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 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.