Isolated bulbar palsy after SARS-CoV-2 infection

We read with interest the Article by Matschke and colleagues,¹ who detected inflammatory infiltration, predominantly in the brainstem, and proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lower cranial nerves of patients who died from COVID-19. Clinical correlates of these neuropathological findings are largely unknown. Indeed, only few studies have reported cranial nerve involvement in COVID-19—namely, ophthalmoplegia and facial nerve palsy in Miller Fisher syndrome,² isolated ophthalmoplegia,2, 3 acute vestibular dysfunction,⁴ and unilateral Tapia's syndrome.⁵

Between March and April 2020, we assessed four individuals who presented with fever, hyposmia, hypogeusia, and cough (three at IRCCS Mondino Foundation in Pavia, Italy, and one at ASST Bergamo Ovest in Romano di Lombardia, Italy). Within 2 weeks, they developed respiratory failure, which required hospital admission. Their nasopharyngeal swab tests were positive for SARS-CoV-2 RNA and chest CT showed lung ground-glass opacities in all patients. Within few weeks of hospitalisation, these patients needed invasive mechanical ventilation and tracheostomy in the local intensive care unit. When respiratory distress improved, and after weaning from respiratory support and tracheostomy removal, the patients had hoarseness, dysphagia, and tongue deviation. Brain MRI after gadolinium administration and CSF analyses, including isoelectric focusing, showed no abnormalities. Serological assays for anti-ganglioside antibodies and antibodies against Epstein-Barr virus, cytomegalovirus, Borrelia burgdorferi, Mycoplasma pneumoniae, and Campylobacter jejuni were negative. At about 20 weeks after the onset of respiratory symptoms, neurological examination showed a breathy voice, left-sided tongue deviation on protrusion, and unilateral or bilateral weakness of the soft palate, trapezius, and sternocleidomastoid in all patients. Pharyngeal sensation tested by means of a stick was preserved. The clinical course for each patient is reported in the appendix (pp 1–2). Electromyography of the muscles innervated by the pharyngeal, superior laryngeal, and recurrent laryngeal branches of the vagus nerve, and by the accessory and hypoglossal nerves, showed asymmetric patterns of acute or chronic neurogenic damage, or both. A hypoglossal nerve conduction study disclosed abnormalities consistent with the electromyography findings. Limb electroneurography, blink reflex, and facial nerve conduction studies were normal in all patients (appendix pp 2–3). At 3 months of follow-up, neurological symptoms were still present. Dysphagia and weakness of the soft palate, trapezius, and sternocleidomastoid improved in patients 3 and 4, and breathy voice and tongue deviation improved in patients 2 and 4. Electromyography showed unchanged chronic neurogenic impairment without evidence of acute denervation, which had been previously observed. The hypoglossal nerve conduction study showed only mild improvement.

Our patients with COVID-19 developed an isolated bulbar palsy, characterised by asymmetric selective involvement of the vagus, accessory, and hypoglossal nerves. This neurological condition might stem from a motor neuronopathy of medullary cranial nerve nuclei or from a lower cranial multiple neuropathy. The neuropathological evidence by Matschke and colleagues supports the involvement of the medulla oblongata,¹ which could have also contributed to the severe respiratory distress. Whether these findings reflect the direct (viral) or indirect (immune-mediated) effect of SARS-CoV-2 remains to be established. Notably, there was no clinical or electrophysiological worsening in our patients, and this finding argues against a progressive motor neuron disease, which could have been potentially triggered by chronic neuroinflammation. Isolated bulbar palsy might be a regional variant of Guillain-Barré syndrome associated with SARS-CoV-2 infection. Alternatively, a severe compression neuropathy of the lower cranial nerves might derive from abnormal head posture during a prone position manoeuvre, malposition or displacement of the tube, and overinflation of the cuff after airway manipulation during orotracheal intubation or tracheostomy. Finally, central and peripheral neurological involvement might coexist, as the damage of a neuronal soma can increase susceptibility to peripheral injury of the downstream axon.

The ongoing SARS-CoV-2 infection might increase the incidence of isolated bulbar palsy worldwide soon. These cases showed that isolated cranial nerve palsy can be encountered in patients with SARS-CoV-2 infection after intensive care. Long-term follow-up will provide further insights into the final prognosis in patients with this severe neurological complication.