Neurological complications are not as rare as previously believed and both central and peripheral nervous system are being affected by COVID-19 either directly or indirectly . Complications involving the peripheral nervous system are mostly olfactory and gustatory in nature . Few reports have surfaced mentioning GBS and other neuromuscular disorders . Another case series of 214 patients showed that symptoms of peripheral nervous system had an occurrence of 8.9% . However, peripheral neuropathy has a rare association with COVID-19 with an estimated prevalence of less than 1% in a recent study . Pakistan has reported an approximate 18.9% cases with neurological complications; however, no case of neuropathy has been reported from here .
Here we have discussed a case of a middle-aged man who developed axonal mononeuropathies as a sequela of COVID-19, an exceedingly rare complication seen in this disease. Majority of the case series and studies have shown that symptoms of peripheral neuropathy appeared along with the respiratory symptoms [7, 11]. One study has reported that the neurological symptoms preceded the respiratory symptoms . However, some case reports and studies showed that neuropathy started after the respiratory symptoms started resolving as in our case [4, 13, 14]. Nonetheless, most of the cases with these symptoms of peripheral neuropathy had prolonged intensive care stay which was not present in our case [4, 7].
The presentation of mononeuropathies in COVID-19 patients has a vast spectrum. Patients have presented with quadriparesis, paraplegia, symmetrical and asymmetrical weaknesses , neuropathic pain , fatigue and myalgia , and numbness . Moreover, Literature review shows that peripheral neuropathy in COVID-19 patients can be of both axonal and demyelinating type. The largest case series of 14 COVID-19 patients with mononeuropathies had characteristic axonal type of pathology , while another case series of three patients reported demyelinating lesions . Three studies had no NCS/EMG done due to improvement in symptoms and COVID-19 isolation policies [11,12,13]. Our patient presented with asymmetrical weakness localized to lower limbs characterized as axonal mononeuropathies and also had no associated pain or other sensory symptoms, nor had any symptoms of dysautonomia. Even though, our patient had no sensory system, NCS revealed an absent left superficial peroneal response on sensory nerve conduction studies. It is very common that the clinical exam does not always match the nerve conduction studies. To give an example, in Guillain Barre syndrome the patient has no abnormalities on the clinical exam; however, the sensory NCS are found to be abnormal frequently . Similarly, in patients with lumbar radiculopathy, findings of clinical exam, NCS and radiological investigations do not always match .
The mechanism behind peripheral neuropathy remains unclear. There are two school of thoughts concerning the mechanism behind peripheral neuropathy in COVID-19 patients. The axonal or demyelinating lesion may be depending upon the mechanism behind the injury. Immune-mediated mechanism is one of the hypothesized theories to be behind peripheral neuropathies in cases of COVID-19. It has been seen that the COVID-19 virus shares two hexapeptides with human shock proteins 90 and 60. Both proteins have immunogenic potentials, leading to slow damage of the axons and causing axonal mononeuropathies as in our case and three other studies [3, 13, 15]. The other theory has been hypothesized by Guadarrama-Ortiz et al., stating that vascular, thrombotic, ischemic, and direct nerve effects driven by SARS-CoV-2 can also lead to neuropathy in COVID-19 patients [14, 16]. The same study also states that early neurological signs may be indicative of a direct injury on the peripheral nerves from the virus. In our case, however, this may not be the mechanism behind as the symptoms of mononeuropathies appeared after the resolution of respiratory symptoms.
It is essential to ascertain the cause of mononeuropathies before associating it with COVID-19 infection. Diabetes and critical illness neuropathy remain important causes. Literature shows that distal symmetric sensorimotor polyneuropathy is the most common form of neuropathy seen in diabetes because of “dying back” axonal degeneration . Another characteristic finding seen in diabetic neuropathy is the involvement of sural and tibial nerves. Furthermore, the incidence of neuropathic symptoms is more likely to be increased with uncontrolled and long duration of diabetes [20, 21]. Critical illness neuropathy is a diffuse process; hence, findings are expected to be seen symmetrically. As seen in diabetes, sural nerve involvement is also characteristically seen in critical illness neuropathy . High inspiratory pressures, increased ventilator days and longer intensive care stay are also important characteristics of critical illness neuropathy . However, the characteristics seen in these two causes are quite different than our case as diabetes was well controlled and short of duration and the patient had no stay in intensive care, while NIV was only applied for 48 h. Furthermore, findings on nerve conduction studies were of asymmetrical nature and spared the sural nerves.
Treatment in our case was extensive physical therapy and rehabilitation. Six months later he showed remarkable improvement. This is in line with majority of the cases reported in literature which emphasize upon the importance of effective rehabilitation in these patients. Plasma exchange has also helped in rapid resolution of neurological as well as respiratory symptoms .