Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.

Stroke is a leading cause of morbidity and mortality worldwide. It inflicts immeasurable suffering on patients and their loved ones and carries an immense social cost. Efforts to mitigate the impact of stroke have focused on identifying therapeutic targets for the prevention and treatment. The gut microbiome represents one such potential target given its multifaceted effects on conditions known to cause and worsen the severity of stroke. Vitamin B12 (VB12) serves as a cofactor for two enzymes, methylmalonyl-CoA synthase and methionine synthase, vital for methionine and nucleotide biosynthesis. VB12 deficiency results in a buildup of metabolic substrates, such as homocysteine, that alter immune homeostasis and contribute to atherosclerotic disorders, including ischemic stroke. In addition to its support of cellular function, VB12 serves as a metabolic cofactor for gut microbes. By shaping microbial communities, VB12 further impacts local and peripheral immunity. Growing evidence suggests that gut dysbiosis-related immune dysfunction induced by VB12 deficiency may potentially contributes to stroke pathogenesis, its severity, and patient outcomes. In this review, we discuss the complex interactions of VB12, gut microbes and the associated metabolites, and immune homeostasis throughout the natural history of ischemic stroke.

Objective To test the hypothesis that patients with deep intracerebral hemorrhage (ICH) would encounter hematoma expansion (HE) more frequently compared to patients with lobar ICH. Methods Patients with ICH with neuroimaging to calculate HE were analyzed from the multicenter Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort. Patients with laboratory coagulopathy or preceding anticoagulant use were excluded to assess relationships of ICH location alone (deep vs lobar) with HE, defined as >33% relative growth. Odds ratios (ORs) and 95% confidence intervals (CIs) for these relationships were estimated with logistic regression. Sensitivity and specificity determined HE thresholds best associated with poor 3-month outcomes (modified Rankin score 4-6) stratified by location. Results There were 1,049 patients with deep and 408 patients with lobar ICH analyzed. Deep ICH locations were more likely to have HE (adjusted OR 1.57, 95% CI 1.08–2.29) after adjustment for age, sex, race, baseline hematoma size, and intraventricular hemorrhage. However, this difference was nonsignificant (adjusted OR 1.35, 95% CI 0.81–2.24) after controlling for time from symptom onset to admission CT in a subgroup analysis of 729 patients with these data. Yet, the threshold of HE best associated with poor outcomes was smaller in deep (30%) compared to lobar (50%) ICH. Conclusions While HE was more frequent in deep than lobar ICH, this could be due to differences in symptom onset to admission CT times in our cohort. However, patients with deep ICH appear particularly vulnerable to the deleterious effects of small volumes of HE. Further studies should clarify whether ICH location needs to be considered in HE treatment paradigms.

Brain injury resulting from sepsis, or sepsis-associated encephalopathy (SAE), occurs due to impaired end-organ perfusion, dysregulated inflammation affecting the central nervous system (CNS), blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, accumulation of toxic neuropeptides and impaired toxin clearance secondary to sepsis-induced hepatic and renal dysfunction. The gut microbiome becomes pathologically altered in sepsis, which likely contributes to the pathogenesis of SAE. Herein, we review the literature detailing dysregulation of microbiota-gut-brain axis (MGBA) in SAE and highlight potential therapeutic strategies to modulate the gut microbiome to mitigate sepsis-induced brain injury.

Background and Purpose: Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke. Methods: We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors. Results: Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15–1.19]) and functional (1.16 [95% CI, 1.15–1.17]), inflammatory (1.13 [95% CI, 1.12–1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12–1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94–1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94–1.00]). Conclusions: In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

Background: Traumatic extracranial internal carotid artery (ICA) dissections are uncommon and can be difficult to treat. Thinning of adventitia and dilatation may occur following arterial dissection, thus resulting in a fusiform pseudoaneurysm, which can subsequently cause bleeding, expanding, or pulsatile hematoma. Currently, medical management with anticoagulation remains the first line of treatment and yields good outcomes in 75% of cases with a mortality rate of 3-4%. Endovascular intervention is indicated with failure of medical therapy, progressive enlargement of a traumatic pseudoaneurysm, acute flow-related infarcts due to vessel occlusion, or when anticoagulation is contraindicated due to risk of pseudoaneurysm rupture and hemorrhage. Recognized interventional treatments include parent artery occlusion with or without revascularization, endovascular coil embolization, and covered stenting. Summary: A wide variety of endovascular stents are available that are capable of opening a stenosed vessel while obliterating the associated false lumen and providing a scaffold for embolization of the pseudoaneurysm. The use of the Pipeline Embolization Device (PED) in the management of traumatic intracranial pseudoaneurysms has been described. However, there are few reports on the usage of the PED for treating traumatic extracranial ICA dissection and/or pseudoaneurysms. However, a potential complication of the use of PED in the extracranial ICA is a hypothetical tendency to migrate in a mobile vessel. Thus, the risk of migration of the PED has encouraged practitioners to adopt strategies to limit this risk. Key Messages: We describe different techniques employed to anchor the flow-diverting construct within tortuous, mobile vessels.