There is substantial caregiver burden in PNES. It is associated with both the patient and the caregiver psychosocial well-being in a reciprocal relationship.

Socioeconomic disparities in patients with psychogenic nonepileptic seizures and their caregivers.

OBJECTIVE: There is no information on disparities of patients with psychogenic nonepileptic seizures (PNES) and their caregivers. The objective of this exploratory study is to compare patients with PNES and caregivers with low socioeconomic status (SES) with those of high SES for disparities in healthcare use, seizures, medication adverse effects, psychosocial impact, and knowledge about epilepsy. METHODS: Patients with PNES and caregivers completed surveys about the aforementioned outcomes during their Epilepsy Monitoring Unit (EMU) admission. Associations were evaluated using SES as a binary independent variable and the patient- and caregiver-related outcomes as dependent variables. RESULTS: Forty-three patients and 28 caregivers were recruited. The majority of patients were on average 36 years old, single women, unemployed, with some college education. The majority had PNES for 8 years averaging 20 seizures per month and were maintained on ≥2 antiepileptic drugs (AEDs) prior to their EMU admission. Most caregivers were first-degree relatives with a mean age of 43 years, married employed women of higher educational attainment, typically cohabitating with the patients. Low SES patients showed poorer knowledge about epilepsy (p < 0.0001) and higher anxiety levels (p = 0.03). Conversely, high SES patients demonstrated poorer social functioning (p = 0.04). High SES caregivers showed higher caregiving burden (p = 0.01). CONCLUSION: There are noteworthy disparities in patients with PNES of different SES and their caregivers. Identification of those disparities is a critical step in the creation of appropriate interventions to address them.

Painted black: Iguana melanoderma (Reptilia, Squamata, Iguanidae) a new melanistic endemic species from Saba and Montserrat islands (Lesser Antilles).

The Lesser Antilles, in the Eastern Caribbean, is inhabited by three Iguana species: the Lesser Antillean iguanaIguana delicatissima, which is endemic to the northernmost islands of the Lesser Antilles, the introduced common iguana from South America, Iguana iguana iguana, represented also by the two newly described endemic subspecies Iguana iguana sanctaluciae from Saint Lucia and Iguana iguana insularis from Saint Vincent and the Grenadines, and Grenada, and the introduced Iguana rhinolopha from Central America. Drawing on both morphological and genetic data, this paper describes the Iguana populations from Saba and Montserrat as a new species, Iguana melanoderma. This species is recognized on the basis of the following combination of characteristics: private microsatellite alleles, unique mitochondrial ND4 haplotypes, a distinctive black spot between the eye and tympanum, a dorsal carpet pattern on juveniles and young adults, a darkening of body coloration with aging (except for the anterior part of the snout), a black dewlap, pink on the jowl, the high number of large tubercular nape scales, fewer than ten medium sized-triangular dewlap spikes, high dorsal spikes, and lack of horns on the snout. This new melanistic taxon is threatened by unsustainable harvesting (including for the pet trade) and both competition and hybridization from escaped or released invasive alien iguanas (I. iguana iguana and I. rhinolopha) from South and Central America, respectively. The authors call for action to conserve Iguana melanoderma in Saba and Montserrat and for further research to investigate its relationship to other melanistic iguanas from the Virgin Islands and coastal islands of Venezuela.

Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin.

After subarachnoid haemorrhage, prolonged exposure to toxic extracellular haemoglobin occurs in the brain. Here, we investigate the role of haemoglobin neurotoxicity in vivo and its prevention. In humans after subarachnoid haemorrhage, haemoglobin in cerebrospinal fluid was associated with neurofilament light chain, a marker of neuronal damage. Most haemoglobin was not complexed with haptoglobin, an endogenous haemoglobin scavenger present at very low concentration in the brain. Exogenously added haptoglobin bound most uncomplexed haemoglobin, in the first 2 weeks after human subarachnoid haemorrhage, indicating a wide therapeutic window. In mice, the behavioural, vascular, cellular and molecular changes seen after human subarachnoid haemorrhage were recapitulated by modelling a single aspect of subarachnoid haemorrhage: prolonged intrathecal exposure to haemoglobin. Haemoglobin-induced behavioural deficits and astrocytic, microglial and synaptic changes were attenuated by haptoglobin. Haptoglobin treatment did not attenuate large-vessel vasospasm, yet improved clinical outcome by restricting diffusion of haemoglobin into the parenchyma and reducing small-vessel vasospasm. In summary, haemoglobin toxicity is of clinical importance and preventable by haptoglobin, independent of large-vessel vasospasm.