Cerebrovascular Lesions Research Articles

Post-stroke mania

IntroductionApproximately one-third of stroke survivors develop poststroke depression. Post-stroke mania is relatively rare, with a prevalence of less than 2%. One review of case reports of late-onset mania in 2015 demonstrated that 51% of the patients had established vascular risk factors. In 28% of cases, the treatment of underlying organic cause contributed to successful remission of the manic episode.ObjectivesFor this review, we aimed to compile published case reports from the past 20 years to review late-onset mania as one of the neuropsychiatric outcomes of stroke and its management.Methodsliterature search on Pubmed, PsychInfo, and Embase utilizing keywords combinations: Bipolar, Manic, Mania, Secondary, Stroke, Poststroke, Post-stroke, Elderly, Old, Late onset, Late-onset, Lateonset, Hemisphere, Brain, Vascular, Infarction.ResultsAmong the 17 case reports, the age of onset of manic episode ranged from 47 to 86 with a mean of 67 years. Of the 17 cases, the right hemisphere was the most frequently affected (14/17, 82%), with cerebrovascular lesion involving the left hemisphere in 3 cases (17.6%).ConclusionsClinicians should consider mania secondary to an organic cause in patients presenting with focal or soft neurological signs or symptoms, manic episode with atypical symptoms such as visual or olfactory hallucinations, altered mental status, disorientation, impairment in memory or cognition, unusual age of onset for bipolar disorder, or unusual illness course such as single episode of mania or poor response to psychopharmacologic treatment. Some reviews suggest combination of mood stabilizers and second-generation antipsychotics. Benzodiazepines recommended as an adjunctive drug for acute management such as agitation, aggressive behavior or disinhibition.DisclosureNo significant relationships.

The effect of selective hypothermia of the cerebral cortex on metabolism in patients with prolonged impairment of consciousness

BACKGROUND: Selective craniocerebral hypothermia, used in the acute period of brain damage, ensures the development of positive clinical effects (rapid and persistent reduction of neurological deficit, increased consciousness, and maintenance of normothermy in feverish patients). The safety and efficacy of craniocerebral hypothermia in the acute period of cerebrovascular lesions prompted the use of craniocerebral cooling in patients with chronic disorders of consciousness. For this category of patients, the craniocerebral hypothermia technique has been developed, which requires careful study including its effect on overall metabolism.
 AIMS: To determine the nature of the metabolic response to craniocerebral hypothermia procedures in patients in a vegetative state and minimal conscious state.
 MATERIALS AND METHODS: A pilot study was conducted from February 3, 2021 until March 3, 2022. This study included 34 patients who were in a state of chronic disorders of consciousness, CRS-R score of 8 (vegetative state and minimally conscious state), after severe brain damage (stroke, 25; brain injury, 5; anoxic brain injuries, 4). Hypothermia was induced using the ATG-01 device, lowering the temperature of the scalp to 47C with a cooling procedure lasting for 120 min. The indirect calorimetry method was conducted before cooling and after 105 min of the craniocerebral hypothermia session. Statistical analysis was performed using the program StatTech v. 2.6.5 (StarTech LLC, Russia).
 RESULTS: Craniocerebral cooling provided a decrease in the temperature of the frontal cortex of the large hemispheres already after 30 min from 36.4C to 34.90.41C in the left hemisphere and 34.70.47C in the right hemisphere. By the 120th minute, the temperature in the left hemisphere reached 34.00.40C, and that in the right hemisphere reached 33.30.51C, decreasing by 2.4C and 3.1C, respectively. Subsequently, 30 min after the completion of craniocerebral hypothermia, the brain temperature remained lowered by 0.7C. Changes in the level of metabolism under the influence of craniocerebral hypothermia were of a multidirectional nature. In 24 patients (70.59%), the resting energy expenditure (REE) index increased to varying degrees by the end of the cooling procedure, and in 10 participants, it decreased. A significant spread of data allowed only a descriptive analysis of the results obtained during a 120-min craniocerebral hypothermia session.
 CONCLUSIONS: Chronic disorders of consciousness are largely associated with severe damage of the cerebral cortex. It can be assumed that in patients who reacted with a decrease in REE to the induction of hypothermia, at least metabolic activity in the intact parts of the cerebral cortex was preserved to a certain extent, which may indicate some level of rehabilitation potential. The lack of expression of the reactions of the general metabolism to craniocerebral cooling may be due to the fact that the severe damage to the cerebral cortex excluded the selectivity of hypothermic exposure.

Frontotemporal neurofibrillary tangles and cerebrovascular lesions are associated with autism spectrum behaviors in late-life dementia.

The pathologic substrates or neuroanatomic regions responsible for similarities in behavioral features seen in autism spectrum disorder and late-life dementia remain unknown. The present study examined the neuropathologic features of late-life dementia in research volunteers with and without antemortem behaviors characteristic of autism spectrum disorders. Antemortem cross-sectional assessment of autistic spectrum behaviors proximal to death in persons with diagnosis of mild cognitive impairment or dementia was completed using the Gilliam Autism Rating Scale, 2nd edition (GARS-2), followed by postmortem quantitative and semiquantitative neuropathologic assessment. All individuals who completed the GARS-2 prior to autopsy were included (n = 56) and we note that no participants had known diagnosis of autism spectrum disorder. The GARS-2 was used as an antemortem screening tool to stratify participants into two groups: "Autism Possible/Very Likely" or "Autism Unlikely." Data were analyzed using nonparametric statistics comparing location and scale to evaluate between-group differences in pathologic features. Neurofibrillary tangles (NFT; p = 0.028) density and tau burden (p = 0.032) in the frontal region, the NFT density (p = 0.048) and neuritic plaque burden (p = 0.042), and the tau burden (p = 0.032) of the temporal region, were significantly different in scale between groups. For measures with significant group differences, the medians of the Autism Possible/Very Likely group were roughly equal to the 75th percentile of the Autism Unlikely group (i.e., the distributions were shifted to the right). This study links behaviors characteristic of autism to increased pathologic tau burden in the frontal and temporal lobes in persons with late-life dementia. Additional studies are needed to determine causal factors and treatment options for behaviors characteristic of autism behaviors in late-life dementias.

Can CHA2DS2-VASc and HAS-BLED Foresee the Presence of Cerebral Microbleeds, Lacunar and Non-Lacunar Infarcts in Elderly Patients With Atrial Fibrillation? Data From Strat-AF Study.

Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic risk. In this context, validity of congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke, vascular disease, age 65–74 years and sex category (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS–BLED) scales, used to respectively evaluate thrombotic and hemorrhagic risks, is incomplete. In patients with AF, brain MRI has led to the increased detection of “asymptomatic” brain changes, particularly those related to small vessel disease, which also represent the pathologic substrate of intracranial hemorrhage, and silent brain infarcts, which are considered risk factors for ischemic stroke. Routine brain MRI in asymptomatic patients with AF is not yet recommended. Our aim was to test predictive ability of risk stratification scales on the presence of cerebral microbleeds, lacunar, and non-lacunar infarcts in 170 elderly patients with AF on oral anticoagulants. Ad hoc developed R algorithms were used to evaluate CHA2DS2-VASc and HAS–BLED sensitivity and specificity on the prediction of cerebrovascular lesions: (1) Maintaining original items' weights; (2) augmenting weights' range; (3) adding cognitive, motor, and depressive scores. Accuracy was poor for each outcome considering both scales either in phase 1 or phase 2. Accuracy was never improved by the addition of cognitive scores. The addition of motor and depressive scores to CHA2DS2-VASc improved accuracy for non-lacunar infarcts (sensitivity = 0.70, specificity = 0.85), and sensitivity for lacunar–infarcts (sensitivity = 0.74, specificity = 0.61). Our results are a very first step toward the attempt to identify those elderly patients with AF who would benefit most from brain MRI in risk stratification.

NOGOB receptor deficiency increases cerebrovascular permeability and hemorrhage via impairing histone acetylation-mediated CCM1/2 expression.

The loss function of cerebral cavernous malformation (CCM) genes leads to most CCM lesions characterized by enlarged leaking vascular lesions in the brain. Although we previously showed that NOGOB receptor (NGBR) knockout in endothelial cells (ECs) results in cerebrovascular lesions in the mouse embryo, the molecular mechanism by which NGBR regulates CCM1/2 expression has not been elucidated. Here, we show that genetic depletion of Ngbr in ECs at both postnatal and adult stages results in CCM1/2 expression deficiency and cerebrovascular lesions such as enlarged vessels, blood-brain-barrier hyperpermeability, and cerebral hemorrhage. To reveal the molecular mechanism, we used RNA-sequencing analysis to examine changes in the transcriptome. Surprisingly, we found that the acetyltransferase HBO1 and histone acetylation were downregulated in NGBR-deficient ECs. The mechanistic studies elucidated that NGBR is required for maintaining the expression of CCM1/2 in ECs via HBO1-mediated histone acetylation. ChIP-qPCR data further demonstrated that loss of NGBR impairs the binding of HBO1 and acetylated histone H4K5 and H4K12 on the promotor of the CCM1 and CCM2 genes. Our findings on epigenetic regulation of CCM1 and CCM2 that is modulated by NGBR and HBO1-mediated histone H4 acetylation provide a perspective on the pathogenesis of sporadic CCMs.

Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men

Background: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. Methods: Participants were community-dwelling men (40–79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. Results: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 μmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67–0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. Conclusions: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

Transarterial Embolization of Ethmoidal Dural Arteriovenous Fistula: 2-Dimensional Video.

Cranial dural arteriovenous fistulae (dAVF) are rare cerebrovascular lesions characterized by direct arteriovenous shunting within the dural leaflets, with stark heterogeneity in angioarchitecture among different patients.1,2 It is, therefore, crucial to personalize treatment strategies to unique patients and their specific lesion. The authors describe an ethmoidal dAVF in an elderly female patient with arterial supply from the ophthalmic arteries and the contralateral middle meningeal artery. This, together with recent advances in microcatheter technology and the controllability of modern liquid embolic agents, opened up a route for transarterial embolization, obviating the need to course through the ophthalmic artery or the need for open surgery.3 Onyx is Food and Drug Administration-approved for treatment of arteriovenous malformations and can be used off-label for treatment of dAVF, as described here. This video demonstrates the technical nuances and safety considerations of transarterial liquid embolization through the middle meningeal artery while providing an overview of alternative treatment approaches for ethmoidal dAVFs. The patient consented to the procedure.

Triple bypass for multisystem smooth muscle dysfunction syndrome due to Arg179His ACTA2 mutation

Missense mutations in the smooth muscle-specific isoform of the alpha-actin (ACTA2) gene, which encodes smooth muscle actin, congenitally cause systemic smooth muscle dysfunction, leading to multiple systemic smooth muscle dysfunction syndrome. This disease is often diagnosed through the development of congenital mydriasis, patent ductus arteriosus, or thoracic aortic aneurysm at a young age. Some patients develop cerebrovascular lesions, also known as ACTA2 cerebral arteriopathy, which cause ischemic stroke and require surgical revascularization. However, an effective and safe treatment has not yet been established owing to the rarity of the disease. Furthermore, most reports of this disease involve children, with only a few reports on adults and few detailed reports on treatment outcomes published to date. We report a 46-year-old woman with ACTA2 cerebral arteriopathy caused by Arg179His, the most common mutation in this disease; she is the oldest patient reported with this disease to the best of our knowledge. The patient was diagnosed with multiple systemic smooth muscle dysfunction syndrome and ACTA2 cerebral arteriopathy after experiencing a stroke in the right cingulate gyrus. She underwent direct triple bypass with three anastomoses of the right superficial temporal artery to the middle and anterior cerebral arteries. She developed an ischemic stroke as a postoperative complication.The efficacy and safety of this procedure have not been clearly confirmed owing to the frailty of the donor superficial temporal artery and the poor development of collateral circulation; however, direct bypass should be considered a treatment option for patients experiencing progressive multiple strokes.

Disentangling the Relationship Between Chronic Kidney Disease and Cognitive Disorders.

Chronic kidney disease (CKD) is a rapidly rising global health burden that affects nearly 40% of older adults. Epidemiologic data suggest that individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia, and thus represent a vulnerable population. It is currently unknown to what extent this risk may be attributable to a clustering of traditional risk factors such as hypertension and diabetes mellitus leading to a high prevalence of both symptomatic and subclinical ischaemic cerebrovascular lesions, or whether other potential mechanisms, including direct neuronal injury by uraemic toxins or dialysis-specific factors could also be involved. These knowledge gaps may lead to suboptimal prevention and treatment strategies being implemented in this group. In this review, we explore the mechanisms of susceptibility and risk in the relationship between CKD and cognitive disorders.

Gastrointestinal Microbiome and Neurologic Injury.

Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual. Microbes release short-chain fatty acids (SCFAs) that regulate G-protein-coupled receptors to mediate hormone release, neurotransmitter release (i.e., serotonin, dopamine, noradrenaline, γ-aminobutyric acid (GABA), acetylcholine, and histamine), and regulate inflammation and mood. Further gaseous factors (i.e., nitric oxide) are important in regulating inflammation and have a response in injury. Neurologic injuries such as ischemic stroke, spinal cord injury, traumatic brain injury, and hemorrhagic cerebrovascular lesions can all lead to gut dysbiosis. Additionally, unfavorable alterations in the composition of the microbiota may be associated with increased risk for these neurologic injuries due to increased proinflammatory molecules and clotting factors. Interventions such as probiotics, fecal microbiota transplantation, and oral SCFAs have been shown to stabilize and improve the composition of the microbiome. However, the effect this has on neurologic injury prevention and recovery has not been studied extensively. The purpose of this review is to elaborate on the complex relationship between the nervous system and the microbiome and to report how neurologic injury modulates the status of the microbiome. Finally, we will propose various interventions that may be beneficial in the recovery from neurologic injury.

Current status of augmented reality in cerebrovascular surgery: a systematic review.

Augmented reality (AR) is an adjuvant tool in neuronavigation to improve spatial and anatomic understanding. The present review aims to describe the current status of intraoperative AR for the treatment of cerebrovascular pathology. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following databases were searched: PubMed, Science Direct, Web of Science, and EMBASE up to December, 2020. The search strategy consisted of "augmented reality," "AR," "cerebrovascular," "navigation," "neurovascular," "neurosurgery," and "endovascular" in both AND and OR combinations. Studies included were original research articles with intraoperative application. The manuscripts were thoroughly examined for study design, outcomes, and results. Sixteen studies were identified describing the use of intraoperative AR in the treatment of cerebrovascular pathology. A total of 172 patients were treated for 190 cerebrovascular lesions using intraoperative AR. The most common treated pathology was intracranial aneurysms. Most studies were cases and there was only a case-control study. A head-up display system in the microscope was the most common AR display. AR was found to be useful for tailoring the craniotomy, dura opening, and proper identification of donor and recipient vessels in vascular bypass. Most AR systems were unable to account for tissue deformation. This systematic review suggests that intraoperative AR is becoming a promising and feasible adjunct in the treatment of cerebrovascular pathology. It has been found to be a useful tool in the preoperative planning and intraoperative guidance. However, its clinical benefits remain to be seen.

Motoric Cognitive Risk Syndrome: Symptoms, Pathology, Diagnosis, and Recovery.

The motoric cognitive risk (MCR) syndrome is a pre-dementia condition, marked by the enhanced risk for Alzheimer's disease (AD) and vascular dementia, together with falls, disability, and abnormal movements. The research studies revealed the distinct neurological and non-neurological clinical gait irregularities during dementia and accelerated functional decline, such as postural and balance impairments, memory loss, cognitive failure, and metabolic dysfunctions. The disabling characteristics of MCR comprise altered afferent sensory and efferent motor responses, together with disrupted visual, vestibular, and proprioceptive components. The pathological basis of MCR relates with the frontal lacunar infarcts, white matter hyperintensity (WMH), gray matter atrophy in the pre-motor and pre-frontal cortex, abnormal cholinergic functioning, inflammatory responses, and genetic factors. Further, cerebrovascular lesions and cardiovascular disorders exacerbate the disease pathology. The diagnosis of MCR is carried out through neuropsychological tests, biomarker assays, imaging studies, questionnaire-based evaluation, and motor function tests, including walking speed, dual-task gait tests, and ambulation ability. Recovery from MCR may include cognitive, physical, and social activities, exercise, diet, nutritional supplements, symptomatic drug treatment, and lifestyle habits that restrict the disease progression. Psychotherapeutic counseling, anti-depressants, and vitamins may support motor and cognitive improvement, primarily through the restorative pathways. However, an in-depth understanding of the association of immobility, dementia, and cognitive stress with MCR requires additional clinical and pre-clinical studies. They may have a significant contribution in reducing MCR syndrome and the risk for dementia. Overall, the current review informs the vital connection between gait performance and cognition in MCR and highlights the usefulness of future research in the discernment and treatment of dementiating illness.

Abstract WMP76: Nogo-B Receptor Is Essential For Preserving HBO1-mediated Histone Acetylation In Brain Endothelial Cells And Preventing Cerebrovascular Hemorrhage

Cerebral cavernous malformations (CCMs) are enlarged leaking vascular lesions in the brain caused by loss-of-function mutations in CCM1/2/3 genes or loss of expression. Although we previously showed that Nogo-B receptor (NgBR) knockout in endothelial cells (ECs) results in CCMs-like cerebrovascular lesions in the mouse embryo, the molecular mechanism by which NgBR regulates CCM1/2 expression has not been elucidated. Here, we show that temporal genetic depletion of NgBR in ECs at both the postnatal and adult stages results in CCM1/2 expression deficiency and consequently CCMs-like lesions such as enlarged vessels, blood-brain barrier (BBB) hyperpermeability, and intracerebral hemorrhage. These cerebrovascular defects in the brain of NgBR endothelial-specific knockout (ecKO) mice can be rescued by adeno-associated virus (AAV)-mediated overexpression of CCM1 and CCM2 genes. To reveal the molecular mechanism, we used RNA-seq analysis to examine changes in the transcriptome. Surprisingly, we found that acetyltransferase HBO1 was downregulated in NgBR deficient ECs. The mechanistic study elucidated that NgBR is required for maintaining the expression of CCM1/2 in ECs via HBO1-mediated histone acetylation. ChIP-qPCR data further demonstrated that loss of NgBR impairs the binding of both the HBO1 and acetylated H4K5/K12 at the promoter of CCM1 and CCM2 genes. Similarly, AAV-mediated overexpression of HBO1 restores the acetylation of H4K5/K12 and rescues the CCMs-like cerebrovascular defects in the brain of NgBR ecKO mice. Our findings on epigenetic regulation of CCM1 and CCM2 provide a perspective that NgBR and HBO1-mediated histone H4 acetylation may be targeted for preventing the onset of CCMs-like cerebrovascular disease.

The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson's disease dementia.

Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications. A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage. Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age-matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%-48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD. The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes.

Cerebrovascular disease lesions are additive and tied to vascular risk factors and cognitive impairment.

Cerebrovascular lesions are prevalent in late life and frequently co-occur but the relationship to cognitive impairment is complicated by the lack of consensus around which lesions represent hallmark pathologies for vascular impairment, particularly in the presence of Alzheimer's disease (AD). We developed an easily applicable model of cerebrovascular disease (CVD), defined as the presence of two or more lesions: moderate to severe cerebral amyloid angiopathy, moderate to severe arteriolosclerosis, infarcts (large, lacunar, or micro), and/or hemorrhages. AD was defined as intermediate or high AD neuropathologic change. The contribution of vascular risk factors such as atherosclerosis and/or a health history of heart disease, hyperlipidemia, stroke events, diabetes, or hypertension was also assessed. Logistic regression analysis reported the association of CVD with increasing age, vascular risk factors, AD, and cognitive impairment in this study of 1,485 autopsied individuals. Cerebrovascular lesions were present in 48% and 16% had CVD. Increasing age associated with all lesions (p<0.001), except hemorrhages (p=0.41). CVD was more likely in individuals with vascular risk factors or AD (p<0.01). CVD, but not individual cerebrovascular lesions, associated with impairment in cases without AD (p<0.01), but not in cases with AD (p>0.61). From this, we conclude that a simple, additive model of CVD is 1) age and AD-associated, 2) is associated with vascular risk factors, and 3) clinically correlates with cognitive decline independent of AD.

Double-barrel STA-MCA bypass and partial trapping of a ruptured mycotic MCA aneurysm with flash fluorescence technique.

Mycotic brain aneurysms are rare and unusual cerebrovascular lesions arising from septic emboli that degrade the elastic lamina and vessel wall of intracranial arteries, which results in pathologic dilatation. Mycotic aneurysms are nonsaccular lesions that are not often suitable for clipping and instead require bypass, trapping, and flow reversal. This case demonstrates the use of indocyanine green “flash fluorescence” to identify the cortical distribution supplied by an aneurysm’s outflow, facilitating safe treatment with a double-barrel extracranial-intracranial bypass and partial trapping and conversion of a deep bypass to a superficial one.The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21163

Anatomical Variability in the Origin, Length and Termination of Basilar Artery and its Clinical Implications

Introduction: Basilar artery is one of the frequent locations for cerebrovascular lesions like aneurysm, thrombosis and haemorrhage. Hence,an intricate knowledge of its variant anatomy is essential for diagnostic procedures like Computed Tomography (CT) brain and Magnetic Resonance (MR) angiography. An accurate interpretation of the arterial pattern will help in performing surgeries of brain stem precisely. Any misinterpretation of arterial pattern may affect the diagnosis, treatment and prognosis of the disease. Aim: To elucidate the anatomical variability in the origin, length and termination of basilar artery. Materials and Methods: This cross-sectional study was conducted from May 2019 to April 2020, on 100 human cadaveric brain specimens available in the Department of Anatomy at Government Medical College Pudukkottai, Tamil Nadu, India. The morphology of the basilar artery was studied with respect to the level of the origin, length, level and mode of termination of the basilar artery. Results: Among the 100 human cadaveric brain specimens dissected and examined (mean age of 63.4 years), the mean length of basilar arteries was 2.792±0.32 cm. In all 100 specimens, the basilar artery was formed by the union of right and left vertebral arteries. The basilar artery was found to originate at the level of pontomedullary junction in 84%, below the pontomedullary junction in 14% and above the pontomedullary junction in 2% of specimens. The termination of basilar artery was at the level of upper border of pons in 90%, below the upper border of pons in 7% and above in the interpeduncular fossa in 3% of specimens. The mode of termination was 'V’ shaped in 83%, 'T' shaped in 10%, trifurcation in 3%, quadrifurcation in 3% and pentafurcation in 1% of specimens. Fenestration of basilar artery was seen in 1%. Other variations of basilar artery like duplication were not detected. Conclusion: The level and mode of origin and termination of basilar artery are important with regard to surgical procedures in the lower basilar region. Variations in the basilar artery should be identified preoperatively so that neurosurgeons can modify the surgical approaches.

Pathomechanisms of Vascular Depression in Older Adults.

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto–limbic and other important neuronal networks, may contribute to the development of LLD. The “vascular depression” hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

Recent update on the heterogeneity of the Alzheimer's disease spectrum.

Alzheimer's disease (AD), the most common form of dementia worldwide, is a mixed proteinopathy (β-amyloid, tau and other proteins). Classically defined as a clinicopathological entity, AD is a heterogeneous, multifactorial disorder with various pathobiological subtypes showing different forms of cognitive presentation, currently referred to as the Alzheimer spectrum or continuum. Its morphological hallmarks are extracellular β-amyloid (amyloid plaques) and intraneuronal tau aggregates forming neurofibrillary tangles and neurites, vascular amyloid deposits (cerebral amyloid angiopathy), synapse and neuronal loss as well as neuroinflammation and reactive astrogliosis, leading to cerebral atrophy and progressive mental/cognitive impairment (dementia). In addition to "classical" AD, several subtypes with characteristic regional patterns of tau pathology have been segregated that are characterized by distinct clinical features, differences in age, sex distribution, disease duration, cognitive status, APOE genotype, and biomarker levels. In addition to four major subtypes based on the distribution of tau pathology and brain atrophy (typical, limbic predominant, hippocampal sparing, and minimal atrophy), several other clinical variants (non-amnestic, corticobasal, behavioral/dysexecutive, posterior cortical variants, etc.) have been identified. These heterogeneous AD variants are characterized by different patterns of key neuronal network destructions, in particular the default-mode network that is responsible for cognitive decline. Other frequent age-related co-pathologies, e.g., cerebrovascular lesions, Lewy and TDP-43 pathologies, hippocampal sclerosis, or argyrophilic grain disease, essentially influence the clinical picture and course of AD, and can challenge our understanding of this disorder including the threshold and causal relevance of each individual pathology. Unravelling the clinico-morphological heterogeneity among the AD spectrum entities is important for better elucidation of the pathogenic mechanisms affecting the aging brain that may enable a broader diagnostic coverage of AD as a basis for implementing precision medicine approaches and for developing preventive and ultimately disease-modifying therapies for this devastating disorder.

Antemortem visit‐to‐visit blood pressure variability predicts cerebrovascular lesion burden in autopsy‐confirmed Alzheimer’s disease

Blood pressure variability is a risk factor for stroke, cognitive impairment and Alzheimer's dementia, but the underlying neuropathological mechanisms remain understudied. Large blood pressure fluctuations may stress arterial walls and promote vascular-endothelial injury, increasing risk for cerebrovascular disease. Several studies link elevated blood pressure variability to MRI-based markers of cerebrovascular lesions, but less is known about relationships with specific cerebrovascular or Alzheimer's pathologies at autopsy. The aim of the current study was to determine whether antemortem blood pressure variability predicts cerebrovascular and Alzheimer's pathology in autopsy-confirmed Alzheimer's disease. 513 older adults from the National Alzheimer's Coordinating Center study underwent repeated annual blood pressure measurement and were confirmed to have Alzheimer's disease at postmortem evaluation. Visit-to-visit blood pressure variability was calculated over a 3-4 year follow-up period. Multiple linear regression examined relationships between blood pressure variability and an index of overall cerebrovascular lesion burden and Braak & Braak stage. Ordinal logistic regression examined relationships with other specific cerebrovascular and Alzheimer's neuropathological features. All analyses covaried for age, sex, years of education, body mass index, Mini Mental State Examination score, years from first blood pressure measurement to death, antihypertensive medication use and average blood pressure. Elevated blood pressure variability predicted increased postmortem cerebrovascular lesion burden (ß = .26 [.11, .42]; p = .001; R2 = .12). Increased blood pressure variability predicted specific cerebrovascular lesion severity, including atherosclerosis in the Circle of Willis (OR = 1.21 [1.02, 1.43]; p = .03) and cerebral arteriolosclerosis (OR = 1.30 [1.06, 1.61]; p = .01). No significant relationships were observed between blood pressure variability and Alzheimer's disease pathological findings, including Braak & Braak stage, neuritic plaques or diffuse plaques. Findings suggest that elevated blood pressure variability is related to postmortem cerebrovascular lesion burden in autopsy-confirmed Alzheimer's disease, independent of average blood pressure and Alzheimer's disease neuropathology. Blood pressure fluctuation may selectively promote atherosclerotic and arteriolosclerotic brain lesions with potential implications for cognitive impairment and dementia.