A 56-year-old woman with Down syndrome presented with right-sided weakness and dysarthria, and was found on CT/CTA to have a left middle cerebral artery infarct secondary to moyamoya disease. Her left posterior inferior cerebellar artery (PICA) was fed both by the left vertebral artery, and the left ascending pharyngeal artery (APA), with a variant origin from the internal carotid artery (ICA), then passing through the jugular foramen (Figure 1). Her right PICA originated exclusively from her right occipital artery, also via the jugular foramen (Figure 2). The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated from the brachiocephalic trunk. In addition, she had a trifurcated anterior cerebral artery (ACA), and just prior to this trifurcation, her left ACA was partially supplied by the left ICA, via a superior hypophyseal artery. This case is noteworthy for several reasons. First, though it is exceedingly rare to have the PICA supplied by the jugular branch of the APA, this is the first reported case with an ICA origin of that APA.1,2 The fact that both PICAs in this patient originate from the anterior circulation should remind clinicians that in unexplained posterior circulation infarctions, vascular anatomy should be explored, as carotid-vertebrobasilar anastomoses such as these are rare, but possible. Lastly, the conjunction of moyamoya disease and anomalies of the vertebrobasilar system in a patient with Down syndrome raises interesting questions about the influence of trisomy 21 on the developing vasculature. Connections from the APA to the vertebrobasilar system are hypothesized to result from a lack of regression of an embryological anastomosis, in line with the more common persistent trigeminal and persistent hypoglossal arteries.1 Patients with moyamoya disease have a significantly higher rate of persistent carotid-vertebrobasilar anastomoses than the general population,3 and are also 26 times more likely to have Down syndrome.4 Correspondingly, patients with Down syndrome have significantly higher levels of moyamoya disease, and are more than 10 times as likely as the general population to have abnormalities of the Circle of Willis5 and vertebral arteries.6 Several genes on chromosome 21 are known to affect angiogenesis, namely collagen XIII/endostatin (COL18A1), DYRK1A, and Down syndrome candidate region 1 (DSCR1), possibly through inhibition of VEGF activity.7 Whether additional copies of these genes are responsible for the anomalous vascular development seen in Down syndrome, in turn predisposing to the development of moyamoya disease, could benefit from further exploration.

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

Introduction: Acute aortic syndrome (AAS) is a rare clinical syndrome with a high mortality encompassing acute aortic dissection, intramural hematoma and penetrating atherosclerotic ulcer. Up to 38% of cases are misdiagnosed on first presentation. There is a large variation in use of computed tomography to rule out AAS. The Canadian clinical practice guideline for the diagnosis of AAS was developed in order to reduce the frequency of misdiagnoses. As part of the guideline, a clinical decision aid was developed to facilitate clinician decision-making based on practice recommendations. Our objective was to validate the sensitivity of this clinical decision aid. Methods: Our validation cohort was recruited from a retrospective review of all cases of AAS diagnosed at three tertiary care emergency departments and one cardiac referral center from 2002-2019. Inclusion criteria: >18 years old, non-traumatic, symptoms <14 days and AAS confirmed on computed tomography, transesophageal echocardiography, intraoperatively or postmortem. The clinical decision aid assigns an overall score of 0-7 based on high risk pain features, risk factors, physical examination and clinical suspicion. Sensitivity with 95% confidence intervals are reported. Based on a national survey, a miss rate of <1% was predefined for the validation threshold. Results: Data was collected from 2002-2019 yielding 222 cases of AAS (mean age of 65 (SD 14.1) and 66.7% male). Kappa for data abstraction was 0.9. Of the 222 cases of AAS (type A = 125, type B = 95, IMH = 2), 35 (15.7%) were missed on initial assessment. Patients were risk stratified into low (score = 0, 2 (0.9%)) moderate (score = 1, 42 (18.9%)) and high risk (score ≥2,178 (80.2%)) groups. A score ≥1 had a sensitivity of 99.1% (95% CI 96.8-99.9%) in the detection of AAS. The clinical decision aid missed 0.9% (95% CI 0.3-3%) of cases. Conclusion: The Canadian clinical practice guideline's AAS clinical decision aid is a highly sensitive tool that uses readily available clinical information. Although the miss rate was <1%, the 95% confidence intervals crossed the predefined threshold. Further validation is needed in a larger population to ensure the miss rate is below an acceptable level.

Impairment on inhibitory tasks has been well documented in bipolar disorder (BD). Differences in cerebral blood flow (CBF) between BD patients and healthy comparison (HC) participants have also been reported. Few studies have examined the relationship between cognitive performance and regional CBF in this patient population. We hypothesized that group differences on an inhibitory task (the Delis-Kaplan Executive Function Scale’s Color-Word Inhibition task) would be associated with differential CBF in bilateral anterior cingulate cortex (ACC), inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) regions. Whole brain resting CBF was measured using Multiphase Pseudocontinuous Arterial Spin Labeling MR imaging for 28 euthymic BD and 36 HC participants. Total gray matter (GM) CBF was measured, and regional CBF values were extracted for each region of interest (ROI) using Freesurfer-based individual parcellations. Group, CBF, and group-by-CBF interaction were examined as predictors of inhibition performance. Groups did not differ in age, gender or education. BD patients performed significantly worse on Color-Word inhibition. There were no significant group differences in CBF in either total GM or in any ROI. There was a group by CBF interaction in the bilateral ACC, right IPL and right DLPFC such that better inhibitory performance was generally associated with higher resting state CBF in BD subjects, but not HC participants. Although CBF was not abnormal in this euthymic BD sample, results confirm previous reports of inter-episode inhibitory deficits and indicate that the perfusion-cognition relationship is different in BD compared to HC individuals. (JINS, 2015, 21, 105–115)

Background: Inappropriate sexual behavior (ISB) is an important topic in geriatrics; etiologies remain unclear and evidence for the efficacy of treatment strategies is limited. The aims of this study were to provide a description of the phenomenology of ISB in the geriatric population, to identify potential contributing factors, and to review the efficacy of interventions aimed at reducing ISB.

Methods: A retrospective chart review was conducted of ten patients admitted to an academic inpatient geriatric psychiatry ward because of their ISB (study group) and ten patients matched in age and gender (control group). A comprehensive chart review inventory was done to determine variables that may contribute to ISB. For the study group, effectiveness, adverse effects, and discontinuation due to adverse effects of interventions aimed at reducing ISB were reviewed.

Results: A significant finding was the association of a history of right frontal lobe stroke with ISB (Fisher's Exact Probability Test p < 0.05). Also significant was performance on cognitive testing and the presence of dementia (Fisher's Exact Probability Test p < 0.05) in the study group. Citalopram was well tolerated but with minimal reduction of ISB. Atypical antipsychotics olanzapine and risperidone were effective in some cases but also had adverse effects. Medroxyprogesterone acetate was well tolerated and effective in all cases in which it was utilized (n = 5).

Conclusions: This study suggests that ISB in the geriatric population is associated with a history of right frontal lobe stroke and with severity of dementia. Case examples of pharmacologic interventions are reviewed.

Background: The orbitofrontal cortex has been implicated as a key component in depression by several imaging studies. This study aims to examine morphometrically glial cell and neuronal density and neuronal volume in the orbitofrontal cortex of late-life major depression patients.

Methods: Post mortem tissue from 13 patients with major depression and 11 matched controls was obtained and analyzed using the optical disector and nucleator methods.

Results: No changes were found in glial cell, pyramidal or non-pyramidal neuron density, or in non-pyramidal and pyramidal neuron volume in the orbitofrontal cortex.

Conclusions: Based on previous findings, this study suggests variability in morphological changes within the orbitofrontal cortex, as well as the prefrontal cortex as a whole.

Background: Neuroimaging studies have revealed structural and functional changes in brain regions associated with major depressive disorder (MDD). These abnormalities appear to be more common and extensive in patients with late-life depression than in younger patients. It has therefore been hypothesized that different morphometric and pathological changes may be associated with MDD, depending on age.

Methods: This review stratifies the findings of the various studies on cell morphology in MDD according to age and assesses any possible differences in neuronal and glial cell changes in younger and older age groups.

Results: Recent morphological studies in postmortem tissue have revealed alterations in neuron and glial cell populations in the frontal and subcortical circuitry associated with depression. These may differ by age, with glial reduction consistently reported in younger groups in cortical areas and neuronal changes identified in studies with older subjects.

Conclusions: Apparent differences in the morphological changes between younger and elderly patients may suggest a differing pathological basis in MDD, dependent on age.

With light and scanning electron microscopy of vascular corrosion casts, we have observed in Urobatis jamaicensis that the fourth epibranchial arteries do not merge completely with the dorsal aorta. Instead they form a brief anastomosis with a short vessel projecting ventrally from the dorsal aorta and maintain their integrity as separately distinct vessels. Posterior to the anastomosis, the right epibranchial becomes the celiac trunk and left epibranchial becomes the anterior mesenteric artery/posterior intestinal artery. This vascular configuration appears to be unique in elasmobranchs.

Objective: To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD).

Methods: The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status.

Results: One or more NPS were observed in 51% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR = 4.76, p = 0.02), depression (OR = 3.87, p = 0.03), and apathy (OR = 4.48, p = 0.02). Hypertension was associated with increased risk of delusions (OR = 2.34, p = 0.02), anxiety (OR = 4.10, p = 0.002), and agitation/aggression (OR = 2.82, p = 0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health.

Conclusions: Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions.

This article reviews the use of white-matter changes as identified on MRI as a surrogate marker in clinical trials on vascular dementia. As of yet, insufficient evidence is present to implement rating or volumetric assessment of the burden of white-matter changes as surrogate marker in such trials, in view of the limited sensitivity to change of current methods and the high measurement error.

Behavioral and psychological symptoms in dementia (BPSD) are an important aspect of the disorder that are now receiving more attention. The design of the trials in vascular dementia needs to account for these features. The specific area of BPSD in vascular dementia, their assessment, and relationship to the design of trials are considered in this article.

Background and objective Volatile anaesthetic effects on altering tone after blocking nitric oxide synthase, cyclo-oxygenase-prostaglandin synthase and KATP channel pathways are controversial. We examined in isolated guinea pig hearts whether anaesthetics alter bradykinin and 5-hydroxytryptamine-induced effects on coronary flow and percentage oxygen extraction after blocking these pathways.

Methods Before and during exposure to sevo-flurane, halothane or isoflurane, hearts were infused with 10−13–10−8 M bradykinin, or 10−8–10−6 M 5-hydroxytryptamine (serotonin), with either L-NAME, indomethacin, or glibenclamide. Bradykinin or 5-hydroxytryptamine alone increased flow and decreased percentage oxygen extraction in a concentration-dependent manner; these effects were largely blocked by L-NAME (nitro-L-arginine methylester), which also decreased basal flow and increased basal percentage oxygen extraction.

Results The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. Drug-induced increases in flow and decreases in percentage oxygen extraction in the absence or presence of glibenclamide or indomethacin were not altered at either of the two concentrations of anaesthetics.

Conclusions Endothelium-dependent vasodilatation is not affected by blocking prostaglandin release or KATP channels in the intact heart even in the presence of an anaesthetic. However, the diminished responses to vasodilators after nitric oxide synthase inhibition is largely restored or enhanced by anaesthetics.

Background and objective The endovascular treatment of abdominal aortic aneurysms has raised great interest amongst vascular surgeons. The aim of this study was to com pare the postoperative morbidity and mortality rates of endovascular treatment with those of open surgery, from the anaesthesiologist's standpoint.

Methods From January 1997 to June 2000, 425 consecutive patients with abdominal aortic aneurysms were referred for regular surgery. Thirty-nine patients who needed a visceral or renal artery revasculariza-tion, or a nephrectomy were excluded. The remaining 386 patients were studied in a prospective manner. Aneurysms were evaluated with spiral computerized tomography scanning and calibrated aortography. After informed consent, only those patients with a suitable vascular anatomy underwent endovascular treatment (n = 193). All other patients underwent open surgery and are considered as a control group n= 193). Endovascular treatment was performed by a femoral or an iliac retroperitoneal route. All stent-grafts were made to measure using auto-expandable stainless-steel stents covered with a standard polyester prosthetic graft.

Results Six patients in the endovascular treatment group needed to be converted to the open surgical technique (during the same operation) because of rupture of the iliac bifurcation (1 patient), a large en-doleak (2 patients), or technical problems (3 patients).

Conclusion The amount of bleeding and the need for blood products were significantly lower in the endovascular treatment group. Despite the absence of significant differences regarding cardiac complications and mortality, there was a lesser incidence of pneumonia, acute respiratory and renal failure. Patients in the endovascular treatment group spent less time in the intensive care unit and in the Hospital.

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean ±SEM) in both artery (63 ± 8.4% of precontraction, n=9) and vein (60 ± 11%, n=7). The relaxation was enhanced by 10−6 M propofol (artery, 72 a 9.5%, n=9; vein, 81 ± 12%, n=7) but not affected by 10−7, 10−5 and 10−4 M propofol. In the presence of Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10−6 M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10−4 M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28 ± 7.5%, n=8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10−6 M propofol was abolished in both arteries and veins whereas 10−5 and 10−4 M propofol reduced the relaxation in arteries (38 ± 13% at 10−5 M, n=6; 30 ± 11% at 10−4 M, n=6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.