A 72-y-old nonsmoking man with a single episode of transient global amnesia 10 y previously presented with progressive diffuse arthralgia and a sore throat (day 0). Two days afterward, his general practitioner started josamycin for 4 d. On day 8, the patient exhibited an episode of fever (38°C–38.5°C) without rhinorrhea, cough, or dyspnea, leading to the prescription of azithromycin. He never experienced anosmia or ageusia. On day 12, chest CT showed peripheral bilateral ground-glass lesions and consolidative opacities suggestive of SARS-CoV-2 infection. The symptoms improved gradually. On day 17, he started to develop bilateral upper-limb action tremor. The next day, the tremor worsened, involving the lower limbs and trunk, making walking and sitting impossible and leading to his admission to the hospital.\nNeurologic examination showed a cerebellar syndrome (action tremor, ataxia, dysarthria, and upper-limb dysmetria) associated with spontaneous diffuse myoclonus, mostly affecting the proximal limbs and worsening with movement, also stimulus-sensitive. The remainder of the neurologic examination showed normal findings, including ocular motility and deep tendon reflexes. His body temperature, oxygen saturation, respiratory rate, and lung auscultation were normal. A moderate biologic inflammatory syndrome was present, with increased fibrinogen (7.07 g/L; reference level, 1.90–4.30 g/L) and C-reactive protein (14 mg/L; reference level, 0.0–5.0 mg/L).\nThe first nasopharyngeal swab test for SARS-CoV-2 was positive (day 18), as was the serology afterward (strongly positive for IgM and IgG). The next swab tests, quantitative reverse-transcription polymerase chain reaction testing of nasopharyngeal or oropharyngeal swabs, were negative (days 21, 22, 26, and 27).\nElectroencephalography showed symmetric diffuse background slowing, reactive to stimulation, without interictal paroxysm and, notably, no correlation of the myoclonus on back-averaging. Brain MRI with gadolinium contrast injection had normal results (). Brain PET with 18F-FDG showed putaminal and cerebellum hypermetabolism associated with diffuse cortical hypometabolism, confirmed by whole-brain voxel-based SPM quantification (). Slight lung and hilar lymph node hypermetabolism was noticed, matching postinfectious pseudonodular retractile consolidation on CT, without a straightforward argument for neoplasia.\nCerebrospinal fluid (CSF) testing showed normal cell counts (4 × 106/L), a mildly elevated protein level (49 mg/dL), negative reverse-transcription polymerase chain reaction, and no oligoclonal banding. Nerve tissue immunostaining with the serum and CSF revealed the presence of autoantibodies directed against the nuclei of Purkinje cells, striatal neurons, and hippocampal neurons, as illustrated with the CSF in . This immunostaining did not evoke any previously described targets for autoimmune encephalitis. The titer of the IgG isotype autoantibodies in the serum was extremely high (1/25,000) but was 1/96 in the CSF. The same intensity and reactivity in serum and CSF were observed at the same IgG concentration, ruling out intrathecal autoantibody synthesis in concordance with the absence of CSF-specific IgG oligoclonal banding. Dot blot assays against onconeural antigens and cell-based assays against membrane antigens had negative results. Finally, the patient was negative for antinuclear, antiphospholipid, and antipolynuclear autoantibodies and other tissue autoantibodies.\nBecause of the suspected autoimmune nature of the encephalitis, we promptly started immunomodulatory treatment: at first, beginning on day 23, we used intravenous immunoglobulins (0.4 g/kg/d for 5 d); tolerance was good, but there was no significant clinical improvement. We then decided to treat the patient with intravenous methylprednisolone (1 g/d for 5 d) beginning on day 30. To help reduce myoclonus, we introduced oral drops of clonazepam (0.3 mg 3 times a day), but the treatment was stopped because of drowsiness. Clinically, the patient improved considerably after the methylprednisolone treatment, leading to cessation of myoclonus and upper-limb dysmetria and allowing him to walk without assistance. He was discharged from the hospital on day 37. We did not observe any signs of SARS-CoV-2 reactivation.
A previously healthy 52-year-old man presented with progressive imbalance and generalized jerks (see Supplementary video-). A week before, he had experienced myalgia and tested positive for SARS-CoV-2. Upon admission, he had generalized stimulus-sensitive myoclonus affecting his face, hands, and legs, confining him to a wheelchair. Other neurological findings, including eye movements, muscle tone, and deep tendon reflexes, were normal. He did not have any coughing, fever, dyspnea, and O2 saturation was more than 97% without nasal O2. Ground-glass opacities suggestive of SARS-CoV-2 infection were detected on chest CT. Laboratory studies showed no increase in inflammatory markers in peripheral blood; CRP and white blood cell count were normal. Brain CT and MRI were normal. Results from CSF evaluations, including autoantibody investigations, were unremarkable. The cerebellar syndrome improved after high-dose IV methylprednisolone (1 gr/day for five days); on a follow-up session after three weeks, the patient could walk independently.