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Cerebral venous thrombosis (CVT) is a form of cerebrovascular disorders that is difficult to recognize, it is potentially a life threatening condition and requires timely anticoagulant therapy. In the era of the COVID-19 pandemic, there is a steady increase in CVT (4.2% vs. 0.5-1%). At the same time, mortality in patients with CVT on the background of COVID-19 significantly exceeds the mortality in patients with CVT without COVID-19 (45.5% vs. 15%). Objective(s): to study the clinical course of CVT, to determine the diagnostic value of radiological methods and the significance of genetic risk factors for thrombosis in the development of CVT in young and middle-aged patients against the background of COVID-19. Material and methods. Seven patients were examined: six women (five of them of reproductive age) and one man, aged 26 to 57 years (mean age 37 years). The main clinical and neurological manifestations of CVT, the results of laboratory examination, neuroimaging, and the data of molecular genetic analysis of risk factors for thrombosis were analyzed. Results. The course of COVID-19 was severe in one case, and moderate in the rest of cases. The interval between the onset of COVID-19 symptoms and the development of CVT ranged from 7 to 25 days. In three cases CVT had an acute course and was accompanied by the development of a stroke (in two cases, hemorrhagic stroke was noted, in one case, multifocal ischemic stroke), in other cases, a subacute course of CVT was noted. Genetic risk factors for thrombosis were identified in all patients. Conclusion. The diagnosis of CVT in the era of the COVID-19 pandemic is particularly difficult, since the most common symptom of CVT - headache (90%) - can be regarded as a manifestation of COVID-19. At the same time, timely diagnosis of CVT and immediate initiation of anticoagulant therapy are associated with a relatively favorable prognosis.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Introduction: Cerebral venous sinus thrombosis (CVST) is a rare but potentially debilitating thrombosis affecting 3-4 cases per million adults in the United States. Risk factors are thought similar to venous thrombosis, but there is little epidemiologic data corroborating this assertion. Concern about a possible association between the Janssen (Johnson and Johnson) and Oxford-AztraZenaca COVID-19 vaccines and cases of CVST resulted in increased global attention to this condition. Thus, large epidemiological assessment of the risk factors, treatment and outcomes of CVST are needed. Objective(s): Estimate the distributions of risk factors antecedent to CVST diagnosis, report CVST treatments in clinical practice, and potential sequelae of CVST in a large retrospective cohort of adults with CVST in the United States. Method(s): MarketScan Commercial and Medicare Supplemental administrative databases were employed to assess CVST diagnosed between 2011 and 2019 in the U.S. Validated International Classification of Disease (ICD) codes and receipt of an outpatient anticoagulant (either oral or subcutaneous anticoagulant) prescription within 30 days of the ICD code identified incident CVST. Antecedent clinical characteristics, treatments, and sequelae of CVST were identified using inpatient, outpatient, and prescription data. For outcomes, proportions and incidence with 95% confidence intervals (CIs) were calculated, stratified by sex. Result(s): We identified 1,869 CVST patients. Of these 1,314 (70%) were female, with 200 (10%) events identified as a pregnancy-related CVST. The average age was 41 years for females and 48 years for men. Among women, 24.7% were on hormonal therapy (oral contraceptive, estrogen, and progestin) prior to diagnosis. Men had a higher prevalence of comorbidities, such as diabetes (15% men vs. 9% women) and cancer (19% men vs. 10% women). Oral anticoagulant (OAC) use was the most common treatment for CVST in both men (88%) and women (85%) and did not vary by sex. Use of procedures to treat CVST, optic nerve fenestration and catheter directed thrombolysis, were 0.5% and 4.1%, respectively. The most common sequela after CVST was incidence of intracranial hypertension (Incidence: 4.2 per 100 person-years;95% CI: 3.3, 5.1) and palliedema was rare. Conclusion(s): Overall, a majority of CVST patients were women of reproductive age. Our findings suggest a potential association with both endogenous (pregnancy) and exogenous (oral contraceptives, HRT) hormones which needs further study. In our sample, CVST was managed with oral anticoagulants, regardless of sex, and intracranial hypertension was elevated following CVST. This large claims-based analysis is a descriptive insight into the risk factors and management of CVST, a rare and debilitating condition.
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OBJECTIVES: The aim of the survey was to find out what the possible consequences are of the COVID-19 disease on the nervous system and to propose a method of using artificial intelligence. MATERIAL AND METHODS: Recent research has shown that the risks to patients due to severe acute coronavirus 2 respiratory syndrome (SARS-COV-2) differ most significantly depending on age and the presence of underlying comorbidities such as: cardiovascular disease, hypertension, diabetes and others. The consequences of COVID-19 on the nervous system are especially important. We performed a detailed selection of articles describing the effects of COVID-19 on the nervous system. RESULT(S): We made a clear summary of the main consequences of COVID-19 on the nervous system and suggested a way to use artificial intelligence. CONCLUSION(S): We confirmed research that artificial intelligence methods have the potential to accelerate prediction, especially for the possible consequences of COVID-19 on the nervous system.Copyright © 2020 Neuroendocrinology Letters
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The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.
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Introduction In early 2021, unanticipated thromboses, including cerebral venous sinus thrombosis (CVST) with thrombocytopenia, emerged as an adverse reaction (ADR) in patients who had been vaccinated with the AstraZeneca ChAdOx1 nCoV-19 vaccine. This ADR was termed vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). Although sporadic in nature, VITT can result in severe disease in the individual vaccinee. We followed up on the outcomes and status of neurological recovery of 49 cases of VITT with CVST that were reported to PEI. Method Assessment of the Extended Glasgow Outcome Scale (GOS-E) was performed within 3-6 months after the initial hospital admissions. Individual Glasgow Coma Scale (GCS) scores were reported by phone or electronically via a questionnaire or medical report by the treating physician of the hospital to which the patient was initially admitted. If a GCS score was not reported, an expert determined a score based on the patient's medical report. For most patients, follow-up was pursued about 3-6 months after hospital admission. The reported outcomes describe the patients' neurological status at 5-38 weeks (mean 20 weeks) after hospital admission. Outcomes were identified in 44 of the original 49 cases. Results Patient outcomes ranged from good recovery (13 patients, 29.6 %) to moderate disability (11 patients, 25.0 %) and severe disability or vegetative state (6 patients, 13.6 %). Fatal outcomes were reported in 14 patients (31.8 %). As anticipated, initial low GCS scores were associated with poor outcomes. By contrast, GCS scores > 10 were typically associated with improved neurological outcomes. Moreover, platelet count nadirs were correlated with patient outcomes. Low platelet counts were observed in fatal cases (GOS-E 1) with a mean count of 17,000 platelets/muL). Likewise, patients with better neurological outcomes (GOS-E scores of 5-6 and 7-8) presented with mean counts of 61,000 thrombocytes/muL. However, the course of the disease was not always predictable and showed significant individual variability. Conclusion We provide data on the outcome of VITT cases with CVST upon vaccination with the AstraZeneca adenoviral vector ChAdOx1 nCoV-19 COVID- 19 vaccine and found that the recovery of patients from CVST was very heterogeneous. While some patients exhibited good recoveries, others developed severe disabilities and major long-term complications. Collectively, our findings highlight the importance of paying attention to early signs of increased intracranial pressure and the onset of thrombocytopenia in patients with a recent history of vaccination with the AstraZeneca adenoviral vector ChAdOx1 nCoV-19 COVID-19 vaccine.
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Background Vaccines are considered one of the milestones of modern medicine that promoted health and curbed morbidity and mortality. However, with the rapid development and approval of various vaccines, various thrombotic events have been reported. Yet, a comprehensive analysis of vaccine and stroke and other thrombotic events is not well-characterized. Methods To investigate the relationship between vaccines and thrombotic disorders, we utilized vaccine adverse event reporting system (VAERS) database between 1990-2021 using key medical terms. The data was stratified based on sex and age, and type of vaccine. The COVID-19 vaccine was additionally stratified based on manufacturer. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with 95% confidence interval (CI). Results More than 1,300,000 adverse events reported between 1990-2021 in FAERS database. Over 6000 cases of stroke have been reported between 1990-2021. As expected, most of the reported stroke (70%) occurred in older patients (>50 years old). Interestingly, the incidence of vaccine-associated stroke is slightly more in females (52%) compared to males (44%). Among all the vaccine-related stoke, COVID-19 vaccines were associated with over 80% of all stroke reported with ROR (CI 95%) of 13.3 (CI 12.4-14.3, p<0.0001). Subclassification analysis of COVID-19 vaccines revealed that Pfizer/Biontech COVID-19 vaccine was associated with 46%, Moderna (40%), and Janssen (12%) of all COVID-19 associated stroke. Finally, our data revealed that prothrombic diseases of various vascular beds were reported the most among patients who have received COVID-19 vaccines. Among these thrombotic events, deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis were the most predominant. Conclusion Thrombotic events related to vaccines are rare but still feared due to their high morbidity and mortality. In this study, ischemic stroke was most reported among the COVID-19, Zoster, and Influenza trivalent injected vaccine. This retrospective study highlights the urgent need for further longitudinal studies to examine the safety of vaccines in patient with high risk for thrombosis.Copyright © 2023 American College of Cardiology Foundation
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Introduction: Cerebral venous sinus thrombosIs (CVST) is a rare condition compared to other categories encountered in stroke medicine.It occurs more frequently in patients with conditions that predispose them to other venous thrombosis, such as thrombophilias, acute malignancies, nephrotic syndrome, and COVID-19. CVST was identified as one of the rare causative of stroke. The exact mechanism of the stroke is not fully understood. However, a commonly agreed pathophysiology is that a dysfunction in arachnoid granulation can lead to sinus occlusion. Subsequently, this leads to a reduction in cerebral fluid drainage, which can increase intracranial pressure, causing capillary hypertension, cerebral oedema, decrease in cerebral perfusion pressure and venous haemorrhage. The European Stroke Organisation (ESO) supports using both MRI/MR Venogram and CT venogram as modalities for diagnosis of CVST, with no particular preference of one over the other. The standard practice in the management of cerebral venous sinus thrombosis includes treating the clot and its precipitating factors and treating the sequela of the clot as in the case we are reporting. Yet, there is no clinical guideline for the more aggressive measures to break down the clot in either AHA or European Stroke Organization, but they are used in clinical practice, with promising results in certain cases. Our case is an example of a successful mechanical thrombectomy with a lifesaving outcome. Method(s): We are reporting an unusual case of a 27- year- old lady who presented to the hyperacute stroke unit with dense right- sided weakness and expressive dysphasia. After an initial CT (Computerised Tomography) scan confirming extensive cerebral venous sinus thrombosis, she went for urgent mechanical thrombectomy. The clinical assessment after the procedure showed significant recovery in power of the right limbs and speech. She was discharged 7 days later with near full recovery. Venous thrombectomy is a rarely performed procedure. However, in this case, it was potentially lifesaving and resulted in an excellent clinical outcome. Result(s): An MRI/MRV follow up in a month demonstrated that the lesion on left centrum semiovale had regressed compared to the first scan. Also, there was some evidence of recanalization of her transverse sinuses. She was assessed by the therapist two months from the event. The patient reported some word finding difficulties and clumsiness in the right hand and leg. However, no further major event since her thrombectomy, and now aiming to get back to work. Conclusion(s): Mechanical thrombectomy in cerebral venous sinus thrombosis can be an effective, life-saving, and safe procedure with an extremely rewarding outcome. It should be considered in patients with acute neurological deterioration despite anticoagulant therapy.
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Introduction: COVID-19, a new coronavirus illness, swiftly spread throughout all continents. However, evidence on all of COVID-19's indications and symptoms is lacking. Patients who have COVID-19 may be more susceptible to fungal infections. Mucormycosis is an uncommon and frequently fatal fungal illness caused by hyphae invading the bloodstream and causing thrombosis and necrosis. Material(s) and Method(s): Patients diagnosed with mucormycosis following a recent COVID-19 infection were included in the case series analysis. Surgical therapy was limited to individuals who tested negative for COVID-19 on PCR. To remove the infection, endoscopic, open, and combination techniques were used. For the first month after surgery, survivors were followed up on on a regular basis. Result(s): About 30 people with a history of Covid-19 were given dexamethasone and remdesivir in this study. Following therapy, these individuals developed mucormycosis, which was treated by Functional Endoscopic Sinus Surgery (FESS). As a consequence, 16 patients (53.34 %) had numerous operations. The most prevalent related condition was diabetes mellitus (60 %). The majority of the patients were men (60 %). Our patients had an average age of 55.53+/-8.093. 43.34 % of the people died. Conclusion(s): In conclusion, mucormycosis is a rare but critical problem complicating the later part of the clinical course of COVID-1, possibly due to improper drug usage during Covid treatment. Copyright © 2023 Authors. All rights reserved.
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Background: Among young people, cerebral venous thrombosis (CVT) is a major cause of stroke and females are more likely to develop cerebral venous thrombosis. Objective(s): Thus, the present study aimed to study the clinical profile of CSVT in adults and compare them between both genders and specific age groups. Methodology: The clinical characteristics of 40 male and female patients with and without CVT who had been admitted to the Chettinad Hospital & Research Institute, India, from Feb 2020 to Sep 2021 were included. Result(s): Out of 40 patients, 77.5% were female, and 22.5% were male. The most commonly involved cranial nerve was 7th, contributing 15%, while the involvement of cranial nerves 3rd and 6th contributed 5% and 12.5%, respectively. However, 67.5% of patients had no cranial nerve involved. Covid was diagnosed in 4 patients (10%), and the remaining 36 patients (90%) were diagnosed negative for covid. Cerebrovascular accident (CVA) present in 17 patients. Further, we noticed that 7 patients had left sided stroke and 9 were with right sided stroke. The cranial nerve involved was iii, vi, and vii in 1,3 and 6 patients with CVA, while the cranial nerve involved was iii and vi in 1 and 2 patients without CVA respectively. Further, out of 40 patients, Covid was diagnosed in 2 patients with CVA and 2 without CVA. We have observed a statistically significant difference in focal defects only in with and without CVA patients. Conclusion(s): Males were more likely to develop CVT than females, according to a prior international study. A significant risk factor was alcoholism. The gender gap, clinical profile, and risk variables are not significantly different from earlier Indian investigations. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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The coronavirus disease (COVID-19) with its rapid spread and high mortality rate has caused major disruptions. It involves the nervous system. COVID-19 also causes infection in the brain stem which may influence chemosensory neural cells related with respiratory and cardiovascular regulation and also neurons of the respiratory center. This study evaluates the effects of COVID-19 on neurological complications and cognitive. Several studies were reviewed for the effects of COVID-19 on neurological complications and cognitive function. COVID-19 causes signs such as headache, altered mental status, anosmia, myalgia, ischemic stroke, developed cerebral hemorrhage, and cerebral venous sinus thrombosis, olfactory disorders, anosmia, losing taste, mental retardation, migraine, Guillain-Barre syndrome, encephalopathy, severe abduction deficits in both eyes, esotropia, epilepsy, hypogeusia, hyposmia, faulted consciousness and seizures. It also caused cognitive function such as Alzheimer's disease, cognitive worsening, depression, anxiety, tiredness, anxiety, decrease in BDNF, stress and fatigue. In conclusion, COVID-19 causes negative effects on neurological system and cognitive function which must be considered for the treatment of the disease in alongside clinical treatments. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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INTRODUCTION: Multisystem Inflammatory Syndrome in Adults (MIS-A) is an underrecognized post-infectious manifestation of COVID-19.We report a case of a 21-year-old male with MIS-A who presented with adrenal hemorrhages, acute kidney injury (AKI) and cerebral strokes leading to multiorgan system failure and death. DESCRIPTION: A 21-year-old, morbidly obese male presented at an outside hospital with COVID-19 and abdominal pain. His abdominal CT demonstrated bilateral adrenal hemorrhages, he was discharged home on hydrocortisone. A month later was readmitted with fever, diarrhea, thrombocytopenia and AKI. Laboratory work revealed creatinine 5.49mg/dL, ferritin 701ng/ml, BNP 3020 pg/ml and D-Dimer 17,650 ng/ml. He received hydrocortisone, intravenous immunoglobulin and enoxaparin. Fever subsided and renal function normalized. On day 7 he developed acute altered mental status and recurrent AKI. Head CTA showed multiple short stenotic segments in the anterior circulation, diminutive appearance of several intracranial arteries and basal ganglia hypodensities. Brain MRA demonstrated extensive bilateral acute/subacute strokes, no evidence of sinus thrombosis and markedly decreased caliber of internal carotid, left middle and anterior cerebral arteries without evidence of thrombus. He received aggressive neurocritical care management including decompressive craniectomy and pulse steroids for suspected vasculitis. Due to the severity of his neurological injury and poor neurologic prognosis family elected to withdraw support. His autopsy demonstrated hepatomegaly, acute tubular necrosis, bilateral adrenal hemorrhages and hypercellular bone marrow with myeloid predominance. Neuropathology showed severe segmental stenosis of the carotid arteries and bilateral vertebral arteries. DISCUSSION: Stroke is a potentially life-threatening complication of COVID-19 including large vessel occlusion and less frequently vasculitis-like phenotype with vessel wall enhancement. Despite initial improvement, our patient developed an acute extensive ischemic stroke leading to a devastating neurologic injury. The neuropathology findings suggest SARS-CoV-2 associated vasculitis. Stroke in the context of COVID-19 may have different pathogenetic mechanisms, clinical characteristics and complications that warrant further investigation.
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In this study we investigated a link between adenovirus-based vaccines, deployed to fight the SARS-CoV-2 pandemic, and lifethreatening thromboembolisms after vaccination. Post-marketing surveillance showed that, following vaccination, Vaxzevria (ChAdOx1 based, AstraZeneca) and Jcovden (Adenovirus type 26 based, Johnson & Johnson) are associated with reduced platelet counts (thrombocytopenia) and blood clots (thrombosis) in some individuals. This extremely rare condition, with a rate between 1:50,000 - 1:350,000 cases per vaccinated individual, is above background rates of thrombosis in the population and can lead to fatal ischemic events including cerebral venous thrombosis, intracranial haemorrhage, and pulmonary embolism. It has been termed vaccine induced thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). Heparin induced thrombocytopenia (HIT) is another condition with a similar clinical presentation to TTS. In HIT, immunoaggregates are formed due to the presence of strong anti-selfantibodies directed against Platelet Factor 4 (PF4). When similar anti-PF4 antibodies were detected in TTS patients, we investigated whether there could be a link between the adenovirus vectors used in the vaccines and PF4. This study demonstrates a direct interaction between adenovirus capsids and PF4 using surface plasmon resonance. We then utilized an integrative structural biology workflow including cryo-electron microscopy and molecular dynamics to characterize and demonstrate the mechanism of this interaction. These results demonstrate a previously unknown adenovirushost interaction and provide critical clues as to the underlying mechanism which causes TTS, including how these pathogenic anti-PF4 antibodies may be induced. We are therefore able to present a hypothesis as to the route of pathogenesis in TTS.
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In this review, we summarise the current knowledge on vaccine-induced immune thrombotic thrombocytopenia (VITT) and new insights into its underlying pathogenesis. VITT is characterised by severe thromboses occurring 5-20 days after vaccination with an adenoviral vector-based SARS-CoV-2 vaccine (AstraZeneca or Johnson & Johnson). Thromboses typically involve the cerebral sinus and venous system. Routine laboratory analyses show thrombocytopenia and high D-dimer levels. The pathogenesis is based on immunological processes similar to those in heparin-induced thrombocytopenia. Accordingly, VITT is associated with high-titre immunoglobulin G directed against platelet factor 4 (PF4). Interaction with adenoviral vector-based vaccines leads to modifications of PF4 allowing antibody-producing cells to identify PF4. Anti-PF4 antibodies activate platelets through FcgammaIIa receptors. The detection of platelet-activating anti-PF4 antibodies confirms the diagnosis of VITT. Treatment is based on anticoagulation, which inhibits thrombin itself or thrombin formation, and high-dose intravenous immunoglobulin G, which inhibits cell activation via FcgammaIIa receptors. In severe cases, plasma exchange could also be an option. In some patients, a pre-VITT syndrome precedes VITT. Pre-VITT patients typically present with severe headache before thromboses are manifest. The early identification of a pre-VITT syndrome allows for the prevention of thrombotic complications. The specific dynamics of the immune reaction in VITT correspond to a transient, secondary immune response. Current studies address how PF4 binds to different adenoviral proteins and investigate the functional role of other vaccine components. Some of these factors contribute to the induction of a pro-inflammatory danger signal that triggers the first stage of VITT pathogenesis. In the second stage, high-titre anti-PF4 antibodies activate platelets and granulocytes. In a process called NETosis (neutrophil extracellular traps), activated granulocytes release DNA. Anti-PF4 antibodies then bind to complexes of PF4 and DNA. This enhances further cell activation via Fcgamma receptors and consequently also the formation of thrombin. At the end of the article, we comment on how the current knowledge on VITT may influence global vaccination campaigns against SARS-CoV-2 and we address how anti-PF4 antibodies may be involved in recurrent arterial and venous thromboses not associated with VITT and HIT. Copyright © 2022 Georg Thieme Verlag. All rights reserved.
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An atypical case of VITT was described resulting from a vaccination schedule where the third booster with ChAdOx1 nCoV-19 (AstraZeneca) was administered. The patient received a complete vaccination schedule with two doses of Pfizer-BioNTech (BNT162b2) without any complications before the third dose. However, the patient has developed an infrequent yet extreme prothrombotic;hypercoagulable state caused by platelet-activating anti-Platelet Factor 4 (PF4) antibodies. This phenomenon is typically triggered by the proximate administration of an adenoviral vector vaccine against COVID-19. The patient's symptoms began ten days after taking the third dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). His main complaints when hospitalized were severe headaches and right abdominal pain. The blood tests and MRI scan imaging findings were very characteristic of VITT, and a rare cerebral venous sinus thrombosis was found. Also, a markedly elevated D-dimer and strong positive PF4-dependent enzyme-immunoassay test results were documented. Due to discerning clinical suspicion, this patient was rapidly treated with immunoglobulin infusion for two days and oral steroids for three days. Subsequently, he was anticoagulated with the new oral anticoagulant edoxaban after platelet numbers recovery. In a few days, platelets normalized, and D-dimer levels decreased, while anti- PF4-dependent enzyme-immunoassay test results showed a slow decline. He was discharged taking oral edoxaban without any sequeal. Copyright © 2022
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Introduction: Neonatal diabetes mellitus (NDM) a rare cause of hyperglycemia in the neonatal phase, occurring in 1/300,000 case is characterized by a genetic mutation causing hyperglycemia in the first 6 months of age. We will present the case of a 5-week-old male with NDM, presented with hyperventilation, dehydration and complicated by status epilepticus and venous sinus thrombosis to review the pathophysiology, the complications and management options. Case Description: A 5-week-old male born at term appropriate for gestational age, presented for dehydration and lethargy. Urine analysis to rule out urinary tract infection showed glycosuria and ketonuria unmasking severe hyperglycemia of 1400 mg/dL. Sepsis workup was negative. There is no history of consanguinity nor family history of diabetes, but we note COVID infection 4 weeks ago. Intravenous insulin and hydration were started, then our patient complicated by respiratory distress, metabolic acidosis and status epilepticus. Three days later, clinical improvement was seen. An ultrasound of the head and abdomen were normal, and brain MRI showed a venous sinus thrombosis treated with anticoagulation. A1C was 5%, insulin level 1 mUi/mL, C peptide 1.36 ng/mL. Genetic analysis showed no mutation in the parents, but a de novo heterozygous mutation of the ABCC8 gene in our patient. Our patient was switched to subcutaneous insulin, and a decrease in the insulin need was seen over 3 months without the need of sulfonylureas. And the final diagnosis of our patient was transient NDM with the need of regular follow-ups to detect any relapse in the future. Discussion(s): NDM is characterized by a severe hyperglycemia in the first 6 months of age. The most frequent genetic causes of NDM with abnormal pancreatic function are aberrations in the 6q24 locus and mutations of the ABCC8 or KCNJ11 genes. We will focus on the ABCC8 gene coding for the ATP-potassium channel, which has an essential function in the cascade of insulin secretion. When glucose is low this channel is hyperpolarized, and when glucose increases, this channel is depolarized. This depolarization activates the calcium channels, enabling the release of insulin. Activating mutations will cause hyperpolarization of this channel, blocking the cascade of insulin release. NDM is stratified based on its progression as transient or permanent NDM. Transient NDM resolves within months and may relapse years later. The chief complaint can be dehydration and difficulty to thrive. The presence of a polyuria with frequent heavy wet diapers, in the setting of dehydration should raise the suspicion of NDM. Many complications can be seen like cerebral edema, and hypercoagulable state. Our patient developed a venous sinus thrombosis prevalent in 0.67 case/100000 cases/year. The initial treatment would be insulin injections, and in the presence of endogenous insulin production, estimated by C peptide levels, starting sulfonylureas is an option. The high relapse frequency suggests the need of regular follow-up during childhood and adolescence. Copyright © 2022
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Background: Cerebral venous thrombosis (CVT) is a major cause of stroke in young adults. Is more frequent in women, it may appear related to pregnancy or the use of hormonal contraceptives. Its symptoms are nonspecific, often with a normal neurological examination. Its diagnosis is based on imaging tests and in most cases, if treatment is started early, the prognosis may be favorable. Aim(s): Describe the characteristics of CVT in patients that we have had in our clinic. Method(s): We compiled data from patients with CVT followed up in our hemostasis consultation in the last 6 years. Patient data were collected through hospital medical records. Result(s): We have a series of 15 cases, most of them women (73.3%). The average age of the series is 38.6 years (range from newborn to 64 years). The most frequent symptoms were epileptic seizures in 40% and headache in 33.3%. In 45.5% of women, CVT was related to pregnancy or the puerperium, and in 27.3% of the women it was associated with taking oral contraceptives. Thrombophilia (genetic or acquired) has been found to be involved in 33.3% of cases. The remaining cases were associated with breast cancer (1), trauma (1), severe anemia (1), and SARS-CoV vaccines (1). In two cases (13.3%) decompressive neurosurgery was required. In two cases (13,3%), direct oral anticoagulant (apixaban and dabigatran) were used. In 60% of cases anticonvulsant treatment was associated. In 40% of cases, the evolution was very favorable without sequelae, recurrent headache was found in 53,3% of cases. Conclusion(s): CVT is a rare but important cause of stroke in young adults. CVT it is not easy to diagnose, partly due to its relative rarity, its multiple and various clinical manifestations and interpret correct brain imaging. We must keep it in mind to avoid delay in diagnosis and treatment. (Table Presented).
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Background: With widespread COVID-19 immunization efforts, reports of vaccine-induced thrombocytopenia and thrombosis (VITT) have emerged, particularly in association with adenoviral vector-based vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S). The incidence of VITT is considered to be extremely low, with the benefits of vaccination strongly outweighing associated risks. Despite the favorable safety profile of COVID-19 vaccines, VITT has garnered the attention of and likely contributes to vaccine hesitancy among a persistently unvaccinated portion of the United States population. Aim(s): We sought to characterize thrombotic events following COVID-19 vaccination in a large clinical enterprise where mRNA-based vaccines were mostly administered. Method(s): With institutional approval, medical records of 779,602 patients vaccinated against COVID-19 (2 mRNA-based vaccines: 61.2% BNT162b2, 36% mRNA-1273, and adenovirus-based Ad26. COV2.S, 2.7%) from 12/4/2020-6/ 6/2021 at Cleveland Clinic Enterprise locations in Ohio and Florida were queried. A baseline complete blood count was available for 223,345 patients, of which 663 (0.3%) demonstrated thrombocytopenia-defined as >=50% platelet decline 4-28 days post-vaccination- and were subject to chart review. Thrombotic events including deep vein thrombosis, pulmonary embolism, stroke/transient ischemic attack, myocardial infarction, cerebral venous sinus thrombosis, and splanchnic thrombosis were assessed. Thrombotic risk factors including medications, viruses, and malignancy, as well as platelet factor 4 antibody assays were recorded. Result(s): Of 76 patients with thrombosis, 63 (82.9%) demonstrated clear etiologies. Thirty (39.5%) had malignancies (24 treated with chemotherapy associated with thrombosis risk). Seven (9.2%) were considered hypercoagulable, six (7.9%) had catheter-related thrombosis, five (6.6%) had recent surgery, five (6.6%) had reduced mobility, five (6.6%) had cardiovascular risk factors, three (3.9%) had diagnosed/suspected immune thrombocytopenia, and two (2.6%) were septic. Of three patients with unprovoked thrombosis, one had findings concerning for VITT (Figure 1). Conclusion(s): 76/223,345 (0.03%) patients demonstrated thrombosis following COVID-19 vaccination, with one (0.0004%) case concerning for VITT. In a large clinical enterprise, VITT is exquisitely rare.
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Background: Vaccine induced thrombotic thrombocytopenia (VITT) is a rare but severe complication following vaccination with ChAdOx1 nCoV-19. Antibodies directed against platelet factor 4 (PF4) are thought to be responsible for platelet activation and subsequent thromboembolic events in these patients. Because of the similarities between heparin-induced thrombocytopenia (HIT) and VITT heparin was avoided but the risk of thrombosis in VITT upon heparin administration remains unclear. Aim(s): To assess the impact of heparin used as initial anticoagulants to treat VITT. Method(s): We prospectively analyzed follow up data from 4 patients with confirmed VITT patients (3 women and 1 men;median age, 44 years [range, 22-62 years]). ELISA and functional VITT testing was performed at each time point. Result(s): The patients' clinical symptoms started between days 4 and 17 after first vaccination with ChAdOx1 nCoV-19. All patients presented with thrombocytopenia and thromboembolic events (amaurosis fugax and peripheral thrombosis and venous sinus thrombosis). The follow-up duration ranged between 8 weeks and 9 months. No additional thromboembolic event or disease progression occured in any patient. A recovery in platelet count was monitored in all four patients within 10 days after starting treatment (heparin or alternative anticoagulation combined with IVIG). In both patients who were treated with heparin, anti-PF4 antibodies were not detectable after 3 and 19 weeks respectively. All 4 patients received mRNA-based vaccine as second vaccination against SARS CoV2. No significant drop in platelet count or new thromboembolic complication was observed. Conclusion(s): In the treatment of VITT, early beginning of anticoagulation with close follow-up of the platelet count and thrombosis signs seem to be more important than the choice of anticoagulant. Subsequent vaccination with an mRNA vaccine appears to be safe in VITT patients.
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Case Diagnosis: A 37-year-old woman with daily headaches after Johnson & Johnson (J&J) COVID-19 vaccine. Case Description or Program Description: A patient with 10 months of daily headaches notes an inability to care for her son and complete daily tasks. Headaches started immediately after receiving the J&J COVID-19 vaccination. Headaches are burning, aching, throbbing, and begin occipitally "creeping" bilaterally over the scalp. The patient has no past medical history including headaches or migraines. Over 10 months, she has seen multiple specialties. Initial differential included atypical migraine, immune reaction post-vaccine with possible underlying Lyme disease activation, and atypical shingles. Therapy, chiropractic services, and multiple pharmacological treatments offered no relief. Imaging of the brain and neck was normal. Setting(s): Physical Medicine and Rehabilitation (PM&R) clinic. Assessment/Results: Upon evaluation in PM&R, palpation of bilateral greater occipital nerves reproduced symptoms. Based on this chronic bilateral occipital neuralgia was diagnosed. Bilateral greater occipital nerve blocks were offered for diagnostic confirmation and therapeutic relief. To ensure relaxation of the neck musculature therapeutic exercises were provided. Discussion (relevance): Neurological side effects after J&J COVID-19 vaccine are reported including Guillain-Barre syndrome, Bell's Palsy, and cerebral venous sinus thrombosis. 1 Additionally, mild neurological events such as headache, anxiety-related syncope, and dizziness are frequently reported after vaccination. Each of these cases is characterized as acute, and symptoms tend to resolve within a month.1 To our knowledge, this is the first reported case of chronic bilateral occipital neuralgia developing following a standard dose of the J&J COVID-19 vaccine. Conclusion(s): These findings suggest chronic bilateral occipital neuralgia is a potential side effect of the J&J COVID-19 vaccine. It is necessary to consider bilateral occipital neuralgia on the differential for headache following vaccination, as chronic pain can impair a patient's ability to perform activities of daily living.
ABSTRACT
Objective: To describe a case of Anterior Spinal Artery (ASA) syndrome after vaccination -coincidence or causality? Background: As efforts to improve SARS-CoV-2 vaccination continue, more questions safety of the vaccination continues to be raised. Ischemic stroke, intracerebral hemorrhage, and cerebrovascular venous sinus thrombosis have been reported in the literature after COVID -19 mRNA vaccination. Although rare cases of acute transverse myelitis have also been reported, literature regarding post-COVID vaccination ASA syndrome is even rarer. Design/Methods: A 32-year-old female with no significant past medical history presented with acute onset of bilateral extremity weakness and numbness that started 2 weeks ago. Result(s): Patient was awake, alert, and oriented. Physical examination showed decreased tone in wrist bilaterally. Motor examination was normal except for 1/5 handgrip, 2/5 wrist, and 3/5 triceps bilaterally. Triceps and brachioradialis reflexes were absent bilaterally. Sensory examination showed absent pinprick sensations C7 and below. Vibration and proprioception sensations were intact. Patient was recently admitted at outside hospital for same complaint. Neurological work was unremarkable except of an enlarged 4th ventricle for which she underwent left frontal ventriculostomy. Lumbar puncture showed normal IgG index and negative serum NMO Ab. She was treated with IVIG for presumed inflammatory disorder with minimal improvement. Patient underwent a repeat neurological workup at our facility due to ongoing symptoms. EKG showed normal sinus rhythm CT head showed prominent 4th ventricle. CT spine were unremarkable. MRI of the brain showed Postprocedural changes associated with recent prior left trans frontal ventriculostomy catheter. MRI of the cervical and thoracic spine showed T2 hyperintense lesion extending from C3/4 to T1 with central predominance rostrally, whole cord involvement at C5, and with anterior predominance caudally with extent to the upper thoracic level of T1;shows patchy enhancement. TTE was unremarkable. Infectious and hypercoagulable workup was also unremarkable. Patient-reported receiving first dose of Moderna mRNA Covid vaccine 2 weeks prior to onset of symptoms. She was discharged to rehab on aspirin and atorvastatin. Conclusion(s): Our patient presented with symptoms and imaging consistent with ASA syndrome 2/2 infarct of an anterior spinal artery C5-T1. Extensive neurological, infectious, rheumatological, and hypercoagulable workup was negative for etiology. The patient had onset of symptoms after receiving her first dose of mRNA COVID-19 vaccine, however, unclear if the presentation is consistent with postvaccination vaccine ASA syndrome or idiopathic.