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• Clinical course of a 66-year-old man with an acute ischaemic stroke in the setting of a COVID-19 infection
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• http://orcid.org/0000-0002-7441-6952 Saajan Basi 1 , 2 ,
• Mohammad Hamdan 1 and
• Shuja Punekar 1
• 1 Department of Stroke and Acute Medicine , King's Mill Hospital , Sutton-in-Ashfield , UK
• 2 Department of Acute Medicine , University Hospitals of Derby and Burton , Derby , UK
• Correspondence to Dr Saajan Basi; saajan.basi{at}nhs.net

A 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. The cerebral infarct was confirmed with CT imaging. The only evidence of respiratory symptoms on admission was a 2 L oxygen requirement, maintaining oxygen saturations between 88% and 92%. In a matter of hours this patient developed a greater oxygen requirement, alongside reduced levels of consciousness. A positive COVID-19 throat swab, in addition to bilateral pneumonia on chest X-ray and lymphopaenia in his blood tests, confirmed a diagnosis of COVID-19 pneumonia. A proactive decision was made involving the patients’ family, ward and intensive care healthcare staff, to not escalate care above a ward-based ceiling of care. The patient died 5 days following admission under the palliative care provided by the medical team.

• respiratory medicine
• infectious diseases
• global health

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https://doi.org/10.1136/bcr-2020-235920

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SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a new strain of coronavirus that is thought to have originated in December 2019 in Wuhan, China. In a matter of months, it has erupted from non-existence to perhaps the greatest challenge to healthcare in modern times, grinding most societies globally to a sudden halt. Consequently, the study and research into SARS-CoV-2 is invaluable. Although coronaviruses are common, SARS-CoV-2 appears to be considerably more contagious. The WHO figures into the 2003 SARS-CoV-1 outbreak, from November 2002 to July 2003, indicate a total of 8439 confirmed cases globally. 1 In comparison, during a period of 4 months from December 2019 to July 2020, the number of global cases of COVID-19 reached 10 357 662, increasing exponentially, illustrating how much more contagious SARS-CoV-2 has been. 2

Previous literature has indicated infections, and influenza-like illness have been associated with an overall increase in the odds of stroke development. 3 There appears to be a growing correlation between COVID-19 positive patients presenting to hospital with ischaemic stroke; however, studies investigating this are in progress, with new data emerging daily. This patient report comments on and further characterises the link between COVID-19 pneumonia and the development of ischaemic stroke. At the time of this patients’ admission, there were 95 positive cases from 604 COVID-19 tests conducted in the local community, with a predicted population of 108 000. 4 Only 4 days later, when this patient died, the figure increased to 172 positive cases (81% increase), illustrating the rapid escalation towards the peak of the pandemic, and widespread transmission within the local community ( figure 1 ). As more cases of ischaemic stroke in COVID-19 pneumonia patients arise, the recognition and understanding of its presentation and aetiology can be deciphered. Considering the virulence of SARS-CoV-2 it is crucial as a global healthcare community, we develop this understanding, in order to intervene and reduce significant morbidity and mortality in stroke patients.

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A graph showing the number of patients with COVID-19 in the hospital and in the community over time.

Case presentation

A 66-year-old man presented to the hospital with signs of left-sided weakness. The patient had a background of chronic obstructive pulmonary disease (COPD), atrial fibrillation and had one previous ischaemic stroke, producing left-sided haemiparesis, which had completely resolved. He was a non-smoker and lived in a house. The patient was found slumped over on the sofa at home on 1 April 2020, by a relative at approximately 01:00, having been seen to have no acute medical illness at 22:00. The patients’ relative initially described disorientation and agitation with weakness noted in the left upper limb and dysarthria. At the time of presentation, neither the patient nor his relative identified any history of fever, cough, shortness of breath, loss of taste, smell or any other symptoms; however, the patient did have a prior admission 9 days earlier with shortness of breath.

The vague nature of symptoms, entwined with considerable concern over approaching the hospital, due to the risk of contracting COVID-19, created a delay in the patients’ attendance to the accident and emergency department. His primary survey conducted at 09:20 on 1 April 2020 demonstrated a patent airway, with spontaneous breathing and good perfusion. His Glasgow Coma Scale (GCS) score was 15 (a score of 15 is the highest level of consciousness), his blood glucose was 7.2, and he did not exhibit any signs of trauma. His abbreviated mental test score was 7 out of 10, indicating a degree of altered cognition. An ECG demonstrated atrial fibrillation with a normal heart rate. His admission weight measured 107 kg. At 09:57 the patient required 2 L of nasal cannula oxygen to maintain his oxygen saturations between 88% and 92%. He started to develop agitation associated with an increased respiratory rate at 36 breaths per minute. On auscultation of his chest, he demonstrated widespread coarse crepitation and bilateral wheeze. Throughout he was haemodynamically stable, with a systolic blood pressure between 143 mm Hg and 144 mm Hg and heart rate between 86 beats/min and 95 beats/min. From a neurological standpoint, he had a mild left facial droop, 2/5 power in both lower limbs, 2/5 power in his left upper limb and 5/5 power in his right upper limb. Tone in his left upper limb had increased. This patient was suspected of having COVID-19 pneumonia alongside an ischaemic stroke.

Investigations

A CT of his brain conducted at 11:38 on 1 April 2020 ( figure 2 ) illustrated an ill-defined hypodensity in the right frontal lobe medially, with sulcal effacement and loss of grey-white matter. This was highly likely to represent acute anterior cerebral artery territory infarction. Furthermore an oval low-density area in the right cerebellar hemisphere, that was also suspicious of an acute infarction. These vascular territories did not entirely correlate with his clinical picture, as limb weakness is not as prominent in anterior cerebral artery territory ischaemia. Therefore this left-sided weakness may have been an amalgamation of residual weakness from his previous stroke, in addition to his acute cerebral infarction. An erect AP chest X-ray with portable equipment ( figure 3 ) conducted on the same day demonstrated patchy peripheral consolidation bilaterally, with no evidence of significant pleural effusion. The pattern of lung involvement raised suspicion of COVID-19 infection, which at this stage was thought to have provoked the acute cerebral infarct. Clinically significant blood results from 1 April 2020 demonstrated a raised C-reactive protein (CRP) at 215 mg/L (normal 0–5 mg/L) and lymphopaenia at 0.5×10 9 (normal 1×10 9 to 3×10 9 ). Other routine blood results are provided in table 1 .

CT imaging of this patients’ brain demonstrating a wedge-shaped infarction of the anterior cerebral artery territory.

Chest X-ray demonstrating the bilateral COVID-19 pneumonia of this patient on admission.

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Clinical biochemistry and haematology blood results of the patient

Interestingly the patient, in this case, was clinically assessed in the accident and emergency department on 23 March 2020, 9 days prior to admission, with symptoms of shortness of breath. His blood results from this day showed a CRP of 22 mg/L and a greater lymphopaenia at 0.3×10 9 . He had a chest X-ray ( figure 4 ), which indicated mild radiopacification in the left mid zone. He was initially treated with intravenous co-amoxiclav and ciprofloxacin. The following day he had minimal symptoms (CURB 65 score 1 for being over 65 years). Given improving blood results (declining CRP), he was discharged home with a course of oral amoxicillin and clarithromycin. As national governmental restrictions due to COVID-19 had not been formally announced until 23 March 2020, and inconsistencies regarding personal protective equipment training and usage existed during the earlier stages of this rapidly evolving pandemic, it is possible that this patient contracted COVID-19 within the local community, or during his prior hospital admission. It could be argued that the patient had early COVID-19 signs and symptoms, having presented with shortness of breath, lymphopaenia, and having had subtle infective chest X-ray changes. The patient explained he developed a stagnant productive cough, which began 5 days prior to his attendance to hospital on 23 March 2020. He responded to antibiotics, making a full recovery following 7 days of treatment. This information does not assimilate with the typical features of a COVID-19 infection. A diagnosis of community-acquired pneumonia or infective exacerbation of COPD seem more likely. However, given the high incidence of COVID-19 infections during this patients’ illness, an exposure and early COVID-19 illness, prior to the 23 March 2020, cannot be completely ruled out.

Chest X-ray conducted on prior admission illustrating mild radiopacification in the left mid zone.

On the current admission, this patient was managed with nasal cannula oxygen at 2 L. By the end of the day, this had progressed to a venturi mask, requiring 8 L of oxygen to maintain oxygen saturation. He had also become increasingly drowsy and confused, his GCS declined from 15 to 12. However, the patient was still haemodynamically stable, as he had been in the morning. An arterial blood gas demonstrated a respiratory alkalosis (pH 7.55, pCO 2 3.1, pO 2 6.7 and HCO 3 24.9, lactate 1.8, base excess 0.5). He was commenced on intravenous co-amoxiclav and ciprofloxacin, to treat a potential exacerbation of COPD. This patient had a COVID-19 throat swab on 1 April 2020. Before the result of this swab, an early discussion was held with the intensive care unit staff, who decided at 17:00 on 1 April 2020 that given the patients presentation, rapid deterioration, comorbidities and likely COVID-19 diagnosis he would not be for escalation to the intensive care unit, and if he were to deteriorate further the end of life pathway would be most appropriate. The discussion was reiterated to the patients’ family, who were in agreement with this. Although he had evidence of an ischaemic stroke on CT of his brain, it was agreed by all clinicians that intervention for this was not as much of a priority as providing optimal palliative care, therefore, a minimally invasive method of treatment was advocated by the stroke team. The patient was given 300 mg of aspirin and was not a candidate for fibrinolysis.

Outcome and follow-up

The following day, before the throat swab result, had appeared the patient deteriorated further, requiring 15 L of oxygen through a non-rebreather face mask at 60% FiO 2 to maintain his oxygen saturation, at a maximum of 88% overnight. At this point, he was unresponsive to voice, with a GCS of 5. Although, he was still haemodynamically stable, with a blood pressure of 126/74 mm Hg and a heart rate of 98 beats/min. His respiratory rate was 30 breaths/min. His worsening respiratory condition, combined with his declining level of consciousness made it impossible to clinically assess progression of the neurological deficit generated by his cerebral infarction. Moreover, the patient was declining sharply while receiving the maximal ward-based treatment available. The senior respiratory physician overseeing the patients’ care decided that a palliative approach was in this his best interest, which was agreed on by all parties. The respiratory team completed the ‘recognising dying’ documentation, which signified that priorities of care had shifted from curative treatment to palliative care. Although the palliative team was not formally involved in the care of the patient, the patient received comfort measures without further attempts at supporting oxygenation, or conduction of regular clinical observations. The COVID-19 throat swab confirmed a positive result on 2 April 2020. The patient was treated by the medical team under jurisdiction of the hospital palliative care team. This included the prescribing of anticipatory medications and a syringe driver, which was established on 3 April 2020. His antibiotic treatment, non-essential medication and intravenous fluid treatment were discontinued. His comatose condition persisted throughout the admission. Once the patients’ GCS was 5, it did not improve. The patient was pronounced dead by doctors at 08:40 on 5 April 2020.

SARS-CoV-2 is a type of coronavirus that was first reported to have caused pneumonia-like infection in humans on 3 December 2019. 5 As a group, coronaviruses are a common cause of upper and lower respiratory tract infections (especially in children) and have been researched extensively since they were first characterised in the 1960s. 6 To date, there are seven coronaviruses that are known to cause infection in humans, including SARS-CoV-1, the first known zoonotic coronavirus outbreak in November 2002. 7 Coronavirus infections pass through communities during the winter months, causing small outbreaks in local communities, that do not cause significant mortality or morbidity.

SARS-CoV-2 strain of coronavirus is classed as a zoonotic coronavirus, meaning the virus pathogen is transmitted from non-humans to cause disease in humans. However the rapid spread of SARS-CoV-2 indicates human to human transmission is present. From previous research on the transmission of coronaviruses and that of SARS-CoV-2 it can be inferred that SARS-CoV-2 spreads via respiratory droplets, either from direct inhalation, or indirectly touching surfaces with the virus and exposing the eyes, nose or mouth. 8 Common signs and symptoms of the COVID-19 infection identified in patients include high fevers, severe fatigue, dry cough, acute breathing difficulties, bilateral pneumonia on radiological imaging and lymphopaenia. 9 Most of these features were identified in this case study. The significance of COVID-19 is illustrated by the speed of its global spread and the potential to cause severe clinical presentations, which as of April 2020 can only be treated symptomatically. In Italy, as of mid-March 2020, it was reported that 12% of the entire COVID-19 positive population and 16% of all hospitalised patients had an admission to the intensive care unit. 10

The patient, in this case, illustrates the clinical relevance of understanding COVID-19, as he presented with an ischaemic stroke underlined by minimal respiratory symptoms, which progressed expeditiously, resulting in acute respiratory distress syndrome and subsequent death.

Our case is an example of a new and ever-evolving clinical correlation, between patients who present with a radiological confirmed ischaemic stroke and severe COVID-19 pneumonia. As of April 2020, no comprehensive data of the relationship between ischaemic stroke and COVID-19 has been published, however early retrospective case series from three hospitals in Wuhan, China have indicated that up to 36% of COVID-19 patients had neurological manifestations, including stroke. 11 These studies have not yet undergone peer review, but they tell us a great deal about the relationship between COVID-19 and ischaemic stroke, and have been used to influence the American Heart Associations ‘Temporary Emergency Guidance to US Stroke Centres During the COVID-19 Pandemic’. 12

The relationship between similar coronaviruses and other viruses, such as influenza in the development of ischaemic stroke has previously been researched and provide a basis for further investigation, into the prominence of COVID-19 and its relation to ischaemic stroke. 3 Studies of SARS-CoV-2 indicate its receptor-binding region for entry into the host cell is the same as ACE2, which is present on endothelial cells throughout the body. It may be the case that SARS-CoV-2 alters the conventional ability of ACE2 to protect endothelial function in blood vessels, promoting atherosclerotic plaque displacement by producing an inflammatory response, thus increasing the risk of ischaemic stroke development. 13

Other hypothesised reasons for stroke development in COVID-19 patients are the development of hypercoagulability, as a result of critical illness or new onset of arrhythmias, caused by severe infection. Some case studies in Wuhan described immense inflammatory responses to COVID-19, including elevated acute phase reactants, such as CRP and D-dimer. Raised D-dimers are a non-specific marker of a prothrombotic state and have been associated with greater morbidity and mortality relating to stroke and other neurological features. 14

Arrhythmias such as atrial fibrillation had been identified in 17% of 138 COVID-19 patients, in a study conducted in Wuhan, China. 15 In this report, the patient was known to have atrial fibrillation and was treated with rivaroxaban. The acute inflammatory state COVID-19 is known to produce had the potential to create a prothrombotic environment, culminating in an ischaemic stroke.

Some early case studies produced in Wuhan describe patients in the sixth decade of life that had not been previously noted to have antiphospholipid antibodies, contain the antibodies in blood results. They are antibodies signify antiphospholipid syndrome; a prothrombotic condition. 16 This raises the hypothesis concerning the ability of COVID-19 to evoke the creation of these antibodies and potentiate thrombotic events, such as ischaemic stroke.

No peer-reviewed studies on the effects of COVID-19 and mechanism of stroke are published as of April 2020; therefore, it is difficult to evidence a specific reason as to why COVID-19 patients are developing neurological signs. It is suspected that a mixture of the factors mentioned above influence the development of ischaemic stroke.

If we delve further into this patients’ comorbid state exclusive to COVID-19 infection, it can be argued that this patient was already at a relatively higher risk of stroke development compared with the general population. The fact this patient had previously had an ischaemic stroke illustrates a prior susceptibility. This patient had a known background of hypertension and atrial fibrillation, which as mentioned previously, can influence blood clot or plaque propagation in the development of an acute ischaemic event. 15 Although the patient was prescribed rivaroxaban as an anticoagulant, true consistent compliance to rivaroxaban or other medications such as amlodipine, clopidogrel, candesartan and atorvastatin cannot be confirmed; all of which can contribute to the reduction of influential factors in the development of ischaemic stroke. Furthermore, the fear of contracting COVID-19, in addition to his vague symptoms, unlike his prior ischaemic stroke, which demonstrated dense left-sided haemiparesis, led to a delay in presentation to hospital. This made treatment options like fibrinolysis unachievable, although it can be argued that if he was already infected with COVID-19, he would have still developed life-threatening COVID-19 pneumonia, regardless of whether he underwent fibrinolysis. It is therefore important to consider that if this patient did not contract COVID-19 pneumonia, he still had many risk factors that made him prone to ischaemic stroke formation. Thus, we must consider whether similar patients would suffer from ischaemic stroke, regardless of COVID-19 infection and whether COVID-19 impacts on the severity of the stroke as an entity.

Having said this, the management of these patients is dependent on the likelihood of a positive outcome from the COVID-19 infection. Establishing the ceiling of care is crucial, as it prevents incredibly unwell or unfit patients’ from going through futile treatments, ensuring respect and dignity in death, if this is the likely outcome. It also allows for the provision of limited or intensive resources, such as intensive care beds or endotracheal intubation during the COVID-19 pandemic, to those who are assessed by the multidisciplinary team to benefit the most from their use. The way to establish this ceiling of care is through an early multidisciplinary discussion. In this case, the patient did not convey his wishes regarding his care to the medical team or his family; therefore it was decided among intensive care specialists, respiratory physicians, stroke physicians and the patients’ relatives. The patient was discussed with the intensive care team, who decided that as the patient sustained two acute life-threatening illnesses simultaneously and had rapidly deteriorated, ward-based care with a view to palliate if the further deterioration was in the patients’ best interests. These decisions were not easy to make, especially as it was on the first day of presentation. This decision was made in the context of the patients’ comorbidities, including COPD, the patients’ age, and the availability of intensive care beds during the steep rise in intensive care admissions, in the midst of the COVID-19 pandemic ( figure 1 ). Furthermore, the patients’ rapid and permanent decline in GCS, entwined with the severe stroke on CT imaging of the brain made it more unlikely that significant and permanent recovery could be achieved from mechanical intubation, especially as the damage caused by the stroke could not be significantly reversed. As hospitals manage patients with COVID-19 in many parts of the world, there may be tension between the need to provide higher levels of care for an individual patient and the need to preserve finite resources to maximise the benefits for most patients. This patient presented during a steep rise in intensive care admissions, which may have influenced the early decision not to treat the patient in an intensive care setting. Retrospective studies from Wuhan investigating mortality in patients with multiple organ failure, in the setting of COVID-19, requiring intubation have demonstrated mortality can be up to 61.5%. 17 The mortality risk is even higher in those over 65 years of age with respiratory comorbidities, indicating why this patient was unlikely to survive an admission to the intensive care unit. 18

Regularly updating the patients’ family ensured cooperation, empathy and sympathy. The patients’ stroke was not seen as a priority given the severity of his COVID-19 pneumonia, therefore the least invasive, but most appropriate treatment was provided for his stroke. The British Association of Stroke Physicians advocate this approach and also request the notification to their organisation of COVID-19-related stroke cases, in the UK. 19

Learning points

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is one of seven known coronaviruses that commonly cause upper and lower respiratory tract infections. It is the cause of the 2019–2020 global coronavirus pandemic.

The significance of COVID-19 is illustrated by the rapid speed of its spread globally and the potential to cause severe clinical presentations, such as ischaemic stroke.

Early retrospective data has indicated that up to 36% of COVID-19 patients had neurological manifestations, including stroke.

Potential mechanisms behind stroke in COVID-19 patients include a plethora of hypercoagulability secondary to critical illness and systemic inflammation, the development of arrhythmia, alteration to the vascular endothelium resulting in atherosclerotic plaque displacement and dehydration.

It is vital that effective, open communication between the multidisciplinary team, patient and patients relatives is conducted early in order to firmly establish the most appropriate ceiling of care for the patient.

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• British Association of Stroke Physicians

Contributors SB was involved in the collecting of information for the case, the initial written draft of the case and researching existing data on acute stroke and COVID-19. He also edited drafts of the report. MH was involved in reviewing and editing drafts of the report and contributing new data. SP oversaw the conduction of the project and contributed addition research papers.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient consent for publication Next of kin consent obtained.

Provenance and peer review Not commissioned; externally peer reviewed.

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Chapter 7:  10 Real Cases on Transient Ischemic Attack and Stroke: Diagnosis, Management, and Follow-Up

Jeirym Miranda; Fareeha S. Alavi; Muhammad Saad

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Case review, case discussion, clinical symptoms.

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Case 1: Management of Acute Thrombotic Cerebrovascular Accident Post Recombinant Tissue Plasminogen Activator Therapy

A 59-year-old Hispanic man presented with right upper and lower extremity weakness, associated with facial drop and slurred speech starting 2 hours before the presentation. He denied visual disturbance, headache, chest pain, palpitations, dyspnea, dysphagia, fever, dizziness, loss of consciousness, bowel or urinary incontinence, or trauma. His medical history was significant for uncontrolled type 2 diabetes mellitus, hypertension, hyperlipidemia, and benign prostatic hypertrophy. Social history included cigarette smoking (1 pack per day for 20 years) and alcohol intake of 3 to 4 beers daily. Family history was not significant, and he did not remember his medications. In the emergency department, his vital signs were stable. His physical examination was remarkable for right-sided facial droop, dysarthria, and right-sided hemiplegia. The rest of the examination findings were insignificant. His National Institutes of Health Stroke Scale (NIHSS) score was calculated as 7. Initial CT angiogram of head and neck reported no acute intracranial findings. The neurology team was consulted, and intravenous recombinant tissue plasminogen activator (t-PA) was administered along with high-intensity statin therapy. The patient was admitted to the intensive care unit where his hemodynamics were monitored for 24 hours and later transferred to the telemetry unit. MRI of the head revealed an acute 1.7-cm infarct of the left periventricular white matter and posterior left basal ganglia. How would you manage this case?

This case scenario presents a patient with acute ischemic cerebrovascular accident (CVA) requiring intravenous t-PA. Diagnosis was based on clinical neurologic symptoms and an NIHSS score of 7 and was later confirmed by neuroimaging. He had multiple comorbidities, including hypertension, diabetes, dyslipidemia, and smoking history, which put him at a higher risk for developing cardiovascular disease. Because his symptoms started within 4.5 hours of presentation, he was deemed to be a candidate for thrombolytics. The eligibility time line is estimated either by self-report or last witness of baseline status.

Ischemic strokes are caused by an obstruction of a blood vessel, which irrigates the brain mainly secondary to the development of atherosclerotic changes, leading to cerebral thrombosis and embolism. Diagnosis is made based on presenting symptoms and CT/MRI of the head, and the treatment is focused on cerebral reperfusion based on eligibility criteria and timing of presentation.

Symptoms include alteration of sensorium, numbness, decreased motor strength, facial drop, dysarthria, ataxia, visual disturbance, dizziness, and headache.

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Case Presentation

Statement of ethics, conflict of interest statement, funding sources, author contributions, ischemic stroke in a 29-year-old patient with covid-19: a case report.

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Christian Avvantaggiato , Loredana Amoruso , Maria Pia Lo Muzio , Maria Assunta Mimmo , Michelina Delli Bergoli , Nicoletta Cinone , Luigi Santoro , Lucia Stuppiello , Antonio Turitto , Chiara Ciritella , Pietro Fiore , Andrea Santamato; Ischemic Stroke in a 29-Year-Old Patient with COVID-19: A Case Report. Case Rep Neurol 2 September 2021; 13 (2): 334–340. https://doi.org/10.1159/000515457

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Increasing evidence reports a greater incidence of stroke among patients with Coronavirus disease 2019 (COVID-19) than the non-COVID-19 population and suggests that SARS-CoV-2 infection represents a risk factor for thromboembolic and acute ischemic stroke. Elderly people have higher risk factors associated with acute ischemic stroke or embolization vascular events, and advanced age is strongly associated with severe COVID-19 and death. We reported, instead, a case of an ischemic stroke in a young woman during her hospitalization for COVID-19-related pneumonia. A 29-year-old woman presented to the emergency department of our institution with progressive respiratory distress associated with a 2-day history of fever, nausea, and vomiting. The patient was transferred to the intensive care unit (ICU) where she underwent a tracheostomy for mechanical ventilation due to her severe clinical condition and her very low arterial partial pressure of oxygen. The nasopharyngeal swab test confirmed SARS-CoV-2 infection. Laboratory tests showed neutrophilic leucocytosis, a prolonged prothrombin time, and elevated D-dimer and fibrinogen levels. After 18 days, during her stay in the ICU after suspension of the medications used for sedation, left hemiplegia was reported. Central facial palsy on the left side, dysarthria, and facial drop were present, with complete paralysis of the ipsilateral upper and lower limbs. Computed tomography (CT) of the head and magnetic resonance imaging of the brain confirmed the presence of lesions in the right hemisphere affecting the territories of the anterior and middle cerebral arteries, consistent with ischemic stroke. Pulmonary and splenic infarcts were also found after CT of the chest. The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor. Increased levels of D-dimer and positivity to β2-glycoprotein antibodies could confirm the theory of endothelial activation and hypercoagulability, but other mechanisms – still under discussion – should not be excluded.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, is characterized by a wide range of symptoms, most of which cause acute respiratory distress syndrome [1, 2], associated with intensive care unit (ICU) admission and high mortality [3]. On March 11, 2020, the large global outbreak of the disease led the World Health Organization (WHO) to declare COVID-19 a pandemic, with 11,874,226 confirmed cases and 545,481 deaths worldwide (July 9, 2020) [4]. In many cases, the clinical manifestations of COVID-19 are characteristic of a mild disease that may, however, worsen to a critical lower respiratory infection [2]. At the onset of the disease, the most frequent symptoms are fever, dry cough, fatigue, and shortness of breath as the infection progresses may appear signs and symptoms of respiratory failure that require ICU admission [5, 6]. Although acute respiratory distress syndrome is the most important cause of ICU admission for COVID-19 patients, several studies have underlined the presence of neurological symptoms such as confusion, dizziness, impaired consciousness, ataxia, seizure, anosmia, ageusia, vision impairment, and stroke [7, 8]. In particular, the state of hypercoagulability in patients affected by COVID-19 favors the formation of small and/or large blood clots in multiple organs, including the brain, potentially leading to cerebrovascular disease (ischemic stroke but also intracranial hemorrhage) [9, 10 ].

We found an interesting case of stroke following a SARS-CoV-2 infection in a young patient. A 29-year-old woman, during her ICU hospitalization for COVID-19-related pneumonia, was diagnosed with ischemic stroke of the right hemisphere, without other cardiac/cerebrovascular risk factors except hypertension. The young age of the patient and the absence of higher cerebrovascular risk factors make the present case very interesting as it can help demonstrate that COVID-19 is an independent risk factor for acute ischemic stroke. In a case series of 214 patients with COVID-19 (mean [SD] age, 52.7 [15.5] years), neurologic symptoms were more common in patients with severe infection who were older than the others [ 11 ]. New-onset CVD was more common in COVID-19 patients who had underlying cerebrovascular risk factors, such as older age (>65 years) [ 12 ], and very few cases of stroke in patients younger than 50 years have been reported [ 12, 13 ]. Our case seems to be the only one younger than 30 years.

On the night between March 19 and 20, 2020, a 29-year-old woman was referred to our hospital “Policlinico Riuniti di Foggia” due to a progressive respiratory distress associated with a 2-day history of fever, nausea, and vomiting. At presentation, the heart rate was 128 bpm, the blood oxygen saturation measured by means of the pulse oximeter was 27%, the respiratory rate was 27 breaths per minute, and the blood pressure was 116/77 mm Hg. The arterial blood gas test showed a pH of 7.52, pO 2 20 mm Hg, and pCO 2 34 mm Hg. The patient was immediately transferred to the ICU where she underwent tracheostomy and endotracheal intubation for mechanical ventilation due to her severe clinical condition and deteriorated pulmonary gas exchange. The diagnosis of COVID-19 was confirmed by PCR on a nasopharyngeal swab.

The family medical history was normal, and the only known pre-existing medical conditions were polycystic ovary syndrome (diagnosed 3 years earlier), conversion disorder, and hypertension (both diagnosed 2 years earlier). Ramipril and nebivolol were prescribed for the high blood pressure treatment, and sertraline was prescribed for the conversion disorder treatment. Drug therapy adherence was inconstant. The patient had no history of diabetes, cardiac pathologies, strokes, transient ischemic attacks, thromboembolic, or other vascular pathologies.

Laboratory tests showed neutrophilic leukocytosis (white blood cell count 14.79 × 10 3 , neutrophil percentage 89.8%, and neutrophil count 13.29 × 10 3 ), a prolonged prothrombin time (15.3 s) with a slightly elevated international normalized ratio (1.38), and elevated D-dimer (6,912 ng/mL) and fibrinogen levels (766 mg/dL). Other findings are shown in Table  1 .

Laboratory test

This pharmacological therapy was set as follows: enoxaparin 6,000 U.I. once a day, piperacillin 4 g/tazobactam 0.5 g twice a day; Kaletra, a combination of lopinavir and ritonavir indicated for human immunodeficiency virus (HIV) infection treatment, 2 tablets twice a day; hydroxychloroquine 200 mg once a day; and furosemide 250 mg, calcium gluconate, and aminophylline 240 mg 3 times a day. No adverse events were reported.

On April 7, 2020, during her stay in the ICU and after suspension of the medications used for sedation, left hemiplegia was reported. The same day, the patient underwent a computed tomography examination of the head, which showed areas of hypodensity in the right hemisphere due to recent cerebral ischemia.

On April 16, 2020, the patient was oriented to time, place, and person. Central facial palsy on the left side, dysarthria, and facial drop were present, with complete paralysis of the ipsilateral upper and lower limbs. The power of all the muscles of the left limbs was grade 0 according to the Medical Research Council (MRC) scale. Deep tendon reflexes were reduced on the left upper limb but hyperactive on the ipsilateral lower limb, with a slight increase in the muscle tonus. The senses of touch, vibration, and pain were reduced on the left side of the face and body.

On the same day, the patient underwent magnetic resonance imaging (MRI) of the brain (Fig.  1 a), showing lesions on the right hemisphere affecting the territories of the anterior and middle cerebral arteries. On May 5, 2020, magnetic resonance angiography showed an early duplication of the sphenoidal segment of the right middle cerebral artery, the branches of which are irregular with rosary bead-like aspects (Fig.  1 d, e); on the same day, the second MRI (Fig.  1 b) confirmed the lesions. Computed tomography of the chest (Fig.  1 c) and abdomen (Fig.  1 f), performed 5 days after the MRI of the brain, showed not only multifocal bilateral ground-glass opacities but also a basal subpleural area of increased density within the left lung (4 × 4 × 3 cm), consistent with a pulmonary infarction. In addition, a vascular lesion, consistent with a splenic infarct, was found in the inferior pole of the spleen. Doppler echocardiography of the hearth showed regular right chambers and left atrium and a slightly hypertrophic left ventricle with normal size and kinetics (ejection fraction: 55%). The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor.

Imaging. a April 16, 2020; MRI of the brain: lesions in the right hemisphere affecting the territories of the anterior and the middle cerebral arteries. b May 5, 2020; MRI of the brain: same lesions in the right hemisphere shown in the previous image. d , e May 5, 2020; MRA showed an early duplication of the sphenoidal segment of the right middle cerebral artery, the branches of which are irregular with rosary bead-like aspect and reduction of blood flow in the middle cerebral artery. c April 20, 2020; CT of the abdomen: vascular lesion, consistent with a splenic infarct, found in the inferior pole of the spleen. f April 20, 2020; CT of the chest: basal subpleural area of increased density within the left lung (4 × 4 × 3 cm), consistent with a pulmonary infarction. MRA, magnetic resonance angiography; CT, computed tomography; MRI, magnetic resonance imaging.

The pandemic outbreak of novel SARS-CoV-2 infection has caused great concern among the services and authorities responsible for public health due to not only the mortality rate but also the danger of filling up hospital capacities in terms of ICU beds and acute non-ICU beds. In this regard, the nonrespiratory complications of COVID-19 should also be taken into great consideration, especially those that threaten patients’ lives and extend hospitalization times. Stroke is one of these complications, since a greater incidence of stroke among patients with COVID-19 than the non-COVID-19 population has been reported, and a preliminary case-control study demonstrated that SARS-CoV-2 infection represents a risk factor for acute ischemic stroke [ 14 ].

We found that the reported case is extremely interesting, since the woman is only 29 years old and considering how stroke in a young patient without other known risk factors is uncommon. Not only elderly people have higher risk factors associated with acute ischemic stroke or embolization vascular events [ 15 ], but it is also true that advanced age is strongly associated with severe COVID-19 and death. The severity of the disease is directly linked to immune dysregulation, cytokine storm, and acute inflammation state, which in turn are more common in patients who present immunosenescence [6].

Inflammation plays an important role in the occurrence of cardiovascular and cerebrovascular diseases since it favors atherosclerosis and affects plaque stability [ 16 ]. The ischemic stroke of the 29-year-old woman does not appear to be imputable to emboli originating a pre-existing atheromatous plaque, both for the age of the patient and for the absence of plaques at the Doppler ultrasound study of the supra-aortic trunks.

Most likely, COVID-19-associated hypercoagulability and endothelial dysfunction are the causes of ischemic stroke, as suggested by other studies and case reports [ 10, 13, 17 ]. Although the mechanisms by which SARS-CoV-2 infection leads to hypercoagulability are still being studied, current knowledge suggests that cross talk between inflammation and thrombosis has a crucial role [ 18 ]. The release of inflammatory cytokines leads to the activation of epithelial cells, monocytes, and macrophages. Direct infection of endothelial cells through the ACE2 receptor also leads to endothelial activation and dysfunction, expression of tissue factor, and platelet activation and increased levels of VWF and FVIII, all of which contribute to thrombin generation and fibrin clot formation [ 17 ]. The 29-year-old patient showed an increased level of D-dimer, which is a degradation product of cross-linked fibrin, indicating a global activation of hemostasis and fibrinolysis and conforming to the hypothesis of COVID-19-associated hypercoagulability. Endothelial activation and hypercoagulability are also confirmed by positivity to β2 glycoprotein antibodies. Anticardiolipin antibody and/or β2 glycoprotein antibody positivity has been reported in a few studies [ 17, 19, 20 ]. In addition, widespread thrombosis in SARS-CoV-2 infection could also be caused by neutrophil extracellular traps (NETs). Neutrophilia [ 21 ] and an elevated neutrophil-lymphocyte ratio [ 22 ] have been reported by numerous studies as predictive of worse disease outcomes, and recently, the contribution of NETs in the pathophysiology of COVID-19 was reported [ 23 ]. Thrombogenic involvement of NETs has been described in various settings of thrombosis, including stroke, myocardial infarction, and deep vein thrombosis [ 24 ]. The high neutrophil count found in our case does not exclude the hypothesis that NETs are involved in the pathogenesis of ischemic stroke.

Ischemic stroke in young patients without pre-existing cerebrovascular risk factors is very unusual. In this regard, our case of an ischemic stroke, reported in a 29-year-old woman, is very interesting. Although it is not possible to determine precisely when the thromboembolic event occurred, our case of stroke during COVID-19-related pneumonia seems to confirm that COVID-19 is an independent risk factor for acute ischemic stroke. The mechanisms by which coronavirus disease leads to stroke are still under study, but it is clear that hypercoagulability and endothelial activation play a key role. Testing for SARS-CoV-2 infection should be considered for patients who develop neurologic symptoms, but it is equally important to monitor COVID-19 patients during their hospitalization to find any neurological sign or symptom in a timely manner. Our case suggests that discovering neurological deficits in sedated patients promptly can be very difficult; for this reason, sedation in mechanically ventilated patients has to be considered only if strictly necessary. Performing serial laboratory testing and waking up the patient as soon as clinical conditions allow are strategies that should be taken into account.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor-in-chief of this journal.

The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

No funding was received for the publication of this case report.

All authors agree with the contents of the manuscript and were fully involved in the study and preparation of the manuscript. All authors read and approved the final version of the manuscript. M.A. Mimmo, M.P. Lo Muzio, M. Delli Bergoli, and L. Amoruso collected the data. C. Avvantaggiato wrote the manuscript with support of N. Cinone, L. Santoro, and C. Ciritella. C. Avvantaggiato, A. Turitto, and L. Stuppiello researched and discussed the neurophysiological principles of this study. P. Fiore and A. Santamato supervised the project.

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• Published: August 2007

A case of acute ischemic stroke: optimizing management with penumbra and vessel imaging

• Brian H Buck 1 &
• Jeffrey L Saver 2  

Nature Clinical Practice Neurology volume  3 ,  pages 465–469 ( 2007 ) Cite this article

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Background An 83-year-old woman with a history of hypertension and dyslipidemia developed acute onset of impaired speech and comprehension, and right-sided weakness. Her previous medical history was notable for hyperthyroidism and a curative remote mastectomy for breast cancer. The patient was on two antihypertensive medications and a statin, and she was not receiving any antiplatelet medication. She was taken by ambulance to a primary stroke center. Initial examination showed global aphasia, right homonymous hemianopia, right hemiplegia, and hemisensory loss.

Investigations Physical examination, laboratory tests, noncontrast head CT scan, multimodal brain MRI scan, catheter cerebral angiogram, echocardiogram, continuous cardiac monitoring.

Diagnosis Acute ischemic stroke caused by distal left internal carotid artery occlusion, with salvageable penumbral tissue and a persistent large-vessel occlusion.

Management Neuroprotective study agent (total dose of 20 g intravenous MgSO 4 or matched placebo), intravenous tissue plasminogen activator, rescue mechanical thrombectomy using the Merci ® clot retrieval device.

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Acknowledgements

BH Buck is supported by a fellowship award from the Heart and Stroke Foundation of Canada.

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BH Buck is a Fellow of the Division of Neurology in the Department of Medicine, Sunnybrook Health Science Centre, University of Toronto, Toronto, ON, Canada.,

Brian H Buck

JL Saver is Director of the UCLA Stroke Centre and Professor of Neurology at University of California Los Angeles, Los Angeles, CA, USA.,

Jeffrey L Saver

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JL Saver is Principal Investigator of the NIH FAST–MAG Trial, is an investigator in the NIH MR RESCUE, IMS 3 and CLEAR trials, is on the Scientific Advisory Board and Speaker's Bureau for Boehringer Ingelheim (secondary prevention) and has received speaking honoraria from Concentric Medical. BH Buck declared no competing interests.

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Buck, B., Saver, J. A case of acute ischemic stroke: optimizing management with penumbra and vessel imaging. Nat Rev Neurol 3 , 465–469 (2007). https://doi.org/10.1038/ncpneuro0553

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DOI : https://doi.org/10.1038/ncpneuro0553

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Ischemic stroke: A case study

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This presents an analysis of a case of Ischemic stroke in terms of possible etiology, pathophysiology, drug analysis and nursing care

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This case study presents a 68-year old “right-handed” African-American man named Randall Swanson. He has a history of hypertension, hyperlipidemia and a history of smoking one pack per day for the last 20 years. He is prescribed Atenolol for his HTN, and Simvastatin for Hyperlipidemia (but he has a history of not always taking his meds). His father had a history of hypertension and passed away from cancer 10 years ago. His mother has a history of diabetes and is still alive.

Randall was gardening with his wife on a relaxing Sunday afternoon. Out of nowhere, Randall fell to the ground. When his wife rushed to his side and asked how he was doing, he answered with garbled and incoherent speech. It was then that his wife noticed his face was drooping on the right side. His wife immediately called 911 and paramedics arrived within 6 minutes. Upon initial assessment, the paramedics reported that Randall appeared to be experiencing a stroke as he presented with right-sided facial droop and weakness and numbness on the right side of his body. Fortunately, Randall lived nearby a stroke center so he was transported to St. John’s Regional Medical Center within 17 minutes of paramedics arriving to his home.

Initial Managment

Upon arrival to the Emergency Department, the healthcare team was ready to work together to diagnose Randall. He was placed in bed with the HOB elevated to 30 degrees to decrease intracranial pressure and reduce any risks for aspiration. Randall’s wife remained at his side and provided the care team with his brief medical history which as previously mentioned, consists of hypertension, hyperlipidemia and smoking one pack per day for the last 20 years. He had no recent head trauma, never had a stroke, no prior surgeries, and no use of anticoagulation medications.

Physical Assessment

Upon first impression, Nurse Laura recognized that Randall was calm but looked apprehensive. When asked to state his name and date of birth, his speech sounded garbled at times and was very slow, but he could still be understood. He could not recall the month he was born in but he was alert and oriented to person, time, and situation. When asked to state where he was, he could not recall the word hospital. He simply pointed around the room while repeating “here.”

Further assessment revealed that his pupils were equal and reactive to light and that he presented with right-sided facial paralysis. Randall was able to follow commands but when asked to move his extremities, he could not lift his right arm and leg. He also reported that he could not feel the nurse touch his right arm and leg. Nurse Laura gathered the initial vital signs as follows: BP: 176/82, HR: 93, RR: 20, T:99.4, O2: 92% RA and a headache with pain of 3/10.

Doctor’s Orders

The doctor orders were quickly noted and included:

-2L O2 (to keep O2 >93%)

– 500 mL Bolus NS

– VS Q2h for the first 8 hrs.

-Draw labs for: CBC, INR, PT/INR, PTT, and Troponin

-Get an EKG

-Chest X ray

-Glucose check

-Obtain patient weight

-Perform a National Institute of Health Stroke Scale (also known as NIHSS) Q12h for the first 24 hours, then Q24h until he is discharged

-Notify pharmacy of potential t-PA preparation.

Nursing Actions

Nurse Laura started an 18 gauge IV in Randall’s left AC and started him on a bolus of 500 mL of NS. A blood sample was collected and quickly sent to the lab. Nurse Laura called the Emergency Department Tech to obtain a 12 lead EKG.

Pertinent Lab Results for Randall

The physician and the nurse review the labs:

WBC 7.3 x 10^9/L

RBC 4.6 x 10^12/L

Plt 200 x 10^9/L

LDL 179 mg/dL

HDL 43 mg/dL

Troponin <0.01 ng/mL

EKG and Chest X Ray Results

The EKG results and monitor revealed Randall was in normal sinus rhythm; CXR was negative for pulmonary or cardiac pathology

CT Scan and NIHSS Results 

The NIH Stroke Scale was completed and demonstrated that Randall had significant neurological deficits with a score of 13. Within 20 minutes of arrival to the hospital, Randall had a CT-scan completed. Within 40 minutes of arrival to the hospital, the radiologist notified the ED physician that the CT-scan was negative for any active bleeding, ruling our hemorrhagic stroke.

The doctors consulted and diagnosed Randall with a thrombotic ischemic stroke and determined that that plan would include administering t-PA. Since Randall’s CT scan was negative for a bleed and since he met all of the inclusion criteria he was a candidate for t-PA. ( Some of the inclusion criteria includes that the last time the patient is seen normal must be within 3 hours, the CT scan has to be negative for bleeding, the patient must be 18 years or older, the doctor must make the diagnosis of an acute ischemic stroke, and the patient must continue to present with neurological deficits.)

Since the neurologist has recommended IV t-PA, the physicians went into Randall’s room and discussed what they found with him and his wife. Nurse Laura answered and addressed any remaining concerns or questions.

Administration

Randall and his wife decided to proceed with t-PA therapy as ordered, therefore Nurse Laura initiated the hospital’s t-PA protocol. A bolus of 6.73 mg of tPA was administered for 1 minute followed by an infusion of 60.59 mg over the course of 1 hour. ( This was determined by his weight of 74.8 kg).  After the infusion was complete, Randall was transferred to the ICU for close observation. Upon reassessment of the patient, Randall still appeared to be displaying neurological deficits and his right-sided paralysis had not improved. His vital signs were assessed and noted as follows: BP: 149/79 HR: 90 RR: 18 T:98.9 O2: 97% 2L NC Pain: 2/10.

Randall’s wife was crying and he appeared very scared, so Nurse John tried to provide as much emotional support to them as possible. Nurse John paid close attention to Randall’s blood pressure since he could be at risk for hemorrhaging due to the medication. Randall was also continually assessed for any changes in neurological status and allergic reactions to the t-PA. Nurse John made sure that Stroke Core Measures were followed in order to enhance Randall’s outcome.

In the ICU, Randall’s neurological status improved greatly. Nurse Jan noted that while he still garbled speech and right-sided facial droop, he was now able to recall information such as his birthday and he could identify objects when asked. Randall was able to move his right arm and leg off the bed but he reported that he was still experiencing decreased sensation, right-sided weakness and he demonstrated drift in both extremities.

The nurse monitored Randall’s blood pressure and noted that it was higher than normal at 151/83. She realized this was an expected finding for a patient during a stroke but systolic pressure should be maintained at less than 185 to lower the risk of hemorrhage. His vitals remained stable and his NIHSS score decreased to an 8. Labs were drawn and were WNL with the exception of his LDL and HDL levels. His vital signs were noted as follows: BP 151/80 HR 92 RR 18 T 98.8 O2 97% RA Pain 0/10

The Doctor ordered Physical, Speech, and Occupational therapy, as well as a swallow test.

Swallowing Screen

Randall remained NPO since his arrival due to the risks associated with swallowing after a stroke. Nurse Jan performed a swallow test by giving Randall 3 ounces of water. On the first sip, Randall coughed and subsequently did not pass. Nurse Jan kept him NPO until the speech pathologist arrived to further evaluate Randall. Ultimately, the speech  pathologist determined that with due caution, Randall could be put on a dysphagia diet that featured thickened liquids

Physical Therapy & Occupational Therapy

A physical therapist worked with Randall and helped him to carry out passive range of motion exercises. An occupational therapist also worked with Randall to evaluate how well he could perform tasks such as writing, getting dressed and bathing. It was important for these therapy measures to begin as soon as possible to increase the functional outcomes for Randall. Rehabilitation is an ongoing process that begins in the acute setting.

Day 3- third person 

During Day 3, Randall’s last day in the ICU, Nurse Jessica performed his assessment. His vital signs remained stable and WNL as follows: BP: 135/79 HR: 90 RR: 18 T: 98.9 O2: 97% on RA, and Pain 0/10. His NIHSS dramatically decreased to a 2. Randall began showing signs of improved neurological status; he was able to follow commands appropriately and was alert and oriented x 4. The strength  in his right arm and leg markedly improved. he was able to lift both his right arm and leg well and while he still reported feeling a little weakness and sensory loss, the drift in both extremities was absent.

Rehabilitation Therapies

Physical, speech, and occupational therapists continued to work with Randall. He was able to call for assistance and ambulate with a walker to the bathroom and back. He was able to clean his face with a washcloth, dress with minimal assistance, brush his teeth, and more. Randall continued to talk with slurred speech but he was able to enunciate with effort.

On day 4, Randall was transferred to the med-surg floor to continue progression. He continued to work with physical and occupational therapy and was able to perform most of his ADLs with little assistance. Randall could also ambulate 20 feet down the hall with the use of a walker.

Long-Term Rehabilitation and Ongoing Care

On day 5, Randall was discharged to a rehabilitation facility and continued to display daily improvement. The dysphagia that he previously was experiencing resolved and he was discharged home 1.5 weeks later. Luckily for Randall, his wife was there to witness his last known well time and she was able to notify first responders. They arrived quickly and he was able to receive t-PA in a timely manner. With the help of the interdisciplinary team consisting of nurses, therapists, doctors, and other personnel, Randall was put on the path to not only recover from the stroke but also to quickly regain function and quality of life very near to pre-stroke levels. It is now important that Randall continues to follow up with his primary doctor and his neurologist and that he adheres to his medication and physical therapy regimen.

Case Management

During Randall’s stay, Mary the case manager played a crucial role in Randall’s path to recovery. She determined that primary areas of concern included his history of medical noncompliance and unhealthy lifestyle. The case manager consulted with Dietary and requested that they provide Randall with education on a healthy diet regimen. She also provided him with smoking cessation information. Since Randall has been noncompliant with his medications, Mary determined that social services should consult with him to figure out what the reasons were behind his noncompliance. Social Services reported back to Mary that Randall stated that he didn’t really understand why he needed to take the medication. It was apparent that he had not been properly educated. Mary also needed to work with Randall’s insurance to ensure that he could go to the rehab facility as she knew this would greatly impact his ultimate outcome. Lastly, throughout his stay, the case manager provided Randall and his wife with resources on stroke educational materials. With the collaboration of nurses, education on the benefits of smoking cessation, medication adherence, lifestyle modifications, and stroke recognition was reiterated to the couple. After discharge, the case manager also checked up with Randall to make sure that he complied with his follow up appointments with the neurologist and physical and speech therapists,

• What risk factors contributed to Randall’s stroke?
• What types of contraindications could have prevented Randall from receiving t-PA?
• What factors attributed to Randall’s overall favorable outcome?

Nursing Case Studies by and for Student Nurses Copyright © by jaimehannans is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study

Collaborators.

• INTERSTROKE investigators : M O'Donnell ,  D Xavier ,  S Yusuf ,  S Rangarajan ,  S Islam ,  P Rao-Melacini ,  S L Chin ,  J DeJesus ,  S Agapay ,  J Kaszyca ,  M Dehghan ,  M McQueen ,  K Hall ,  J Keys ,  X Wang ,  A Hosangadi ,  R Diaz ,  L Sposato ,  C Bahit ,  M Bianchi ,  A Pascual ,  M E Martin ,  P Schygiel ,  G Falcone ,  M Garrote ,  J Varigos ,  G Hankey ,  A Claxton ,  W Y Wang ,  A Avezum ,  I Santos ,  M P Pereira ,  R Nakamura ,  K Takeuti ,  L Avezum ,  S Faria ,  M Teixeira ,  A Gaffga ,  H Reis ,  A Lameira ,  M Friedrich ,  L C Marrone ,  J F K Saraiva ,  A C Carvalho ,  I Rocha ,  V L Laet ,  M Coutinho ,  F Brunel ,  L Melges ,  C R Garbelini ,  A C Baruzzi ,  D A Reis ,  M O'Donnell ,  S Yusuf ,  S Ounpuu ,  M K Kapral ,  J DeJesus ,  D Gladstone ,  G Valencia ,  P Teal ,  A Woolfendan ,  P Masigan ,  K Murray ,  J Sancan ,  A Shuaib ,  B Schwindt ,  F Silver ,  M Sharma ,  M Mortensen ,  F Lanas ,  S Saavera ,  L Liu ,  H Zhang ,  X Wang ,  W Wang ,  J Li ,  L Liu ,  Y Sun ,  J Chen ,  L Zhou ,  W Jia ,  Z Zhang ,  J Lv ,  C Zhang ,  G Chen ,  H Wang ,  L Liu ,  Y Zhang ,  Y Chen ,  H Zheng ,  Y Zhang ,  J Wang ,  J Huang ,  Z Deng ,  W Zhang ,  W Li ,  S Jia ,  J Wang ,  L Wang ,  J Wang ,  J Shi ,  W Gu ,  H Shao ,  Y Hu ,  H Song ,  R Ji ,  L Hao ,  J Zhang ,  F Hou ,  D Wang ,  J Li ,  L Meng ,  L Duan ,  P L Jaramillo ,  G Sanchez ,  R Garcia ,  J Arguello ,  N Ruiz ,  D I Molina ,  A Sotomayor ,  K Sotomayor ,  M Suarez ,  Z Rumboldt ,  I Lusic ,  T Truelsen ,  H K Iversen ,  C Back ,  M M Petersen ,  E Panaherrera ,  Y C Duarte ,  S Caceres ,  C Weimar ,  A J Grau ,  B Bode ,  J Roether ,  H Wuttig ,  K Busch ,  P Pais ,  D Xavier ,  A Sigamani ,  N P Mathur ,  P Rahul ,  D Rai ,  A K Roy ,  G R K Sarma ,  T Mathew ,  G Kusumkar ,  K A Salam ,  U Karadan ,  L Achambat ,  Y Singh ,  J D Pandian ,  R Verma ,  V Atam ,  A Agarwal ,  N Chidambaran ,  R Umarani ,  S Ghanta ,  G K Babu ,  G Sathyanarayana ,  G Sarada ,  S Navya Vani ,  R Sundararajan ,  S S Sivakumar ,  R S Wadia ,  S Bandishti ,  R Gupta ,  R R Agarwal ,  I Mohan ,  S Joshi ,  S Kulkarni ,  S Parthasaradhi ,  P Joshi ,  M Pandharipande ,  N Badnerkar ,  R Joshi ,  S P Kalantri ,  S Somkuwar ,  S Chavhan ,  H Singh ,  S Varma ,  H Singh ,  G K Sidhu ,  R Singh ,  K L Bansal ,  A Bharani ,  S Pagare ,  A Chouhan ,  B N Mahanta ,  T G Mahanta ,  G Rajkonwar ,  S K Diwan ,  S N Mahajan ,  P Shaikh ,  S Oveisgharan ,  R Kelishadi ,  A Bahonar ,  N Mohammadifard ,  H Heidari ,  A Dehghani ,  S A Mousavi ,  O Albaker ,  K Yusoff ,  A Chandramouli ,  N Syuhadamohd ,  A Damasceno ,  S Loureiro ,  O S Ogah ,  A Ogunniyi ,  R Akinyemi ,  M Owolabi ,  A Oguunniyi ,  I O Onwuekwe ,  S Mahmoud ,  L Owolabi ,  G Malaga ,  Z Salazar ,  P Ponce de Leaon ,  E Najar ,  M Aphang ,  A L Dans ,  M V Sulit ,  E Collantes ,  M del Castillo ,  D Morales ,  C Lagayan ,  M Candela ,  A Roxas ,  I Tan ,  C Recto ,  G Lau ,  A Czlonkowska ,  D Ryglewicz ,  M Skowronska ,  M Restel ,  A Bochynska ,  K Chwojnicki ,  M Kubach ,  A Stowik ,  M Wnuk ,  L DeVilliers ,  B Mayosi ,  D Magazi ,  A S A Elsayed ,  A Bukhari ,  Z Sawaraldahab ,  H Hamad ,  M El Taher ,  A Abdelhameed ,  M Alawad ,  D Alkabashi ,  H Alsir ,  A Rosengren ,  M Andreasson ,  B Cederin ,  C Schander ,  A C Elgasen ,  E Bertholds ,  K Bengtasson ,  Y Nilanont ,  N Samart ,  T Pyatat ,  N Prayoonwiwat ,  N Phongwarin ,  N C Suwanwela ,  S Tiamkao ,  R Tulyapronchote ,  S Boonyakarnkul ,  S Hanchaiphiboolkul ,  S Muengtaweepongsa ,  K Watcharasakslip ,  P Sathirapanya ,  P Pleumpanupat ,  A Oguz ,  A A K Akalin ,  C Mondo ,  J Kayima ,  M Nakisige ,  S Kitoleeko ,  P Byanyima ,  P Langhorne ,  R Sacco ,  L Hilbrich

Affiliation

• 1 Population Health Research Institute, McMaster University, Hamilton, ON, Canada. [email protected]
• PMID: 20561675
• DOI: 10.1016/S0140-6736(10)60834-3

Background: The contribution of various risk factors to the burden of stroke worldwide is unknown, particularly in countries of low and middle income. We aimed to establish the association of known and emerging risk factors with stroke and its primary subtypes, assess the contribution of these risk factors to the burden of stroke, and explore the differences between risk factors for stroke and myocardial infarction.

Methods: We undertook a standardised case-control study in 22 countries worldwide between March 1, 2007, and April 23, 2010. Cases were patients with acute first stroke (within 5 days of symptoms onset and 72 h of hospital admission). Controls had no history of stroke, and were matched with cases for age and sex. All participants completed a structured questionnaire and a physical examination, and most provided blood and urine samples. We calculated odds ratios (ORs) and population-attributable risks (PARs) for the association of all stroke, ischaemic stroke, and intracerebral haemorrhagic stroke with selected risk factors.

Findings: In the first 3000 cases (n=2337, 78%, with ischaemic stroke; n=663, 22%, with intracerebral haemorrhagic stroke) and 3000 controls, significant risk factors for all stroke were: history of hypertension (OR 2.64, 99% CI 2.26-3.08; PAR 34.6%, 99% CI 30.4-39.1); current smoking (2.09, 1.75-2.51; 18.9%, 15.3-23.1); waist-to-hip ratio (1.65, 1.36-1.99 for highest vs lowest tertile; 26.5%, 18.8-36.0); diet risk score (1.35, 1.11-1.64 for highest vs lowest tertile; 18.8%, 11.2-29.7); regular physical activity (0.69, 0.53-0.90; 28.5%, 14.5-48.5); diabetes mellitus (1.36, 1.10-1.68; 5.0%, 2.6-9.5); alcohol intake (1.51, 1.18-1.92 for more than 30 drinks per month or binge drinking; 3.8%, 0.9-14.4); psychosocial stress (1.30, 1.06-1.60; 4.6%, 2.1-9.6) and depression (1.35, 1.10-1.66; 5.2%, 2.7-9.8); cardiac causes (2.38, 1.77-3.20; 6.7%, 4.8-9.1); and ratio of apolipoproteins B to A1 (1.89, 1.49-2.40 for highest vs lowest tertile; 24.9%, 15.7-37.1). Collectively, these risk factors accounted for 88.1% (99% CI 82.3-92.2) of the PAR for all stroke. When an alternate definition of hypertension was used (history of hypertension or blood pressure >160/90 mm Hg), the combined PAR was 90.3% (85.3-93.7) for all stroke. These risk factors were all significant for ischaemic stroke, whereas hypertension, smoking, waist-to-hip ratio, diet, and alcohol intake were significant risk factors for intracerebral haemorrhagic stroke.

Interpretation: Our findings suggest that ten risk factors are associated with 90% of the risk of stroke. Targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the burden of stroke.

Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Pfizer Cardiovascular Award, Merck, AstraZeneca, and Boehringer Ingelheim.

Copyright 2010 Elsevier Ltd. All rights reserved.

Publication types

• Multicenter Study
• Research Support, Non-U.S. Gov't
• Atrial Fibrillation / complications
• Brain Ischemia / complications*
• Case-Control Studies
• Cerebral Hemorrhage / complications*
• Developed Countries
• Developing Countries
• Hypertension / complications
• Middle Aged
• Myocardial Infarction / epidemiology
• Myocardial Infarction / etiology
• Risk Factors
• Stroke / epidemiology
• Stroke / etiology*
• Waist-Hip Ratio

Grants and funding

• Canadian Institutes of Health Research/Canada

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Vagus Nerve Stimulation in Ischemic Stroke

• Published: 27 November 2023
• Volume 23 , pages 947–962, ( 2023 )

Cite this article

• Sasan Andalib 1 , 2 ,
• Afshin A. Divani 3 ,
• Cenk Ayata 4 ,
• Sheharyar Baig 5 ,
• Ethem Murat Arsava 6 ,
• Mehmet Akif Topcuoglu 6 ,
• Eder Leonardo Cáceres 7 ,
• Vinay Parikh 8 ,
• Masoom J. Desai 3 ,
• Arshad Majid 5 ,
• Sara Girolami 9 &
• Mario Di Napoli 9  

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Purpose of Review

Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms.

Recent Findings

Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery.

The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.

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NOn-invasive Vagus nerve stimulation in acute Ischemic Stroke (NOVIS): a study protocol for a randomized clinical trial

Anne van der Meij, Marianne A. A. van Walderveen, … Marieke J. H. Wermer

Effects and safety of vagus nerve stimulation on upper limb function in patients with stroke: a systematic review and meta-analysis

Auwal Abdullahi, Thomson W. L. Wong & Shamay S. M. Ng

Optimizing Dosing of Vagus Nerve Stimulation for Stroke Recovery

David T. Pruitt, Tanya T. Danaphongse, … Seth A. Hays

Data Availability

Not applicable.

Abbreviations

Auricular branch of the vagus nerve

Acute ischemic stroke

• Blood–brain barrier

Brain-derived neurotrophic factor

• Cortical spreading depolarization

Food and Drug Administration

Growth differentiation factor 11

Intracerebral hemorrhage

• Locus coeruleus

Light chain 3

Lipocalin-type prostaglandin D synthase

Interleukin

Middle cerebral artery occlusion

Modified Rankin scale

National Institute of Health stroke scale

• Nucleus tractus solitarius
• Non-invasive vagus nerve stimulation

Peroxisome proliferator-activated receptor-gamma

Recombinant IL-17A

• Traumatic brain injury

Transcutaneous auricular vagus nerve stimulation

Transcutaneous cervical vagus nerve stimulation

Vascular endothelial growth factor

Vagus nerve stimulation

α7 Nicotinic acetylcholine receptor subunit

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Sasan Andalib

Department of Neurology, Odense University Hospital, Odense, Denmark

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Afshin A. Divani & Masoom J. Desai

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Sasan Andalib, Cenk Ayata, Ethem Murat Arsava, Mehmet Akif Topcuoglu, Eder Leonardo Cáceres, Vinay Parikh, Masoom J Desai, Sara Girolami, and Mario Di Napoli each declare no potential conflicts of interest.

Afshin A. Divani is supported by the National Institute of Neurological Disorders and Stroke (NINDS) grant # 1R21NS130423-01.

Sheharyar Baig is supported by the Association of British Neurologists Clinical Research Training Fellowship (co-funded by the Stroke Association and Berkeley Foundation). Sheharyar Baig and Arshad Majid are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre, Sheffield, England. The expressed views are those of the authors and not necessarily those of the NINDS, the National Health Service (NHS), the NIHR, or the Department of Health and Social Care (DHSC).

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Andalib, S., Divani, A.A., Ayata, C. et al. Vagus Nerve Stimulation in Ischemic Stroke. Curr Neurol Neurosci Rep 23 , 947–962 (2023). https://doi.org/10.1007/s11910-023-01323-w

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Published : 27 November 2023

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DOI : https://doi.org/10.1007/s11910-023-01323-w

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DOACs for Stroke Prevention in Device-Detected AF

Quick Takes

• Two trials compared direct oral anticoagulants (DOACs) to either aspirin or placebo for patients with subclinical AF.
• DOAC therapy was associated with a reduction in ischemic stroke and a composite of thrombotic complications.
• DOAC therapy did not reduce mortality and was associated with an increased risk of major bleeding.

Study Questions:

Is oral anticoagulation effective and safe for patients with device-detected subclinical atrial fibrillation (AF)?

The authors performed a systematic review of randomized trials comparing oral anticoagulation with antiplatelet or not antithrombotic therapy in adults with device-detected AF recorded by a pacemaker, implantable cardioverter-defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. The primary efficacy outcome was ischemic stroke with a secondary outcome as the composite of cardiovascular (CV) death, all-cause stroke, peripheral artery embolization, myocardial infarction, or pulmonary embolism. The primary safety outcome was major bleeding defined by the International Society on Thrombosis and Hemostasis criteria.

The authors identified two randomized trials inclusive of 6,548 patients (NOAH-AFNET 6 and ARTESiA) comparing either edoxaban or apixaban compared to aspirin or placebo. Included patients were at moderate to high risk of stroke (median CHA 2 DS 2 -VASc score 3.9-4) with a median duration of device-detected AF of 1.5-2.8 hours. Use of direct oral anticoagulation (DOAC) was associated with a reduction in the risk of ischemic stroke (relative risk [RR], 0.68; 95% confidence interval [CI], 0.50-0.92) and the composite of thrombotic outcomes (RR, 0.85; 95% CI, 0.73-0.99). There was no reduction in the risk of CV death (RR, 0.95; 95% CI, 0.76-1.17). Oral anticoagulant use was associated with an increased risk of major bleeding (RR, 1.62; 95% CI, 1.05-2.50).

Conclusions:

The authors conclude that the NOAH-AFNET 6 and ARTESiA trials are consistent with each other—associated with a reduction in ischemic stroke and an increase in the risk of major bleeding.

Perspective:

Clinicians are increasingly facing the difficult task of determining if subclinical AF should receive the same stroke prevention treatment efforts as patients with clinical AF. Widespread use of implanted cardiac devices often detect runs of AF that are asymptomatic. These two randomized trials demonstrate that in a population of patients at moderate to high risk of stroke, use of DOACs is associated with a reduction in the subsequent risk of stroke as compared to aspirin or placebo when subclinical AF is detected. However, that benefit is offset by a notable 60% increased risk of major bleeding. Notably, use of anticoagulation was not associated with a reduction in CV death across the two trials. For clinicians trying to determine if oral anticoagulant should be prescribed for their patients with subclinical AF, longer durations (>2-4 hours) and higher baseline stroke risk (CHA 2 DS 2 -VASc score ≥4) may be populations best to target with this therapy, as long as the bleeding risk is not prohibitively high.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Atrial Fibrillation, Stroke

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New-onset acute ischemic stroke following COVID-19: A case–control study

Fariborz khorvash.

1 Department of Neurology, Al Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

Mohammad Amin Najafi

Mohsen kheradmand, mohammad saadatnia, rojin chegini.

2 Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Farideh Najafi

3 Department of Orthopedic, Rothman Institute, Thomas Jefferson University, Philadelphia, Pennsylvania

Background:

Neurological manifestations of coronavirus disease 2019 (COVID-19) have been highlighted. COVID-19 potentially increases the risk of thromboembolism. We aimed to compare patients with COVID-19 with and without new-onset acute ischemic stroke (AIS).

Materials and Methods

In this single-center retrospective case–control study, demographics, clinical characteristics, laboratory findings, and clinical outcomes were compared between 51 patients with both COVID-19 and AIS (group A) and 160 patients with COVID-19 and without AIS (group B).

Patients in group A were significantly older, more likely to present with critical COVID-19 ( P = 0.004), had higher rates of admission in the intensive care unit ( P < 0.001), more duration of hospitalization ( P < 0.001), and higher in-hospital mortality ( P < 0.001). At the time of hospitalization, O 2 saturation ( P = 0.011), PH ( P = 0.04), and HCO3 ( P = 0.005) were lower in group A. White blood cell count ( P = 0.002), neutrophil count ( P < 0.001), neutrophil-lymphocyte ratio ( P = 0.001), D-Dimer ( P < 0.001), blood urea nitrogen (BUN) ( P < 0.001), and BUN/Cr ratio ( P < 0.001) were significantly higher in patients with AIS.

Conclusion:

Stroke in COVID-19 is multifactorial. In addition to conventional risk factors of ischemic stroke (age and cardiovascular risk factors), we found that patients with more severe COVID-19 are more prone to ischemic stroke. Furthermore, leukocyte count, neutrophil count, neutrophil-lymphocyte ratio, D-Dimer, BUN, and BUN/Cr ratio were higher in patients with AIS following COVID-19 infection.

INTRODUCTION

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global concern and causes different clinical characteristics and complications; Neurologic manifestations have been highlighted in numerous studies.[ 1 ]

Previous studies reported that infectious agents increase the risk of ischemic stroke due to the prothrombotic effect of the inflammatory response, thus according to hypercoagulopathy state and the increase of thrombotic events in COVID-19 infection, the increased risk of stroke could be predicted.[ 2 ]

The literature is increasingly being focused on acute ischemic stroke (AIS) characteristics following COVID-19 infection.[ 3 , 4 , 5 , 6 ] Studying the characteristics of stroke in patients with both COVID-19 and stroke may help to better understand the relation between these two diseases. The aim of this study is to compare clinical characteristics, laboratory data, and comorbidities between patients with COVID-19 with and without new-onset AIS.

MATERIALS AND METHODS

This was a single-center retrospective case–control study between October 22, and December 1, 2020. Fifty-one patients with confirmed COVID-19 and new-onset AIS were admitted to the Al Zahra Hospital (group A). One hundred and sixty-one confirmed COVID-19 patients, hospitalized in the same period in our center, were randomly selected as the control group (group B). Patients gave informed consent before take part in this trial. All patients tested positive for SARS-CoV-2 reverse transcription-polymerase chain reaction, had respiratory symptoms, had viral pneumonia findings on chest computed tomography (CT). AIS was diagnosed according to clinical symptoms and imaging studies (brain CT scan or Magnetic resonance imaging). The severity of the disease was determined according to the COVID-19 Treatment Guidelines Panel, which describes critical COVID as “patients with respiratory failure, multiple organ dysfunction, and septic shock.”

Demographic characteristics, patient's medical history, duration of hospitalization (ward or intensive care unit [ICU]), mortality rate, vital signs in admission, baseline laboratory findings, and pulmonary thromboembolism (PTE) rate were extracted from electronic medical records and compared between two groups.

Statistical analysis

Statistical analyses were carried out using the SPSS (SPSS statistic package, version 21.0.0, IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) statistical software. The Pearson Chi-square test and the t -test were used to determine whether there were any significant differences. The level of statistical significance was set at P < 0.05.

Fifty-one patients (24 males and 27 females) with both COVID-19 and new-onset AIS (group A) and 160 COVID-19 patients (86 male and 74 female) without new-onset AIS (group B) were surveyed. Table 1 shows the comparison of the demographics and clinical characteristics between these groups. Group A patients were significantly older (73 ± 13 years vs. 66 ± 14 years, P < 0.001) and were more likely to present with critical COVID-19 (51% vs. 30%, P = 0.004). In-hospital mortality was significantly higher in group A (52.9% vs. 18.1%, P = 0.001). Group A were more likely to have other underlying disorders, including hypertension (HTN) (74.5% vs. 55%, P = 0.013), diabetes mellitus (DM) (54.9% vs. 36.2%, P = 0.017), previous stroke (21.5% vs. 5% P ≤ 0.001), ischemic heart disease (IHD) (39.2% vs. 20% P = 0.008), and atrial fibrillation (AF) rhythm (31.4% vs. 5% P ≤ 0.001). Group A was more likely to admit to the ICU (60% vs. 26.2% <0.001). The duration of hospitalization in both ward and ICU was greater in group A (15.7 ± 15.4 vs. 7.3 ± 4.8, P ≤ 0.001 and 11.4 ± 8.9 vs. 7.1 ± 5.2, P = 0.011, respectively). Group A showed significantly lower O 2 saturation in the emergency room (82.4 ± 8.3 vs. 85.7 ± 7.8, P = 0.011). During hospitalization, pulmonary thromboendarterectomy (PTE) occurred in 6 (11.7%) patients in group A and 1 (0.6%) patient in group B ( P < 0.001).

Demographics and clinical characteristics of patients with coronavirus disease-2019 with or without new-onset acute ischemic stroke

COVID-19=Coronavirus disease 2019; ICU=Intensive care unit; AIS=Acute ischemic stroke; OR=Odds ratio; O 2 =Oxygen

Table 2 summarized the laboratory findings in two groups. Patients in group A had higher white blood cell count (10323 ± 6093 vs. 7865 ± 4447 × 109/L, P = 0.002), higher neutrophil count (8788.2 ± 5759.2 vs. 6248.7 ± 3823.9; P < 0.001), lower lymphocyte percentage (11 ± 7% vs. 15 ± 10, P = 0.007), and higher neutrophil-lymphocyte ratio (NLR) (13.9 ± 17.2 vs. 8.03 ± 8.31, P = 0.001). Lymphocyte count, erythrocyte sedimentation rate, and C-reactive protein level showed no statistically significant differences between the two groups. Moreover, D-Dimer levels (2876 ± 2479 vs. 1344 ± 1196, P < 0.001), BUN, and BUN/Cr ratio were significantly higher in group A ( P < 0.001). The analysis of venous blood gases variables in the emergency room revealed lower PH and HCO3 in group A (7.23 ± 0.42 vs. 7.30 ± 0.07, P = 0.040 and 19.33 ± 5.47 vs. 22.75 ± 7.92, P = 0.005, respectively). Serum level of albumin was significantly lower in AIS patients (3.31 ± 0.46 vs. 3.70 ± 0.45, P < 0.001).

Laboratory findings of patients with coronavirus disease-2019 with or without new-onset acute ischemic stroke

ESR=Erythrocyte sedimentation rate; CRP=C-reactive protein; WBC=White blood cell; Hgb=Hemoglobin; PLT=Platelet; Cpk=Creatine kinase; LDH=Lactate dehydrogenase; PT=Prothrombin time; PTT=Partial thromboplastin time; ALT=Alanine transaminase; AST=Aspartate transaminase; BUN=Blood urea nitrogen; Cr=Creatinine; Na=Sodium; K=Potassium; CA=Calcium; Ph=phosphor; Mg=Magnesium; BS=Blood sugar; AIS=Acute ischemic stroke; COVID-19=Coronavirus disease 2019

In agreement with previous literature, patients with AIS were older and more likely to die and have cardiovascular and cerebrovascular risk factors including HTN, DM, IHD, AF, and previous stroke.[ 4 , 5 , 7 ] The high prevalence of common vascular risk factors could be independently associated with the occurrence of stroke among patients with COVID-19 and play a significant role in the pathogenesis of this condition.

In brief, the binding of human angiotensin-converting enzyme 2 receptor and SARS-CoV-2 surface protein spike that cause endothelial apoptosis and neuronal damage mentioned as a probable association of COVID-19 severity and neurological symptoms.[ 8 ] Furthermore, hyperinflammatory state from cytokine storm followed by a prothrombotic state is frequently complicated by both venous and arterial thromboembolism.[ 9 ] Critical COVID and hypoxia in admit were more common in group A. Patients with critical illness were 2.5 fold more likely to be at risk of AIS. Bhatia et al . reported critical illness in 74% of patients with COVID and cerebrovascular disease (CVD).[ 3 ]

We showed higher leukocytosis and neutrophil count, lower lymphocyte percentage, and higher NLR in group A. Previous reports are almost the same, for example, Yao et al . compared 25 COVID-19 patients with new stroke and 2361 COVID-19 patients without stroke; they found that patients with stroke are more likely to have leukocytosis, neutrophilia, and lymphocytopenia and anemia.[ 6 ] Leukocytosis, lymphopenia, and high NLR are all inflammatory biomarkers that could be used as an indicator of systemic inflammation.[ 10 ] These blood parameters are independent predictors for the disease severity and survival of patients with COVID-19.[ 5 , 10 , 11 ]

D-dimer was significantly higher in group A. D-dimer is both a thrombus indicator and an acute phase reactant factor. D-dimer rise is basically due to a severe underlying COVID-19 infection.[ 12 ] Several studies have reported elevated levels of D-dimer in patients with COVID-19 and stroke.[ 13 , 14 , 15 , 16 ] As mentioned elevated D-dimer levels in critically ill patients with COVID-19 could be the causes of abnormal blood coagulation function in the early stage and could render patients prone to acute CVD. Accordingly, AIS patients more tended to develop PTE during hospitalization.

As shown in previous studies, the presence of multiple organ dysfunction and over-activated systematic inflammation is more common in COVID-19 patients with stroke than in those without stroke.[ 13 ] In our study, the BUN and BUN/Cr ratios were higher in group A patients. Yao et al . reported higher levels of BUN and Cr in patients with AIS.[ 6 ] Another study showed higher levels of BUN and Cr among 11 patients with COVID and CVD in comparison to those without CVD.[ 13 ] An increased BUN level is a predictive factor of extrapulmonary organ injuries. Higher initial levels of BUN together with D-dimer are associated with mortality in COVID-19 patients and are used as an assessment tool for the prediction of mortality and severity in patients with COVID-19. Furthermore, it is mentioned in previous studies that BUN/Cr ratio is an independent predictor for COVID-19 severity and can help to identify high-risk cases.[ 10 , 17 ]

Limitations

First, it would be better to include more patients. Second, we did not measure other coagulation-and inflammatory-related indices, i.e., antiphospholipid antibodies, fibrinogen, interleukin-6, factor VIII, and Von Willebrand factor.

Patients with AIS were older, had a more critical infection, more cardiovascular, and cerebrovascular risk factors (HTN, DM, IHD, AF, and previous stroke). Furthermore, we found that COVID-19 patients with higher leukocytosis, neutrophil count, NLR, D-Dimer, BUN, and BUN/Cr are more likely to develop stroke. These findings suggest that stroke in COVID-19 are probably multifactorial, and physicians should pay more attention to patients with critical infection, vascular risk factors, and those with higher mentioned laboratory markers.

Financial support and sponsorship

Conflicts of interest.

There are no conflicts of interest.

Acknowledgments

This article has been approved by the ethics committee of the Isfahan University of Medical Sciences under the registration # IR. MUI. MED. REC.1400.300.

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Woman experiences an acute ischemic stroke five weeks after tooth extraction: Case study

USA: A case report published in the Journal of the American Dental Association has highlighted the rare association between a dental procedure, infective endocarditis, and an acute ischemic stroke.Zachary M. Wilseck, University of Michigan-Michigan Medicine, Ann Arbor, MI, and colleagues revealed that the risk of developing stroke and infective endocarditis is low among low-risk patients, but...

USA: A case report published in the Journal of the American Dental Association has highlighted the rare association between a dental procedure, infective endocarditis, and an acute ischemic stroke.

Zachary M. Wilseck, University of Michigan-Michigan Medicine, Ann Arbor, MI, and colleagues revealed that the risk of developing stroke and infective endocarditis is low among low-risk patients, but it is not nonexistent.

In the case described, the patient was initially deemed to be at low risk and, therefore, not given prophylactic antibiotics before tooth extraction, and, therefore, the development of infective endocarditis led to the detection of valvular abnormalities.

"Proper identification, prompt management, and close interdisciplinary collaborations are important to improve outcomes in these patients," the researchers wrote.

The case concerns a 54-year-old woman who experienced an acute ischemic stroke five weeks following a tooth extraction. The initial symptoms of this patient included right facial drop and mild to moderate word-finding difficulty. Computed tomographic angiography showed a left M1 segment middle cerebral artery occlusion (thrombolysis in cerebral infarction scale, 0) with reconstitution of the distal middle cerebral branches through arterial collaterals.

Following the initial administration of tissue plasminogen activator, endovascular thrombectomy was performed successfully with thrombolysis in cerebral infarction scale 3 (complete) recanalization.

After the procedure, there was an improvement in the patient's language and neurologic deficits. Imaging showed bilateral, multifocal, cortical, and deep brain hemorrhages. Blood cultures grew Streptococcus mitis, ultimately leading to endocarditis diagnosis. Echocardiographic imaging revealed moderate to severe aortic insufficiency, mitral valve vegetation, and mild mitral valve regurgitation.

The cardiothoracic surgery team evaluated the patient after which she was discharged with intravenous antibiotics and short-term outpatient follow-up with the cardiothoracic surgery team.

The case highlights an association between a dental procedure, infective endocarditis, and acute ischemic strokes resulting from large-vessel occlusion or embolus.

In conclusion, dental procedures are generally safe, however, can introduce oral bacteria into the bloodstream, resulting in bacterial seeding of cardiac valves and subsequent infective endocarditis.

The researchers suggest the importance of recognizing infective endocarditis after a dental procedure, including tooth extraction, as a potential cause of an acute ischemic stroke so that prompt treatment can be initiated.

"Dental procedures can be a potential source of bacteremia, leading to the development of infective endocarditis and subsequent complications such as hemorrhagic or ischemic stroke," the researchers wrote.

"Vigilance is important in recognizing the signs and symptoms of infective endocarditis, specifically in patients who have undergone dental interventions and have underlying cardiac conditions or are immunocompromised, they concluded.

Bah, M. G., Wilseck, Z. M., Lin, L. Y., Peterson, A. J., Chaudhary, N., & Gemmete, J. J. (2024). The interplay among a dental procedure, infective endocarditis, and an acute ischemic stroke. The Journal of the American Dental Association, 155(3), 244-250. https://doi.org/10.1016/j.adaj.2023.11.009

MSc. Biotechnology

Medha Baranwal joined Medical Dialogues as an Editor in 2018 for Speciality Medical Dialogues. She covers several medical specialties including Cardiac Sciences, Dentistry, Diabetes and Endo, Diagnostics, ENT, Gastroenterology, Neurosciences, and Radiology. She has completed her Bachelors in Biomedical Sciences from DU and then pursued Masters in Biotechnology from Amity University. She has a working experience of 5 years in the field of medical research writing, scientific writing, content writing, and content management. She can be contacted at  [email protected]. Contact no. 011-43720751

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: [email protected]. Contact no. 011-43720751