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.
A previously healthy 42-year-old man presented with difficulty speaking, cognitive deficits, ataxia, and progressive disabling jerks in upper and lower limbs, leading to falls (see Supplementary video-). Neurological examination demonstrated spontaneous, action-induced, and tactile-sensitive myoclonus on the face, upper extremities, and lower extremities. He had dysmetria and dysdiadochokinesia with superimposed action-induced myoclonus in the upper and lower extremities. Myoclonus prevented him from standing independently, and he had a wide-based gait. The rest of the neurological examination was normal. Laboratory tests including renal function, liver function, ammonium, urea, and CO2 were normal, except for the nasopharyngeal RT-PCR test for SARS-CoV-2, which was positive. Computed tomography (CT) of the head and brain magnetic resonance imaging (MRI) were normal. Electroencephalogram (EEG) and electromyography (EMG) were performed but did not reveal any abnormalities. Given these findings and the positive SARS-CoV-2 PCR, myoclonus was considered postinfectious. No other symptoms such as fever, myalgia, cough, fatigue, hyposmia, or hypogeusia were present. Cerebrospinal fluid (CSF) analysis was unremarkable, RT-PCR test for SARS-CoV-2 and autoantibodies were negative. He was treated with methylprednisolone 1000 mg IV daily for five days, bringing about a partial resolution of myoclonus. Complete recovery was observed on a follow-up session one month later.