A 68-year-old man presented in June 2020 to the emergency room with a fall due to progressive lower extremity weakness and numbness, occurring shortly after the peak of the initial coronavirus surge in New York City. The patient had a history of benign prostatic hyperplasia and hyperlipidemia. He reported that beginning one month prior to presentation he developed diminished sensation in his feet. Over the course of several weeks the numbness progressively ascended to the level of the lower abdomen and included the perianal region. Subsequently, he developed low back pain, urinary retention, and constipation. He reported experiencing several falls due to his weakness and sensory loss, which culminated in a mechanical fall whereby he sustained a left distal fibular fracture, prompting medical attention. He denied any visual changes, headaches, dizziness, shortness of breath, fatigue, arthralgias, myalgias, fevers, loss of smell or taste, or any recent upper respiratory or gastrointestinal illness; he never had symptoms suggestive of COVID-19 disease and was never previously tested for it. He denied recent travel with his last trip being to Europe and Israel in the 1980s.
Upon admission, the patient underwent casting of the fibular fracture and a foley catheter was placed for his urinary retention. His physical examination was notable for abdominal distension with moderate tenderness and stool burden in the left lower quadrant. Neurologic examination showed he was fully oriented with fluent, clear speech and normal cranial nerve exam. He had normal bulk, tone, and confrontation strength in both upper extremities. There was right lower extremity diminished tone, and assessment of the left lower extremity was limited due to the casting. There was Medical Research Council (MRC) grade 2/5 hip flexion strength bilaterally, 4+/5 knee extension bilaterally, 2/5 knee flexion bilaterally, and 4/5 ankle dorsiflexion and plantar flexion on the right. Deep tendon reflexes were notable for 3+ right patellar responses, bilateral crossed adductors, absent right Achilles reflex, and upgoing plantar responses on the right. Multimodal sensation testing was normal in the upper extremities, however, there was dense sensory loss to all modalities including proprioception below the approximate T8 spinal level. Given a reproducible spinal sensory level, initial considerations focused on a myelopathic process.
Work up in the emergency department included MRIs of the cervical, thoracic, and lumbar spine which showed areas of cervical and thoracic spondylosis and mild cervical and lumbar canal narrowing without cord signal changes. These chronic findings were felt unlikely to explain the patient’s acute symptoms. He was admitted to the neurology service for further evaluation and management. The patient underwent extensive additional neuraxial imaging including repeat contrast MRIs of the spine that showed a potential subtle hyperintense signal in the dorsal cord at T10 (Fig 1A). Given the persistent concern for a myelopathic process, a spinal MR angiogram and two conventional spinal angiograms were performed which failed to demonstrate vascular abnormalities of the spinal cord and dura. An MRI brain incidentally showed non-specific faint bilateral, symmetric T2/FLAIR hyperintensities in the brainstem surrounding the fourth ventricle. These findings were felt likely metabolic in etiology, although Wallerian degeneration of the upper motor neuron was also considered.
The serum laboratory workup was notable for elevated SARS-CoV-2 IgG antibody (12) (titer of 1:2880), elevated C-reactive protein (31.6 mg/L) and erythrocyte sedimentation rate (22 mm/hr). Nasopharyngeal swab for SARS-CoV-2 PCR was negative. Serum angiotensin converting enzyme, complement C3/C4, creatinine kinase, TSH, Vitamin B12, Vitamin E, copper, zinc, thiamine, fatty acids, RPR, EBV PCR, and enterovirus RNA PCR were not detected or within normal limits. Other antibody studies including anti-MOG and NMO IgG, anti-SSA/SSB, ANA, ANCA, anti-DNA, anti-Hu, rheumatoid factor, anti-mycoplasma, Lyme IgG/IgM, hepatitis A/B IgG/IgM, ant-hepatitis C, HIV IgG/IgM, HTLV I/II, Polio types 1 and 3, VZV IgG, West Nile Virus IgG/IgM, autoimmune encephalopathy and motor sensory neuropathy/ganglioside panels were negative.
Lumbar puncture was performed three weeks after his fall. CSF profile revealed 10 red blood cells/µL, 0 white blood cells/µL, glucose 62 mg/dL, and protein at 38 mg/dL. An incidental positive West Nile Virus IgG antibody was detected, but CSF was negative for West Nile Virus IgM antibodies and PCR. Additional infectious and inflammatory workup was also negative for bacterial, fungal, and viral cultures, Biofire PCR panel, enterovirus PCRs, oligoclonal bands, and autoimmune encephalopathy antibody panel. SARS-CoV-2 viral PCR and antibodies were also not detected in the CSF.
The patient underwent serial nerve conduction studies (NCS) and electromyography (EMG). The initial NCS were performed three weeks following his mechanical fall. This study revealed normal distal motor and sensory conductions in the upper and right lower extremities without evidence for conduction block or slowing; however, the tibial and peroneal F-wave responses and the tibial H-reflex responses were absent in the right lower extremity. EMG revealed incomplete muscle activation, but normal recruitment pattern and motor unit morphology. Repeat electrodiagnostic studies two weeks later again showed normal distal motor and sensory conductions. The repeat EMG revealed the interval development of spontaneous activity in the right vastus lateralis, iliacus, and paraspinal muscles. A single volitional motor unit of normal amplitude and duration was seen rapidly firing within the iliacus muscle, and other muscles were limited by activation.
The initial EMG results suggested a neurogenic process affecting the proximal nerve roots and or distal conus with a superimposed upper motor neuron problem causing an incomplete activation pattern (13). An active neurogenic process affecting the L3-L4 myotomes was confirmed on the second EMG by the presence of spontaneous activity as well as markedly reduced motor unit recruitment. This new data taken together with the patient’s clinical picture, and markedly elevated SARS-CoV-2 antibodies, raised the suspicion for a post-COViD-19 immune-mediated myeloradiculitis, or Elsberg syndrome.
To target a presumed neuroinflammatory autoimmune response, the patient was started on intravenous methylprednisolone (IVMP) 1,000 mg daily for 5-days. In the days following the steroid course, the patient reported some subjective improvement in both weakness and numbness. There was concurrent clinical re-emergence of the right Achilles tendon reflex. Consistent with this finding, focused NCS at that time revealed electrodiagnostic re-emergence of the peroneal and tibial F-wave (Fig 1B) and H-reflex late responses in the patient’s right lower extremity. Following completion of course of IVMP, the patient received a course of intravenous immunoglobulin (IVIg; 0.4 mg/kg/day for 5-days). His hospitalization was complicated by obstipation causing bowel edema requiring disimpaction and aggressive laxative management. He was subsequently discharged to acute inpatient rehab. At the time of follow-up three-months after symptom onset he continued to demonstrate marked paraparesis, sensory dysfunction, and bowel/bladder function, not significantly changed beyond the improvement achieved following steroid treatment.