key: cord-0971085-y428l6yk authors: Ahmed, Manzoor; Gaba, Waqar Haider; Al Mazrouei, Safaa Saeed title: Neuro-Imaging Manifestations of COVID-19: Predilection for PICA Infarcts date: 2021-04-20 journal: IDCases DOI: 10.1016/j.idcr.2021.e01131 sha: abddc73ac4e91987bc07c4838d9170693ce4f34d doc_id: 971085 cord_uid: y428l6yk COVID-19 has been an ever-evolving viral pandemic which can cause systemic disturbance especially in some of the critically ill patients. Neurologic or Neuro-imaging manifestations of COVID-19 are being increasingly reported in these patients and mainly consist of ischemic strokes, hypoxic ischemic injury and non-specific encephalopathy. Ischemic strokes as expected more commonly afflict major vascular territories, likely due to accentuated hypercoagulability in these patients. Certain vascular territories may be more susceptible to ischemic infarcts. We observed higher predilection for infarcts in posterior inferior cerebellar artery (PICA). This may represent another peculiarity of this pandemic. hypercoagulability in these patients. Certain vascular territories may be more susceptible to ischemic infarcts. We observed higher predilection for infarcts in posterior inferior cerebellar artery (PICA). This may represent another peculiarity of this pandemic. Introduction: COVID-19 pandemic has been caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is strong association with coagulopathy causing arterial and venous thrombosis [1] [2] [3] [4] . The triggering of coagulopathy is linked to alveolar damage resulting in an inflammatory storm. There is activated production of inflammatory cytokines including IL-6 with multi-fold sequential effects particularly generation of pro-coagulative factors and damage to endothelium, which in turn sets up the field for thrombosis and arterial to arterial J o u r n a l P r e -p r o o f thrombo-embolism [5, 6] . Hence, there is an association of COVID-19 with ischemic stroke, however the pathogenesis is likely multi-factorial rather than merely COVID-related coagulopathy [7] as there is a high incidence of cardiovascular disease or associated comorbidities (like diabetes and hypertension) in patients with severe COVID-19 [7] and the infection itself has shown to be a risk for stroke even before COVID-19 [8] . The reported cases of ischemic strokes in COVID-19 patients mainly affected medium to large vessels territorial infarcts [9, 10] in comparison to more common small vessel ischemic disease in patients with high risk for cerebrovascular disease. Khan et al [11] recently reported 22 cases of acute ischemic stroke in COVID-19 patients, 18 of them presented with strokes. Majority involved major vascular territories-about 65% anterior circulation, 27% posterior & 15% mixed. However, the overall incidence of stroke in COVID-19 patients has been low-about 5% from one of the study from China [12] . Belani showed COVID-19 as an independent risk factor for stroke [13] . Avula et al [10] had majority of their cases involving posterior circulation. We also present here 6 out of 9 stroke cases affecting posterior circulation, all these patients turned out to be COVID-19 positive on PCR testing. All these patients had sub-acute infarcts of posterior inferior cerebellar artery (PICA) on imaging. This case series attempts to highlight the predilection for PICA infarcts in COVID-19 cases as well as sub-acute clinical presentation and eventual manifestation during their hospitalized course due to COVID-19. This adds to many peculiarities of COVID-19 as being revealed while we battle this pandemic. Ischemic stroke is one of the many neurologic or neuro-imaging manifestations of COVID-19 [14] . During the first wave of pandemic in four months, we had 983 patients admitted in our institution, proven positive for COVID-19 on PCR or serologic testing and 9 had evidence of acute or sub-infarcts on neuroimaging. Six cases with PICA infarcts were further studied. All cases had initial non-contrast CT head while all except one case had follow up MRI stroke exams to confirm the PICA infarcts. As part of institutional protocol for COVID-19 testing, almost all patients had available biochemical lab profile as part of standard protocol in our J o u r n a l P r e -p r o o f institution. The demographic, clinical and biochemical profile is presented in Table 1 . The neuroimaging features of each case are elaborated as below with corresponding figures: We present a case series of COVID-19 patients with mostly isolated PICA infarcts. Predilection for PICA distribution may be another revealing unique manifestation of COVID-19, a disease which certainly needs more exploration specially its Neurologic Manifestations. COVID-19 as a systemic infectious disorder raise the risk for stroke in these patients with potential to cause altered clinico-imaging presentation, distribution and course of infarcts as somewhat evident from our study. Our cases were focused on cerebellar infarcts in COVID-19 patients. Large size cerebellar infarcts represent vascular territorial infarcts in PICA, AICA and SCA distribution. The dominant cause of PICA infarcts is also arterial-arterial thrombo-embolism from extracranial large arteries followed by cardio-embolism or in-situ disease [15] . However, hyper-coagulability can certainly contribute to cerebellar infarcts. This can be the potential mechanism in strokes related to COVID-19. In two of our patients, infarcts were large enough to involve more than half of PICA distribution. PICA is a peculiar vessel due to its tortuous course and high variability in its course [16] . About 10% of cases have extra-dural origin of PICA [16] . The patterns of PICA infarcts can also be grossly divided into distribution of medial and lateral branches. Kumral et al [15] studied cerebellar infarcts and showed about 30% infarcts in medial branch distribution, 10% lateral branch, 10% both medial and lateral branches, 25% involving superficial or deep water-shed of cerebellar arteries, and 10% had PICA infarcts along with infarcts in other vertebra-basilar distribution. Though cerebellar infarcts constituted only 2% of all the infarcts, but about half of the cases had isolated PICA infarcts suggesting its higher predisposition to infarcts and may be further accentuated by COVID-19. All our cases had posterior-inferior and or medial distribution without brainstem involvement. The infarcts were demarcated on CT due to sub-acute onset. The sub-acute features of infarcts were also manifested on MRI as mixed restriction diffusion, cortical laminar necrosis, hemorrhagic change and or enhancement. Posterior circulation infarcts are prone to present clinically late as sub-acute infarcts usually due to J o u r n a l P r e -p r o o f non-specific symptoms [17] . Some of the infarcts also had associated cerebellar vasogenic edema and surface hyperintensity on FLAIR images mimicking cerebellitis ( Figure.4) , inflammatory process can be a plausible differential diagnosis in the setting of COVID-19 and may even be contributing to relative atypical appearance of the infarct. Beyrouti et al [9] described a link between ischemic stroke and COVID-19 infection in the context of a highly prothrombotic state. We observed similar phenomenon in our cases where all patients had positive D-dimers and 3 out of 6 had values >20mcg/mL while 4 out of 6 patients had ischemic stroke despite being on prophylactic or full dose anti-coagulation. Incidentally, all these four patients had late presentation of stroke during the course of COVID-19 disease. Cases with presentation or detection of cerebral or cerebellar infarcts during hospital course can be plausibly attributed to systemic effects of COVID-19. However, patients primarily presenting with ischemic strokes certainly raise the possibility of coincidence with COVID-19 given its pandemic status in the community. The peculiarity of these cases, especially manifestation, on neuroimaging does lend an attributive if not causative role to COVID-19. As noted above, about 80% of the cases presented as ischemic strokes in one of the recently reported study [11] . Author Statement: I Waqar Haider Gaba, corresponding author agree with the changes suggested by the reviewers. I have made changes in main text accordingly and answered all queries. I authorise the changes made to our article. 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