A 31-year-old Spanish-speaking male with no significant past medical history presented to the emergency department (ED) with progressively worsening weakness, numbness, and difficulty walking. Approximately two months prior to presentation, he woke up and noticed some numbness in his right hand. One month later he noticed double vision. He started wearing an eye patch over one eye to help with symptoms of diplopia. He then started experiencing numbness in his right leg as well as left facial weakness with dysarthria. About a week later, his symptoms progressed to numbness on the left upper and lower extremity, which prompted a visit to an outside hospital. His workup was reportedly normal including a magnetic resonance imaging (MRI) of the brain and lumbar puncture. His weakness and bilateral paresthesias progressed to the point that he was unable to ambulate, which prompted his current visit. The patient denied any trauma, headache, neck stiffness, loss of vision, fever, cough, or any other infectious symptoms. He denied any recent travel, sick contacts, or contacts with similar complaints.\nOn presentation to the ED his vital signs were within normal limits, and with the exception of a malar facial rash and abnormal neurologic exam, his physical exam was unremarkable. On neurologic exam, he was awake, alert, and oriented appropriately. On primary gaze there was left-eye adduction and cranial nerve VI palsy bilaterally with extraocular movements and vertical nystagmus. He had a unilateral, lower motor neuron cranial nerve VII palsy with left upper and lower hemifacial weakness, and also cranial nerve XII dysfunction with tongue deviation to the left. Overall his motor bulk was normal and strength was 5/5 in flexor and extensor groups of all four extremities. His sensation was intact to light touch and pinprick in all extremities. He had significant dysmetria with finger-nose-finger and heel-to-shin bilaterally, slightly worse on the left with decreased amplitude and discoordination on finger tapping and other rapidly alternating movements bilaterally. All upper extremity reflexes were intact; however, he had no patellar or Achilles reflexes; he had downgoing plantar reflex on the left. and mute plantar reflex on the right. He was unable to stand or test gait secondary to significant ataxia.\nThe patient was admitted and underwent an extensive workup including infectious, autoimmune, paraneoplastic, metabolic, and neurologic testing. MRI of his brain and lumbar spine were unremarkable. A computed tomography of his chest looking for neoplasm revealed a consolidation in his left lower lobe that prompted SARS-CoV-2 polymerase chain reaction testing and returned positive. Cerebrospinal fluid (CSF) studies revealed the presence of anti-ganglioside – GQ1b (Anti-GQ1b) immunoglobulin G antibodies (1:100), with lymphocytic predominance without albuminocytologic dissociation, and he subsequently was found to have positive immunoglobulin G (IgG) antibodies to COVID–19.\nThe patient was treated with convalescent plasma, tocilizumab, and intravenous immunoglobulin, in addition to extensive physical and occupational therapy. He had some mild subjective improvement in vision and coordination as well as return of patellar reflexes bilaterally; however, he required maximum assistance to ambulate on transfer to rehab facility.
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.