Eastern Equine Encephalitis Virus: A Case Report and Brief Literature Review of Current Therapeutic and Preventative Strategies.

Background: Eastern equine encephalitis virus (EEEV) is a rare mosquito-borne illness exhibiting rapid neurological deterioration and permanent damage. Despite its >30% mortality and >60% long-term neurological damage, EEEV has no approved antiviral medication or vaccination. This report uniquely aims to describe a rare case of EEEV and provide a current literature review of therapeutic and preventative options from the clinical perspective to guide clinicians and public health workers, along with informing them about its impact and current knowledge gaps. Methods: A retrospective chart review of the electronic medical record was performed for a patient's 10-day hospital admission in July 2021. In addition, PubMed was searched using relevant keywords for a literature review of EEEV. Results: A 61-year-old woman presented with dysarthria and right-sided facial droop. Acute ischemic stroke was ruled out, and empiric intravenous (IV) antibiotics were initiated for possible infectious etiology. The patient developed worsening mental status and fever and was intubated, with antibiotics broadened with concern for meningitis along with tick-borne illness. The patient remained encephalopathic and febrile, and lumbar serologies were consistent with viral meningoencephalitis or acute disseminated encephalomyelitis. Several days after collection, quantitative antibody testing returned positive for EEEV. The patient was pronounced dead on hospital day 10. On review of the literature regarding EEEV, supportive care and prevention remain the cornerstone of management. Although early IV immunoglobulin and high-dose steroids have shown potential as treatments to reduce morbidity and mortality, no vaccines have been approved to date. Conclusion: Prospective trials and further investigations into treatment and preventative options may be useful in reducing the morbidity and mortality associated with EEEV.

Suspected spontaneous early hemorrhagic transformation of multiple ischemic strokes secondary to primary splenic torsion in a German Shepherd dog.

A 3-year-old female German Shepherd dog was presented with generalized tonic-clonic epileptic seizures, right-sided central vestibular syndrome, and right trigeminal nerve dysfunction. Acute lacunar ischemic strokes within both thalami, right side of the mesencephalon, left side of the myelencephalon, both sides of the cervical spinal cord, and acute hemorrhagic strokes within the rostral part of the right cerebellar hemisphere and right rostral colliculus were identified on magnetic resonance imaging. Additional evaluation identified multiple renal infarcts and complete splenic torsion, with entrapment of the left pancreatic lobe. Medical management, splenectomy, partial pancreatectomy, and intensive physical rehabilitation led to clinical improvement. The histology of the spleen was consistent with hemorrhagic infarction. Three months after onset, neurological examination identified only mild vestibular sequelae. The final diagnosis was multiple ischemic strokes secondary to primary splenic torsion. Spontaneous early hemorrhagic transformation, a well-known condition in human medicine, also was found in this case.

Identification of changed proteins by retinoic acid in cerebral ischemic damage: a proteomic study.

Ischemic stroke is a severe neurodegenerative disease with a high mortality rate. Retinoic acid is a representative metabolite of vitamin A. It has many beneficial effects including anti-inflammatory, anti-apoptotic, and neuroprotective effects. The purpose of this study is to identify specific proteins that are regulated by retinoic acid in ischemic stroke. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected intraperitoneally into male rats for four days prior to MCAO operation. Neurobehavioral tests were performed 24 hr after MCAO and the cerebral cortex was collected for proteomic study. Retinoic acid alleviates neurobehavioral deficits and histopathological changes caused by MCAO. Furthermore, we identified various proteins that were altered by retinoic acid in MCAO damage. Among these identified proteins, adenosylhomocysteinase, isocitrate dehydrogenase [NAD+] subunit α, glycerol-3-phosphate dehydrogenase, Rab GDP dissociation inhibitor ß, and apolipoprotein A1 were down-regulated in MCAO animals with vehicle treatment, whereas retinoic acid treatment alleviated these reductions. However, heat shock protein 60 was up-regulated in MCAO animals with vehicle, while retinoic acid treatment attenuated this increase. The changes in these expressions were confirmed by reverse transcription-PCR. These proteins regulate cell metabolism and mediate stress responses. Our results demonstrated that retinoic acid attenuates the neuronal damage by MCAO and regulates the various protein expressions that are involved in the survival of cells. Thus, we can suggest that retinoic acid exerts neuroprotective effects on focal cerebral ischemia by modulation of specific proteins.

Quantitative Proteomic Analysis of Plasma after Remote Ischemic Conditioning in a Rhesus Monkey Ischemic Stroke Model.

BACKGROUND: Animal and clinical studies have shown that remote ischemic conditioning (RIC) has protective effects for cerebral vascular diseases, with induced humoral factor changes in the peripheral blood. However, many findings are heterogeneous, perhaps due to differences in the RIC intervention schemes, enrolled populations, and sample times. This study aimed to examine the RIC-induced changes in the plasma proteome using rhesus monkey models of strokes. METHODS: Two adult rhesus monkeys with autologous blood clot-induced middle cerebral artery (MCA) occlusion underwent RIC interventions twice a week for five consecutive weeks. Each RIC treatment included five cycles of five minutes of ischemia alternating with five minutes of reperfusion of the forearm. The blood samples were taken from the median cubital vein of the monkeys at baseline and immediately after each week's RIC stimulus. The plasma samples were isolated for a proteomic analysis using mass spectrometry (MS). RESULTS: Several proteins related to lipid metabolism (Apolipoprotein A-II and Apolipoprotein C-II), coagulation (Fibrinogen alpha chain and serpin), immunoinflammatory responses (complement C3 and C1), and endovascular hemostasis (basement membrane-specific heparan sulfate proteoglycan) were significantly modulated after the RIC intervention. Many of these induced changes, such as in the lipid metabolism regulation and anticoagulation responses, starting as early as two weeks following the RIC intervention. The complementary activation and protection of the endovascular cells occurred more than three weeks postintervention. CONCLUSIONS: Multiple protective effects were induced by RIC and involved lipid metabolism regulation (anti-atherogenesis), anticoagulation (antithrombosis), complement activation, and endovascular homeostasis (anti-inflammation). In conclusion, this study indicates that RIC results in significant modulations of the plasma proteome. It also provides ideas for future research and screening targets.

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

Primary hyperlipidemia with associated ischemic strokes in a West Highland white terrier dog.

A 3-year-old spayed female, West Highland white terrier dog was evaluated because of a 4-month history of recurrent brain clinical signs. Magnetic resonance imaging (MRI) revealed multifocal brain lesions consistent with ischemic injuries. Blood analysis was unremarkable aside from severe hypertriglyceridemia and hypercholesterolemia with no underlying cause, suggesting primary hyperlipidemia. The patient was treated for hyperlipidemia and started on a low-fat diet and omega-3 supplementation. Clinical signs resolved over the following 12 months along with improvement in lipidemia. This represents the first reported case of MRI findings suggestive of multiple cerebrovascular injuries associated with primary hyperlipidemia in a dog, and the first primary hyperlipidemia reported in a West Highland white terrier dog.

Hyperlipidémie primaire associée à des accidents vasculaires cérébraux ischémiques chez un chien terrier West Highland white. Une femelle stérilisée West Highland white âgée de 3 ans fut évaluée à cause d'une histoire de signes cliniques cérébraux récurrents d'une durée de 4 mois. Une imagerie par résonnance magnétique (RMI) révéla des lésions cérébrales multifocales compatibles avec des blessures ischémiques. Une analyse sanguine s'avéra peu concluante sauf pour une hypertriglycéridémie et une hypercholestérolémie sévère sans cause sous-jacente, suggérant une hyperlipidémie primaire. Le patient fut traité pour l'hyperlipidémie et débuta une diète faible en gras et une supplémentation en oméga-3. Les signes cliniques se sont résolus dans les 12 mois suivants avec une amélioration de la lipidémie. Ceci représente le premier cas rapporté de trouvailles par MRI suggestives de lésions cérébro-vasculaires multiples associées avec une hyperlipidémie primaire chez un chien, et le premier cas d'hyperlipidémie primaire rapporté chez un terrier West Highland white.(Traduit par Dr Serge Messier).

Cerebral Computed Tomography Scan Demonstrating Ischemic Stroke in a Filly After Intravenous Antibiotic Administration.

Performing a brain computerized tomography scan (CT scan) on a foal requires specific equipment and anesthesia for large animals. However, the information obtained may demonstrate lesions responsible for the neurological deficits. Especially, CT scan findings may help to understand a mechanism of cerebral ischemia. Indeed, categories of cerebral ischemia are divided in three types: territorial infarctions (downstream of the territory of an artery), watershed infarctions (slow-flow at the junction of two arterial territories), and lacunar infarctions (small-vessel occlusions). Hypersensitivity reactions and type I anaphylactic IgE antibody reactions are severe potential adverse effects of sulfonamide administration, which occur in about three percent of cases. In horses, anaphylaxis is often clinically expressed as hypotension and collapse. Cardiovascular collapse may lead to multiorgan slow-flow leading to infarction with multiorgan failure and death. We report the case of a filly that suffered a presumed watershed cerebral infarction after antibiotic injection, indicated on a brain CT scan. This was attributed to a cerebral slow-flow during cardiovascular collapse, at the posterior junction of the right cerebral arteries. No abnormalities were initially identified on the CT scan; however, a review of the imaging by a radiologist specialized in cerebrovascular diseases detected a limited right occipital cortico-subcortical lesion in the visual cortex, interpreted as an ischemic scar in the watershed area related to hemodynamic infarction. This case highlights that detection of brain lesions by CT scan might require specialized knowledge and careful reading for interpretation particularly in the case of limited lesions.