A 51 year old man presented to the Emergency Department (ED) with acute onset left sided peripheral facial palsy and a complete right sided homonymous hemianopsia.\nThe patient was a Caucasian male of normal BMI with no prior history of hypertension, hypercholesterolemia, diabetes, smoking and or heart disease. He had been in good health until March 2020 when he returned from a group holiday to Austria. The patient started feeling unwell with a fever and was diagnosed with coronavirus disease (COVID-19) along with several members of the group that he had travelled with. A nasopharyngeal PCR swab confirmed the presence of SARS-CoV-2 RNA on the 22nd of March 2020. The patient was admitted the hospital on the 29th of March 2020 after increasing shortness of breath and onset of diarrhea and vomiting. The patient was febrile but had no oxygen requirement and was therefore diagnosed with mild COVID-19. He was admitted for observation, managed conservatively, and was discharged home 3 days later on the 1st of April 2020 after showing clinical improvement.\nThe patient was readmitted 2 days later on the 3rd of April 2020 with increasing shortness of breath. Clinically, pulmonary embolism (PE) was suspected with no signs of hemodynamic compromise. The diagnosis was confirmed by a CT Pulmonary Angiography (CTPA) (Fig. ) which demonstrated multiple bilateral subsegmental PE with no signs of right sided heart strain. The CTPA also demonstrated bilateral ground glass and consolidation in the lungs in keeping with COVID-19 infection (Fig. ). The CT examination was performed using the Siemens® Somatom Definition Flash using GE Healthcare® Omnipaque intravenous contrast and a standardized CTPA protocol. The patient had a D-dimer > 4.0 mg/L (normal range 0.2–0.6 mg/L). The Chest CT performed during the CTPA also shows the radiological extent of the COVID-19 illness in the lungs (Fig. ). The patient was started on Low Molecular Weight Heparin (LMWH) with bridging to direct oral anticoagulation (DOAC) on a dose of 20 mg Rivaroxaban OD. The patient continued DOAC treatment for a total of three months until the beginning of July 2020.\nOn the 26th of February 2021, approximately 11 months after being diagnosed with COVID-19, the patient contacted the emergency medical services due to acute onset visual field disturbances. The ambulance arrived on scene minutes after the onset of symptoms. A preliminary examination by the paramedics revealed as right sided visual field defect and a left sided facial palsy. The patient had a heart rate of 70 beats per minute and blood pressure of 147/89 mm Hg. The prehospital oxygen saturation was 98 % whilst breathing room air. Based on their initial findings, the paramedics suspected a stroke, and the patient was blue lighted to the ED.\nOn admission to the ED the patient was taken directly to the CT lab. The patient had a temperature of 35.5 ℃, ECG showing normal sinus rhythm, blood glucose of 5.8 mmol/L, a blood pressure of 157/99 mmHg and an oxygen saturation of 99 % on room air. A rapid neurological examination revealed a left sided peripheral facial palsy, right sided homonymous upper quadrantopia. A National Institutes of Health Stroke Scale (NIHSS) exam revealed a score of 3.\nA CT scan was performed including a pre- and intra- cerebral angiography. A subsequent cerebral perfusion scan was also performed. The CT examination was performed using the Siemens® Somatom Definition Flash using GE Healthcare® Omnipaque intravenous contrast and standardized protocols for angiography and perfusion.\nThe plain CT showed no signs of hemorrhage and based on the clinical suspicion of stroke the decision to treat with intravenous thrombolysis was made. Alteplase was administered at a dose of 0.9 mg/kg as per guidelines. The CT angiography three occluded intracerebral vessels, occlusions of the P2 and P3 segments of the left posterior cerebral artery (Fig. ) and an occlusion of the left superior cerebellar artery. The CT perfusion scan show increased time to drain (TTD) and reduced cerebral blood flow (CBF) in the afore mentioned occluded vascular territories (Fig. ).\nThe patient was admitted to the stroke unit and showed neurological improvement after Alteplase administration. The following day the patient had a NIHSS of 0.\nDuring hospital admission examinations were performed to determine ischemic stroke etiology. Ultrasound of the pre- and intra- cerebral vessels showed no significant stenoses or occlusions. Five day in-hospital cardiac rhythm monitoring showed sinus rhythm without any signs of atrial fibrillation and or other arrythmia. The patient underwent a Trans- Thoracic Echocardiography (TTE) which was normal and a Trans- Esophageal Echocardiography (TEE) where a patent foramen ovale was detected (PFO). The right to left shunting was visualized on color doppler and whilst using contrast (Fig. ). A blood work up during admission showed a normal ESR, normal levels of Immunoglobulin G and M, normal levels of Protein C and S and normal Factor Xa activity. Immunological assays did not detect the presence of rheumatoid factor, ANCA, ANA, anti-CCP antibodies. Furthermore, no factor V Leiden mutation was detected nor the presence of Lupus anticoagulant. The only abnormal finding was an elevated D-dimer of 1.2 mg/L (normal range 0.2–0.6 mg/L). A full body CT was performed including a CTPA and a CT venography of the lower extremities. The full body CT showed no signs of malignancy. The CTPA showed no evidence of pulmonary embolus and the CT venography of the lower extremities ruled out deep vein thrombosis (DVT).\nThe patient was discharged with a NIHSS of 0 following an Embolic Stroke of Unknown Source (ESUS). The patient is currently being treated with 20 mg Rivaroxaban OD, and atranscatheter closure of his PFO has been scheduled.
A 62-year old male patient was referred to our center with subacute onset of a cerebellar syndrome manifesting in writing disability and severe gait instability. Sixteen days earlier, he had developed acute-onset cough and high fever for 7 days, and 4 days after onset of upper airway symptoms, he experienced acute ageusia and anosmia for eleven days. Medical history was unremarkable. Clinical, imaging and laboratory findings are summarized in Table .\nThe patient presented with a cerebellar syndrome with slightly scanning speech and limb-, truncal- and gait ataxia at admission, i.e. 16 days after onset of COVID-19 respiratory illness and 1 day after resolution of symptoms of COVID-19 affecting the upper respiratory tract. Examination of the eye movements including vertical and horizontal saccades, saccadic pursuit and vestibulo-ocular reflex, was normal. No pathological nystagmus was observed. No opsoclonus or myoclonus was observed. Sensory functions including vibration sense, joint position sense, light touch, pin prick and temperature sensation, were normal; muscle tone, shape, strength and deep tendon reflexes were also normal. His vital signs on admission were normal. Lung auscultation was regular, but CT of the chest showed bipulmonary opacities. He tested positive for SARS-CoV-2 RNA via reverse-transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swab using the Roche Cobas SARS-CoV-2 test (Roche, Basel, Switzerland) on day 2, but tested negative again on day 6 of hospital admission. Cerebral MRI imaging (Fig. a-d) showed a mild cerebellar atrophy of unclear etiology, in particular, the patient did not have a history or signs of pre-existing cerebellar disease such as alcohol abuse or gluten hypersensitivity. We ruled out paraneoplasia by whole-body FDG-PET and screening for anti-neuronal antibodies including anti-CASPR2, −LGI1, −Glut, −GlyR, −Hu, −Ri, −Yo, −Amphiphysin, −CV2 (CRMP5), −Ta/Ma2, −Ma1, −SOX1, −GAD65, −ZIC4, −Tr antibodies in cerebrospinal fluid (CSF) and serum, and anti-MOG antibodies in serum. FDG-PET was performed 13 days after onset of cerebellar symptoms and showed normal cerebellar and cerebral metabolism (Fig. e). Laboratory results showed no increase in inflammatory markers in peripheral blood, in particular CRP and white blood cell count were normal. CSF testing including cell count, protein, CSF/serum albumin ratio and Reibergram was normal. Isoelectric focusing revealed identical oligoclonal bands in CSF and serum (type 4, see Table ), indicating systemic inflammation of various etiology but no intrathecal IgG production. Notably, SARS-CoV-2 RT-PCR [] from CSF was negative. In addition, no viral nucleic acid was detected in metagenomic virus sequencing [] from CSF. An in-house developed, bead-based antibody assay (ABCORA, Luminex technology) for detection of IgG antibodies against subunit 1 (S1) and subunit 2 (S2) of the spike protein and nucleoprotein (NP) of SARS-CoV-2 was used to screen for SARS-CoV-2-specific antibodies in serum and CSF. We calculated CSF/serum-antibody index according to Reiber [], and CSF/serum-antibody index > 1.5 indicated intrathecal antigen-specific antibody production. SARS-CoV-2-specific antibodies were positive in serum, but there was no intrathecal SARS-CoV-2-specific antibody production. PCR testing of CSF for DNA of herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), JC polyomavirus (JCV) and varicella zoster virus (VZV) were also negative. No intrathecal antibody production reactive to HSV-1, HSV-2, VZV or Borrelia burgdorferi was detectable.\nEmpirical treatment with systemic acyclovir 3x10mg/kg body weight/day was given over 6 days, as herpes viral cerebellitis could not be excluded until day 33. The possibility of cerebellar infection with SARS-CoV-2 was discarded because of the normal CSF cell count and the absence of SARS-CoV-2 RNA and intrathecal SARS-CoV-2-specific antibody production. Other causes such as infections with other viruses, other autoimmune and/or paraneoplastic diseases or intoxication were excluded by details of the past medical history, results of the CSF analysis, auto-antibody screening and FDG-PET. In order to treat a possible post-infectious etiology, namely a post-infectious cerebellar ataxia, we additionally started high-dose methylprednisolone 500 mg/day i.v. over 5 days without subsequent tapering. The cerebellar syndrome improved slowly and slightly over a course of 20 days before acyclovir and corticosteroid treatment, and improved more rapidly with the steroid treatment, which was initiated 14 days after resolution of COVID-19-related respiratory symptoms, i.e. 13 days after onset of ataxia and 7 days after negative SARS-CoV-2 nasopharyngeal swab. The Scale for the Assessment and Rating of Ataxia (SARA ataxia score) improved from SARA 14 points on admission (onset of ataxia, i.e. day 16 after onset of COVID-19) to SARA 5 points 6 days after beginning of steroid treatment (i.e. day 35 after onset of COVID-19), and SARA 1 point nearly 4 months after beginning of steroid treatment (i.e. day 119 after onset of COVID-19). Steroid treatment was well tolerated without re-occurrence of COVID-19 symptoms.