COVID-19 and Neuromuscular Disorders

Cranial Neuropathy

The proposed mechanisms of central and peripheral nervous system involvement in SARS-CoV-2 are direct neuroinvasion, neurotropism leading to neurovirulence, and finally host’s adaptive immune response to infection. Neurologic complications seen in SARS-CoV and MERS-CoV are presumed to be from either hematogenous spread or retrograde neuronal dissemination. It has been documented that entry of COVID-19 spike protein into respiratory cells is mediated by ACE-2 receptors and also by binding to sialic acid moiety attached to cell surface glycoproteins and gangliosides. Costello and Dalakas favor an autoimmune mechanism for the neuropathies seen in COVID-19 infections. Cross reactivity between COVID-19 S-protein gangliosides and peripheral nerve glycolipids could also trigger an autoimmune reaction. The most plausible route of CNS infection by the virus is through the olfactory route, as olfactory bulb is not protected by the dura.

In a retrospective case series, taste and smell impairment were reported in 5.6% and 5.1%, respectively, in 214 patients admitted with Covid-19. In one large study of 204 mildly symptomatic patients, 64% reported olfactory dysfunction. A case-control study of confirmed COVID-19 infection showed smell dysfunction in 98% of patients, 35% being aware of their deficit, and the other 58% being either anosmic or microsmic. Sudden olfactory dysfunction (OD) has been recognized as a marker for COVID-19 infection. Anosmia and dysgeusia often happen in mild or asymptomatic cases. Olfactory receptor cells lack both ACE-2 receptors and cell surface protease TMPRSS2 gene that are necessary for direct invasion of viral particle. Olfactory ensheathing glial cells surround olfactory receptor cell axons and fila, and it appears that these cells may be responsible for ACE-2-independent viral transfer by the way of exosomes. Abnormal taste in the patients may also be attributable to the olfactory dysfunction rather than damage to the taste buds, as detecting flavor depends on retro-nasal olfaction. In a multicenter European study including 417 patients with confirmed COVID-19 infection of mild to moderate severity, 85.6% and 88% reported olfactory and gustatory dysfunction respectively. In 18.2% of the patients without nasal obstruction and rhinorrhea, almost 80% of them were either hyposmic or anosmic. An early olfactory recovery was reported in 44% of the patients. A proposed approach for the assessment and management of COVID-19-related olfactory dysfunction (OD) recommends a full otolaryngologic examination, which includes a three-pass naso-endoscopy when appropriate personal protective equipment is available, followed by CT to assess the paranasal sinuses, and MRI brain to examine brain and olfactory tracts if needed. MRI brain has been reported to demonstrate transient edema in the olfactory cleft, changes in the gyrus rectus, edema of olfactory cleft as well as olfactory atrophy. A psychophysical assessment using validated tests of odorants and tastants should complement the subjective assessment. Treatment may be needed if symptoms persist for more than 2 weeks. This includes olfactory training by sniffing specific odorants such as rose, lemon, cloves, and eucalyptus for 20 s each, at least twice daily for 3 months or longer. Other therapies which work in other postinfectious OD include intranasal vitamin A and systemic Omega-3 but these have not been tested in post-COVID-19 OD specifically. Whitcroft did not recommend corticosteroids, whether oral or intranasal, due to lacking evidence of benefit and potential harm. However, a small percentage of patients received nasal corticosteroids (8%) and oral corticosteroids (3%) as reported in the study by Lechien et al.

Isolated cases involving other cranial nerves have also been reported. In a large case series, one case of late optic neuritis was reported suggesting an immune-mediated etiology. Another patient has been described with unilateral ocular neuritis with optic disc edema along with panuveitis in the setting of COVID-19 infection.

Dinkin reported two patients with cranial neuropathies. One patient presented with cough, fever, and diplopia due to right abducens palsy with MRI evidence of enhancement of optic nerve sheaths and posterior Tenon capsules. Treatment included hydroxychloroquine for COVID-19 infection and oxygen after the nasal swab RT-PCR came back positive. The diplopia gradually improved over 2 weeks. The second case presented with unilateral ptosis, diplopia, and leg paresthesia, preceded by cough and fever. MRI brain showed left oculomotor nerve enhancement and enlargement. Intravenous immunoglobulins (IVIg) were given for presumed Miller-Fisher syndrome along with hydroxychloroquine, resulting in partial resolution of the deficits.

A case of isolated facial nerve palsy in a previously healthy 27-year-old male was reported by Goh et al. Soon after returning from Spain, the patient was admitted to a hospital, with flu-like symptoms and unilateral throbbing headache for 4 days without clinical evidence of meningitis. Left facial weakness was noted on day 6. Nasopharyngeal swab PCR was positive for SARS-CoV-2. Cerebrospinal fluid was noninflammatory and PCR for SARS-CoV-2 and other viruses was negative. MRI showed contrast enhancement of the left facial nerve. He was treated with prednisone, valacyclovir, and lopinavir/ritonavir.

Pellitero reported a case of acute vestibular dysfunction in a 30-year-old woman presenting with nausea, vomiting, and disequilibrium 3 weeks after developing anosmia and ageusia. Her RT-PCR for COVID-19 was positive on admission. Her MRI of the brain was normal, and she improved with vestibular suppressants and antiemetics.

Anterior Horn Cell/Motor Neuron Disease

There are no reports of acute presentation of anterior horn cell dysfunction similar to West Nile poliomyelitis. A case series from Scotland did not report any change in the new diagnosis of motor neuron disease (MND) during the COVID-19 pandemic and reported two cases with MND with confirmed or suspected COVID-19 infection, who died. Another case report described two patients with MND on noninvasive ventilatory support at baseline, with multifocal pneumonia. One patient with confirmed COVID-19 recovered after treatment with remdesivir and solumedrol and the other patient with suspected for COVID-19 infection recovered after treatment with antibiotics and increased respiratory support.