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Purpose To present select cases of paracentral acute middle maculopathy (PAMM) demonstrating progressive vascular occlusion and the ischemic cascade, and illustrate scenarios in which therapeutic intervention may be considered. Design Perspective. Methods Review and interpretation of selected literature, with perspective on the evaluation and management of patients with PAMM lesions. Multimodal imaging, including cross sectional and en face optical coherence tomography (OCT), of three illustrative cases of PAMM are presented, with progressive vascular occlusion and evidence of the ischemic cascade noted in two of the cases. Results All three cases showed evidence of PAMM at baseline, including perivenular PAMM in two of the cases. Progression from a mild central retinal vein occlusion (CRVO) to a more severe CRVO was noted in the first case, while the second case progressed from an incomplete to complete central retinal artery occlusion. In the third case, there was resolution of PAMM lesions associated with partial CRAO after the patient was started on aspirin. Conclusions Perivenular PAMM can be the only presenting sign of retinal vascular occlusion. In such cases it is important to differentiate between partial CRVO and incomplete CRAO as the underlying cause. This Perspective provides guidance on making this important distinction, which plays a critical role in directing the nature and urgency of the systemic work up. In patients with PAMM caused by partial retinal arterial occlusion, a benign empirical approach such as low-dose aspirin (81 mg) may be reasonable to reduce the likelihood of subsequent vision loss from progression to complete arterial occlusion. A clinical trial, however, is necessary to support such a strategy.

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra‐arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra‐arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L‐type calcium channels, whereas lubeluzole, an N‐methyl‐D‐aspartate modulator, works in a delayed fashion blocking intracellular glutamate trafficking. We hypothesized that combination therapy would provide complimentary and potentially synergistic benefit treating brain tissue undergoing various stages of injury. Physiological measurements for heart rate and pulse distention (blood pressure) demonstrated no detrimental effects between groups, suggesting that the combination drug administration is safe. Tissue analysis demonstrated a significant difference between combination and control (saline) groups in infarct volume, neuronal health, and astrogliosis. Although a significant difference in functional outcome was not observed, we did note that the combination treatment group had a greater percent change from baseline in forced motor movement as compared with controls. This study demonstrates the safety and feasibility of intra‐arterial combination therapy following successful recanalization and warrants further study.

Introduction.The prevalence of cerebral vascular diseases is steadily increasing worldwide. Cerebral stroke represents the most serious of them, being one of the leading causes of mortality and disability of the population. Reduction of morbidity and mortality from stroke can be achieved by improving preventive measures aimed at the correction of risk factors. The review presents domestic and foreign literature data on the risk factors of ischemic stroke and the system of primary prevention of acute ischemic brain lesions.Materials and methods.Data from eLibrary, MedLine, Scopus, Springerlink, and the scientific electronic library «Cyberleninka» were analyzed.Results and Discussion.The authors give an overview of pathological conditions that can lead to the development of cerebral vascular accident. Methods of primary prevention of ischemic stroke are considered in accordance with the European guidelines on stroke management. Current views on the correction of modifiable risk factors (arterial hypertension, diabetes mellitus, hyperlipidemia, heart and vascular pathology, etc.) are presented. Recommendations on lifestyle and body weight reduction are given. In addition to the well-known information, the authors present the data of new studies on the role of vitamin D in the ischemic cascade and consider the possible pathogenetic mechanisms of this effect. The review also provides information on the association of vitamin D deficiency with other pathological conditions that are the causes of ischemic stroke and the effect of vitamin D on the volume of ischemic lesions, the severity of the outcome and the risks of repeated vascular accidents.Conclusion.The study of risk factors for ischemic stroke and the development of primary prevention methods is one of the priority areas of modern neurology, since it will improve the system of care for patients with cerebrovascular disease.

Stroke is the second, and in some countries the third cause of mortality in the population and one of the causes of disability in the adult population. According to statistics, in 2018, 15 million cases of stroke and 6 million deaths were diagnosed,The only currently approved treatments for acute stroke are intravenous tissue plasminogen activator (rtPA) and intra-arterial thrombectomy, which are used in less than 10% and 1% of patients, respectively.The literature review is devoted to the pathophysiology and molecular mechanisms of damage in cerebral ischemia. The modern concept of two strategies of cell therapy is discussed: neuroprotection and remodeling; the role of stem cells in reducing local and systemic inflammation, neurogenesis and angiogenesis, increasing neuronal plasticity, and protecting the blood-brain barrier, the role of paracrine factors and extracellular vesicles is shown.Methods of stem cell delivery are described: direct intracerebral transplantation, intraventricular and intrathecal, intravenous and intraarterial; the number of cells, their type and optimal delivery time depending on the acute, subacute and chronic periods of stroke. We also described recently designed the radially branched deployment (RBD) device and Cleveland multiport catheter for convection-enhanced delivery in which a cell-delivery catheter can be deployed at various angles and depths from a single longitudinal cannula. Finally, data on the completed 15 clinical trials from 2015 to the present, in which 513 patients took part, are presented. A detailed analysis of the efficacy and safety of cell therapy has been carried out.

Stroke is a leading cause of death and disability worldwide. Several mechanisms are involved in the pathogenesis of ischemic stroke (IS). The contributory role of the inflammatory and immunity processes was demonstrated both in vitro and in animal models, and was confirmed in humans. IS evokes an immediate inflammatory response that involves complex cellular and molecular mechanisms. All components of the innate and adaptive immunity systems are involved in several steps of the ischemic cascade. In the early phase, inflammatory and immune mechanisms contribute to the brain tissue damage, whereas, in the late phase, they participate to the tissue repair processes. In particular, damage-associated molecular patterns (DAMPs) appear critical for the promotion of altered blood brain barrier permeability, leukocytes infiltration, tissue edema and brain injury. Conversely, the activation of regulatory T lymphocytes (Tregs) plays protective effects. The identification of specific cellular/molecular elements belonging to the inflammatory and immune responses, contributing to the brain ischemic injury and tissue remodeling, offers the advantage to design adequate therapeutic strategies. In this article, we will present an overview of the knowledge on inflammatory and immunity processes in IS, with a particular focus on the role of DAMPs and leukocytes infiltration. We will discuss evidence obtained in preclinical models of IS and in humans. The main molecular mechanisms useful for the development of novel therapeutic approaches will be highlighted. The translation of experimental findings to the human disease is still a difficult step to pursue. Further investigations are required to fill up the existing gaps.

Обзор посвящен рассмотрению современных подходов к фармакологической модуляции структурно-функционального состояния митохондриального аппарата нейронов как перспективной стратегии терапии ишемического инсульта головного мозга, составляющего по современным оценкам до 85% всех случаев острого нарушения мозгового кровообращения. В обзоре проведен анализ классических представлений о нейропротекции как терапии, направленной на блокирование ключевых патогенетических звеньев «ишемического каскада», в контексте современного понимания приоритетной роли коррекции митохондриальной дисфункции в ограничении механизмов повреждения при церебральной ишемии. Обсуждаются возможности применения препаратов плейотропного нейропротекторного действия, реализующих митохондриально-направленные защитные эффекты через модуляцию активности транскрипционного коактиватора PGC-1α (peroxisome proliferator-activated receptor-1γ coactivator-1α), контролирующего процессы биогенеза митохондрий, ангиогенеза, ферментативное звено антиоксидантной системы. The review addresses modern approaches to pharmacological modulation of structure and function of the neuronal mitochondrial apparatus. This is a promising strategy for therapy of ischemic stroke, which accounts for up to 85% of all cases of acute cerebrovascular disease. The review analyzes classical concepts of neuroprotection as a therapy aimed at blocking key pathogenetic components of the “ischemic cascade”. These concepts are based on current ideas about the importance of correcting mitochondrial dysfunction for alleviation of damage in cerebral ischemia. The authors discussed possibilities of using pleiotropic neuroprotectors that implement mitochondrial-targeted protective effects by modulating the activity of transcriptional coactivator, peroxisome proliferator-activated receptor-1γ coactivator-1α (PGC-1α), which controls mitochondrial biogenesis, angiogenesis, and the enzymatic antioxidant system.

According to the World Health Organization, about 5 million people die every year from cerebrovascular disease. At the same time, the proportion of cerebral infarction, or ischemic stroke (IS), among forms of acute cerebrovascular accident reaches 80-85%. Despite the active study of biochemical and morphological changes leading to acute cerebrovascular ischemia, the problem of early diagnosis, prevention, as well as predicting the outcome of this disease is still relevant. There is no doubt that the interruption of the ischemic cascade at earlier stages can be accompanied by a greater effect of treatment. A timely and effective pharmacological intervention requires a clear understanding of the pathochemical and biological processes underlying acute ischemia at the molecular level. High mortality and disability accompanying acute IS, dictate the need to create new diagnostic and prognosis algorithms both in the acute period of IS, and in the recovery period. According to some authors, elucidation of the pathways that underlie the pathogenetic mechanisms acting in the penumbra are of great clinical interest for the development of new diagnostic and therapeutic strategies. Studying the mechanisms of apoptosis and autophagy of neurons in the dynamics of the acute period of IS, modulation of the autophagy process in the penumbra zone can contribute to the development of new methods for the diagnosis and treatment of acute IS. The review presents the results of the latest experimental studies on the role of apoptosis and autophagy in the development of acute cerebral ischemia and attempts to modulate these processes in order to influence the ischemic cascade. The review was based on sources from such international and national data bases as Scopus, Web of Science, Springer, RINC.

Stroke is a neurological emergency, where the mechanism of the blood supply to the brain is impaired, resulting in brain cell ischemia and death. Neuroinflammation is a key component in the ischemic cascade that results in cell damage and death after cerebral ischemia. The triggering receptor expressed on myeloid cells-1 (TREM-1) modulates neuroinflammation after acute ischemic stroke. In the present study, 60 patients with acute ischemic stroke, who had been subjected to neurological examinations and National Institutes of Health Stroke Scale (NIHSS) and brain magnetic resonance imaging studies, were enrolled in the emergency room of Kaohsiung Chang Gung Memorial Hospital. Twenty-four healthy volunteers were recruited as controls. The serum levels of soluble TREM-1 (sTREM-1), human S100 calcium-binding protein B (S100B), and proinflammatory cytokines and chemokines, including tumor necrosis &alpha, (TNF-&alpha, ), interleukin 1&beta, interleukin 6 (IL-6), interleukin 8, and interferon-&gamma, were measured immediately after acute ischemic stroke. The serum levels of sTREM-1, TNF&alpha, IL-6, and S100B were correlated with the stroke volume and NIHSS, after acute ischemic stroke. Additionally, the serum levels of sTREM-1 were significantly positively correlated with S100B. The functional outcomes were evaluated 6 months after ischemic stroke by the Barthel index, which was correlated with the age and levels of sTREM-1 and S100B. We suggest that acute ischemic stroke induces neuroinflammation by the activation of the TREM-1 signaling pathway and the downstream inflammatory machinery that modulates the inflammatory response and ischemic neuronal cell death. From a translational perspective, our results may allow for the development of a new therapeutic strategy for acute ischemic stroke by targeting the TREM-1 signaling pathway.

Ischemic stroke, characterized by the sudden loss of blood flow in specific area(s) of the brain, is the leading cause of permanent disability and is among the leading causes of death worldwide. The only approved pharmacological treatment for acute ischemic stroke (intravenous thrombolysis with recombinant tissue plasminogen activator) has significant clinical limitations and does not consider the complex set of events taking place after the onset of ischemic stroke (ischemic cascade), which is characterized by significant pro-oxidative events. The transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of a great number of antioxidant and/or defense proteins, has been pointed as a potential pharmacological target involved in the mitigation of deleterious oxidative events taking place at the ischemic cascade. This review summarizes studies concerning the protective role of Nrf2 in experimental models of ischemic stroke, emphasizing molecular events resulting from ischemic stroke that are, in parallel, modulated by Nrf2. Considering the acute nature of ischemic stroke, we discuss the challenges in using a putative pharmacological strategy (Nrf2 activator) that relies upon transcription, translation and metabolically active cells in treating ischemic stroke patients.

Objective To evaluate the distribution of capillary non-perfusion (CNP) in superficial and deep capillary plexuses (SCP and DCP) in eyes with diabetic retinopathy (DR). Methods In this retrospective case series, macular optical coherence tomography angiography (OCTA) images were obtained from eyes with DR without diabetic macular edema (DME). The area of CNP in SCP and DCP was delineated using an automated approach after excluding the foveal avascular zone (FAZ) and major retinal vessels. The distribution and spatial correlation of the CNP in each layer were analyzed. Results Forty-three eyes of 27 patients with DR with a mean age of 59.10 ± 9.05 years were included. The mean CNP area in SCP was statistically significantly higher than DCP (0.722 ± 0.437 mm2 vs. 0.184 ± 0.145 mm2 , respectively, p Conclusion In DR, SCP is more ischemic than DCP. This is in contrast to the previously described oxygenation-dependent ischemic cascade following acute retinal vascular occlusions. This study provides further insight into the retinal ischemia in DR.

Statistics of the World Health Organization (WHO) show that the cerebrovascular disease is the second most frequent cause of death and the third – as the main disabling factor in the working age population. Timely treatment is the key to quickly recovering ischemic tissue. According to the different ischemic cascade stages, the variety of the treatment combinations are proposed. American Stroke Association guidelines 2018 contains no neuroprotectors. In this regard, there remains a need for a biochemical agent successfully blocking one or more stages of the ischemic cascade, preventing cell apoptosis. Melatonin is also considered as such substance due to its neuroprotective properties. The main function of melatonin is the regulation of the sleep-wake cycle. The nuclear and membrane receptors in various organs determines other biological effects of this hormone. The ability of melatonin to regulate the blood pressure, oncogenesis, ovaries cycle, retina function and differentiation of osteoblasts was found. The significant neuroprotective potential of melatonin is realized through the antioxidant, anti-excitotoxic and anti-inflammatory properties. The positive effect on the ischemic lesion size and stroke-related pathological conditions (delirium, insomnia) has been demonstrated both in animal experiments and in clinical studies.

The ischemic cascade is initiated in the hypoperfused region of the brain that leads to neuronal cell death. Identification of multi-target inhibitor against prominent molecular mediators of ischemic cascade might be a suitable strategy to combat cerebral ischemic stroke. The present study is designed to evaluate the neuroprotective efficacy of chlorogenic acid (CGA) in the global cerebral ischemic rat model. The effective dose of CGA was evaluated on the basis of reduction in cerebral infarction area percentage, Evans blue extravasation, and restoration of brain water content. The expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and caspase-3 was evaluated by immunohistochemistry and morphological and cellular alterations in the cortex were observed by brain histology. The level of glutamate, calcium, and nitrate in different regions of the brain, as well as cerebrospinal fluid (CSF), was evaluated. The level of calcium and nitrate was compared with ifenprodil-an antagonist of N-methyl-D-aspartate receptor (NMDAR) and 7-nitroindazole-an inhibitor of neuronal nitric oxide synthase (nNOS) respectively. Further, molecular docking was performed to compare the inhibition potential of CGA against NMDAR and nNOS with their inhibitors. Dose optimization results revealed that intranasal administration of CGA (10 mg/kg b.w.) significantly reduced the cerebral infarction area, Evans blue extravasation and restored the brain water content compared with ischemia group. It also significantly reduced the calcium, nitrate, and glutamate levels compared with ischemia group in the cortex, hippocampus cerebellum, and CSF. Immunohistochemical analysis revealed that CGA significantly reduced the expression of TNF-α, iNOS, and caspase-3 as compared with the ischemia group. In molecular docking study, CGA displayed similar binding interaction as that of Ifenprodil and 7-nitroindazole with NMDAR and nNOS respectively. The current findings suggest that the treatment with CGA confers neuroprotection in global ischemic insult by inhibiting and downregulating the different molecular markers of cerebral ischemia.

The advent of mechanical thrombectomy and increasing alteplase use have transformed the care of patients with acute ischemic stroke. Patients with major arterial occlusions with poor outcomes now have a chance of returning to independent living in more than half of the cases. However, many patients with these severe strokes suffer major disability despite these therapies. The search is ongoing for agents that can be combined with thrombectomy to achieve better recovery through halting infarct growth and mitigating injury after ischemic stroke. Several studies in animals and humans have demonstrated that therapeutic hypothermia (TH) offers potential to interrupt the ischemic cascade, reduce infarct volume, and improve functional independence. We performed a literature search to look up recent advances in the use of TH surrounding the science, efficacy, and feasibility of inducing TH in modern stroke treatments. While protocols remain controversial, there is a real opportunity to combine TH with the existing therapies to improve outcome in adults with acute ischemic stroke.

Purpose To demonstrate the ability of widefield en face swept source optical coherence tomography (OCT) imaging to monitor peri-venular fern-like patterns of paracentral acute middle maculopathy (PAMM) associated with retinal arterial occlusions. Observations The peri-venular fern-like pattern of PAMM was diagnosed on the 12 × 12 mm en face structural OCT images from three patients. Fluorescein angiography images were unremarkable. Over time, all three patients demonstrated significant improvement in visual acuity with resolution of their peri-venular PAMM. Conclusions The peri-venular fern-like pattern of PAMM is usually associated with retinal vein occlusions, but we identified three cases with this pattern in eyes with presumed incomplete retinal arterial occlusions. Our cases support the ischemic cascade theory that begins within the deep capillary plexus and ascends in the retina depending on the severity of the ischemic event. Using the 12 × 12 mm en face structural OCT images, we are able to demonstrate a wider area of ischemia in PAMM compared with the traditional 6 × 6 mm scans.

Ischemic Stroke precedes depression . Post Stroke Depression (PSD) is a major driver for poor recovery, negative quality of life, poor rehabilitation outcomes and poor functional ability. This systematic reviews confirmed the post stroke depression as the norm as complex ischemic cascade involve the bioenergetic failure, deranged iron homeostasis ( calcium influx, Na influx, potassium efflux etc) excitotoxicity, acidotoxicity,disruption of the blood brain barrier, cytokine mediated cytotoxicity, reactive oxygen mediated toxicity , activation of cyclooxygenase pathway and generation of toxic products, infiltration of immune mediated cells resulting the cell death and deranged neuronal networks in mood related brain regions. This review focus on the pathobiology of stroke in the context and make the argument that PSD is the norm after a stroke rather than the exception.

Objectives: Baseline-core-infarct volume is a critical factor in patient selection and outcome in acute ischemic stroke (AIS) before mechanical thrombectomy (MT). We determined whether oxygen extraction efficiency and arterial collaterals, two different physiologic components of the cerebral ischemic cascade, interacted to modulate baseline-core-infarct volume in patients with AIS-LVO undergoing MT triage.Methods: Between January 2015 and March 2018, consecutive patients with an AIS and M1 occlusion considered for MT with a baseline MRI and perfusion-imaging were included. Variables such as baseline-core-infarct volume [mL], arterial collaterals (HIR: TMax > 10 s volume/TMax > 6 s), high oxygen extraction (HOE, presence of the brush-sign on T2*) were assessed. A linear-regression was used to test the interaction of HOE and HIR with baseline-core-infarct volume, after including potential confounding variables.Results: We included 103 patients. Median age was 70 (58–78), and 63% were female. Median baseline-core-infarct volume was 32 ml (IQR 8–74.5). Seventy six patients (74%) had HOE. In a multivariate analysis both favorable HIR collaterals (p = 0.02) and HOE (p = 0.038) were associated with lower baseline-core-infarct volume. However, HOE significantly interacted with HIR (p = 0.01) to predict baseline-core-infarct volume, favorable collaterals (low HIR) with HOE was associated with small baseline-core-infarct whereas patients with poor collaterals (high HIR) and HOE had large baseline-core-infarct.Conclusion: While HOE under effective collateral blood-flow has the lowest baseline-core-infarct volume of all patients, the protective effect of HOE reverses under poor collateral blood-flow and may be a maladaptive response to ischemic stroke as measured by core infarctions in AIS-LVO patients undergoing MT triage.

Инсульт ‒ вторая, а в некоторых странах ‒ третья причина смертности населения и одна из причин инвалидизации взрослого населения. Согласно статистике, в 2018 г. диагностировано 15 млн случаев инсульта и 6 млн летальных исходов. Единственными одобренными в настоящее время методами лечения острого инсульта являются внутривенное введение рекомбинантного тканевого активатора плазминогена (rtPA) и внутриартериальная тромбэктомия, которые используют менее чем у 10 и 1% пациентов соответственно.Обзор литературы посвящен патофизиологии и молекулярным механизмам повреждения при ишемии головного мозга. Обсуждается современная концепция двух стратегий клеточной терапии ‒ нейропротекции и ремоделирования, а также значение стволовых клеток в уменьшении местного и системного воспаления, нейрогенезе и ангиогенезе, повышении нейронной пластичности и защите гематоэнцефалического барьера. Показана роль паракринных факторов и внеклеточных везикул.Описаны методы доставки стволовых клеток (прямая интрацеребральная трансплантация, внутрижелудочковая и эндолюмбальная, внутривенная и внутриартериальная), количество клеток, их тип и оптимальное время доставки в зависимости от периода инсульта (острого, подострого и хронического). Представлены четыре вида канюль для трансплантации и их спецификация. Приведены данные о 15 завершенных клинических исследованиях с 2015 г. по настоящее время, в которых приняли участие 513 пациентов. Проведен подробный анализ эффективности и безопасности клеточной терапии., Інсульт ‒ друга, а в деяких країнах ‒ третя причина смертності населення та одна з причин інвалідизації дорослого населення. Згідно зі статистикою, в 2018 р. діагностовано 15 млн випадків інсульту і 6 млн летальніх наслідків. Єдиними схваленими нині методами лікування гострого інсульту є внутрішньовенне введення рекомбінантного тканинного активатора плазміногену (rtPA) і внутрішньоартеріальна тромбектомія, які використовують менше ніж у 10 та 1% пацієнтів відповідно.Огляд літератури присвячений патофізіології та молекулярним механізмам ушкодження при ішемії головного мозку. Обговорюється сучасна концепція двох стратегій клітинної терапії ‒ нейропротекції та ремоделювання, а також значення стовбурових клітин у зменшенні місцевого і системного запалення, нейрогенезi та ангіогенезi, підвищенні нейронної пластичності, захисті гематоенцефалічного бар’єра. Показана роль паракрінних факторів і позаклітинних везикул.Описано методи доставки стовбурових клітин (пряма інтрацеребральна трансплантація, внутрішньошлуночкова і ендолюмбальна, внутрішньовенна та внутрішньоартеріальна), кількість клітин, їх тип і оптимальний час доставки залежно від періоду інсульту (гострого, підгострого і хронічного). Представлено чотири види канюль для трансплантації та їх специфікацію. Наведено дані щодо 15 завершених клінічних досліджень з 2015 р. дотепер, в яких взяли участь 513 пацієнтів. Проведено детальний аналіз ефективності та безпечності клітинної терапії., Stroke is the second, and in some countries the third cause of mortality in the population and one of the causes of disability in the adult population. According to statistics, in 2018, 15 million cases of stroke and 6 million deaths were diagnosed,The only currently approved treatments for acute stroke are intravenous tissue plasminogen activator (rtPA) and intra-arterial thrombectomy, which are used in less than 10% and 1% of patients, respectively.The literature review is devoted to the pathophysiology and molecular mechanisms of damage in cerebral ischemia. The modern concept of two strategies of cell therapy is discussed: neuroprotection and remodeling; the role of stem cells in reducing local and systemic inflammation, neurogenesis and angiogenesis, increasing neuronal plasticity, and protecting the blood-brain barrier, the role of paracrine factors and extracellular vesicles is shown.Methods of stem cell delivery are described: direct intracerebral transplantation, intraventricular and intrathecal, intravenous and intraarterial; the number of cells, their type and optimal delivery time depending on the acute, subacute and chronic periods of stroke. We also described recently designed the radially branched deployment (RBD) device and Cleveland multiport catheter for convection-enhanced delivery in which a cell-delivery catheter can be deployed at various angles and depths from a single longitudinal cannula. Finally, data on the completed 15 clinical trials from 2015 to the present, in which 513 patients took part, are presented. A detailed analysis of the efficacy and safety of cell therapy has been carried out.

Purpose To report a case of paracentral acute middle maculopathy (PAMM) and evidence of the ischemic cascade documented with spectral domain optical coherence tomography (SD-OCT) following radiation treatment of a choroidal melanoma. Observations A healthy young patient was evaluated for an asymptomatic choroidal nevus in the left eye. Fundus examination was remarkable for a choroidal melanocytic lesion that measured 1.8 mm in thickness by initial B-scan ultrasound. Clinical examination 6 months later showed growth of the tumor at several margins with new subretinal fluid, and a B-scan measured thickness of 1.9 mm. The lesion was diagnosed as a small choroidal melanoma and treated with gamma knife radiation with a dose of 3000 cGy. Sixteen months later, examination showed signs of radiation retinopathy including cotton wool spots and PAMM via SD-OCT and OCT angiography and evidence of the ischemic cascade i.e. alternating zones of middle and combined middle and inner retinal layer infarction. Conclusions and Importance: Radiation retinopathy can include signs of microvascular damage and ischemia including lesions such as cotton wool spots and PAMM. A case is presented in this report of radiation retinopathy with OCT evidence of PAMM and the ischemic cascade.

Cerebral ischemia constitutes the most frequent type of cerebrovascular disease. The reduction of blood supply to the brain initiates the ischemic cascade starting from ionic imbalance to subsequent glutamate excitotoxicity, neuroinflammation and oxidative stress, eventually causing neuronal death. Previously, the authors have demonstrated the in vitro cytoprotective and antioxidant effects of a new arylidene malonate derivative, KM-34, against oxidizing agents like hydrogen peroxide, glutamate or Fe3+/ascorbate. Here, we examined for the first time the neuroprotective effect of KM-34 on ischemia/reperfusion models. In vitro, treatment with 10 and 50 μM KM-34 reduced the cellular death (propidium iodide incorporation) induced by oxygen glucose deprivation (OGD) in rat organotypic hippocampal slices cultures. In vivo, stroke was induced in male Wistar rats through middle cerebral artery occlusion (MCAO), followed by 23 h of reperfusion. KM-34 was orally administered 105 min after MCAO onset. We noticed that 1 mg/kg KM-34 reduced infarct volume and neurological score, and increased the latency to fall in the Hanging Wire test compared to vehicle-treated ischemic animals. While ischemic and sham-operated groups showed similar horizontal locomotor activity, vertical counts decreased after MCAO, suggesting that vertical movements are more sensitive to the ischemic injury. Treatment with KM-34 also alleviated the mitochondrial impairment (ROS generation, swelling and membrane potential dissipation) induced by transient MCAO but not significant alterations were found in oxidative stress parameters. Overall, the study provides preclinical evidences confirming the neuroprotective effects of a novel synthetic molecule and paved the way for future investigations regarding its therapeutic potential against brain ischemia/reperfusion injury.

To report a case of branch retinal artery occlusion associated with paracentral acute middle maculopathy on spectral-domain optical coherence tomography presumably related to heavy cannabis consumption.Retrospective case report. Spectral-domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed.A 21-year-old healthy man described the acute onset of superior visual field loss in his right eye. He admitted smoking approximately 15 g daily of cannabis for several weeks during COVID-19 confinement. Ophthalmoscopic examination of the right eye showed inferotemporal retinal whitening. Spectral-domain optical coherence tomography illustrated evidence of the ischemic cascade with diffuse hyperreflectivity of the inner and middle retinal layers within the central region of the retinal infarct and paracentral acute middle maculopathy at the border of the infarct. Optical coherence tomography angiography demonstrated predominant flow signal loss at the level of the deep retinal capillary plexus. Fluorescein angiography and complete systemic workup were unremarkable.Branch retinal artery occlusion and paracentral acute middle maculopathy may be related to heavy cannabis use as the result of transient arterial vasospasm.