Hyperhomocysteinemia is related to large vessel occlusion in young patients with COVID-19, two case reports
Seyedehnarges Tabatabaeea , MD, Fatemeh Rezaniab , MD, Sevim Soleimanic , Zahra Mirzaasgaria *, MD
a Division of Neurology, Firoozgar hospital, Iran University of Medical Sciences, Tehran, Iran
b Neurosciences Department, St Vincent’s hospital, Melbourne, Victoria, Australia
c School of Medicine, Shahid Beheshti Medical University, Tehran, Iran
Corresponding author: Zahra Mirzaasgari, MD, Division of Neurology, Firoozgar hospital, Iran University of Medical Sciences, Tehran, Iran
E-mail: Mirzaasgari@gmail.com
Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.
Abstract:
Here, we report two cases of previously healthy young men with COVID-19 infection who developed acute ischemic stroke due to large vessel occlusion followed by secondary events concerning for a further thromboembolic event. We hypothesize that the hypercoagulable state related to COVID-19 exacerbated the underlying hereditary thrombophilia.
Background:
Numerous neurological complications of COVID-19 have been identified. Severe infection with corona virus could result in headache, epilepsy, myasthenia gravis, cerebrovascular events and encephalitis (1-5). Coagulopathy is a common feature of the disease and it is associated with poor prognosis (6). The association between hyperhomocysteinemia and cerebrovascular disorders have been studied (7). Elevated plasma homocysteine levels could take place secondary to insufficient intake of vitamin B12, vitamin B6, and folic acid as well as a genetic predisposition. Mutations in the gene encoding the protein MTHFR are the most commonly known genetic risk factor for hyperhomocysteinemia. The most common MTHFR mutations are two single nucleotide polymorphisms (SNP), C677T and A1298C. Both SNPs result in a decreased MTHFR activity, which may cause hyperhomocysteinemia (8-9). Here we present two young Asian men with a potential –previously silent- hereditary thrombophilia who presented with COVID-19 pneumonia and two consecutive thromboembolic events; i.e. ischemic stroke and NAION.
First case: A previously healthy 39-year-old Asian man was admitted to hospital with 10 days prodromal symptoms of fever, chills, malaise and cough (Table 1). There was a positive family history for recurrent deep vein thrombosis in his mother and maternal aunt. The oropharyngeal swab test for coronavirus disease 2019 (COVID-19) by qualitative RT-PCR was positive. He was commenced on COVID-19 treatment with Remdicivir as well as prophylactic anticoagulation. Despite this his respiratory symptoms were not improving. Ten days into his admission, he developed a left hemiparesis involving the face and limbs. He underwent emergent clot retrieval with recombinant tissue plasminogen activator (rTPA). His brain CT-scan showed hypodensity within right middle cerebral artery (MCA) territory (Fig 1.a). He was commenced on dual antiplatelets with Aspirin 100 mg daily and Clopidogrel 75 mg daily and atorvastatin 80 mg daily. He was intubated shortly after this due to altered conscious state together with severe respiratory involvement. Upon completion of another 7 days of treatment for COVID19 pneumonia with Remdicivir and Dexamethasone he was successfully extubated. Unfortunately, he declined further evaluation and left the hospital against medical advice at this point. He then represented few days later with a painless right eye vision loss upon waking in the morning. This presentation was about one month after his initial respiratory symptoms. He was transferred to our center to undergo diagnostic work-ups. He underwent carotid Doppler ultrasonography that showed right ICA complete occlusion. This was confirmed by DSA that showed a complete occlusion of proximal right carotid artery (fig 1.b). His trans-thoracic echocardiography revealed a large aortic arch thrombus (fig 1.c). He was commenced on anti-thrombotic regime, initially with Heparin infusion. This was switched to Rivaroxaban 20mg daily after. Dual antiplatelet therapy was ceased. A complete ophthalmic examination was performed by ophthalmologist who found a relative afferent pupillary defect (RAPD), a normal optic disc and impaired color vision (as examined by Ishihara color test) in the right eye. His visual acuity was reduced to hand motion in the right eye. Intraocular pressure, extraocular movements, and slit-lamp examination were normal. His ophthalmic history was unremarkable. The occurrence of consecutive thromboembolic events in the absence of other risk factors except for COVID infection urged us to run an extensive thrombophilia screen. Homocysteine level was found to be elevated at 50µmol/L (normal lab reference less than 15). Vitamin B12 and folic acid level were normal. MTHFR activity examined by genetic testing reveled a homozygous MTHFR A1298C variant. He continued on stroke preventive therapy with Rivaroxaban 20mg daily and atorvastatin 80mg daily, patient was discharged and lost to follow up.