A 26-year-old female patient with a past medical history of obesity, post-traumatic stress disorder, depression, and exercise-induced asthma presented to the emergency department with sudden onset of headache, vomiting, and right-sided numbness, and tingling. The patient underwent computed tomography (CT) angiography of the head and neck, which were unremarkable, and no vertebral artery dissection was seen. She was discharged with the diagnosis of migraine.\nShe developed worsening of her symptoms at home, presenting again to the emergency department with increasing right-sided numbness, weakness, and dysarthria. Vital signs were stable with no fever. The patient reported no respiratory symptoms and denied any recent head trauma or chiropractic neck manipulation. The neurological exam was significant for right-sided weakness, dysarthria, right-sided dysmetria, and gait ataxia. Chest X-ray showed no acute infiltrates. Magnetic resonance imaging (MRI) of the brain showed an acute right cerebellar infarct with the involvement of the right cerebellar peduncle (Figure ). Magnetic resonance angiography of the head revealed narrowing of the right superior cerebellar artery (Figure ). An echocardiogram with a bubble study was performed, as well as a part of a stroke workup, which showed a PFO. The lower extremity venous doppler ultrasound was negative for deep venous thrombosis. The laboratory test results are shown in Table .\nThe patient was screened for COVID-19 with a nasopharyngeal reverse transcription polymerase chain reaction due to increased reports of stroke in young patients nationwide, and the test came back as positive, to our surprise. Standard stroke treatments, including aspirin, clopidogrel, and high-intensity statins, were initiated for the patient. Enoxaparin for deep venous thrombosis prophylaxis was also prescribed.
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.