In March of last year Dr. A. Jimenez, neurologist attached to the Clinical Neurology Program of the Neurology Service, wrote an entry in our blog about COVID19 and neurology, nowadays we have much more information and for this reason he has written an update.
Neurology and COVID19
NEUROLOGICAL MANIFESTATIONS OF SARS-CoV-2 VIRUS INFECTION
Infection with the new SARS-CoV-2 coronavirus produces a series of clinical manifestations that fall under the term COVID-19.
Initial symptoms usually consist of nasal congestion, loss of smell, dry cough, muscle aches and fever. In most patients the disease has a limited and benign course. However, in some cases the disease follows an aggressive course, characterized by progressive respiratory distress and a severe inflammatory response, necessitating advanced supportive measures such as mechanical ventilation.
As we have gained experience with COVID-19 we have learned that a high percentage of patients develop significant neurological symptoms.
Some of these manifestations were to be expected, as they occur routinely in the context of other viruses and severe illnesses. For example, most patients requiring intensive care, not only for COVID-19, develop acute confusional syndrome (acute encephalopathy), characterized by fluctuations in alertness, disorientation, inattention, confusion and, in some cases, psychomotor agitation, visual hallucinations and delusions (e.g. false recognition of people or places). A very frequent finding in critically ill patients is also the development of diffuse neuromyopathy, which presents with generalized weakness and has a multifactorial origin (immobility, inflammatory response, muscle blocking agents…).
As a peculiarity, in some patients the predominant symptom of COVID-19 is headache. Sometimes they even have associated transient neurological symptoms (e.g. sensory symptoms, visual disturbances), similar to those described by patients with migraine with aura. In most cases in which cerebrospinal fluid (CSF) has been analyzed, the virus has not been detected, so it is thought that it may depend on the systemic inflammatory response (e.g. increased cytokines).
As noted above, loss of smell and taste alterations are early manifestations of the disease and, in general, their intensity is disproportionate to the degree of nasal congestion. These symptoms can be explained by a lesion of the olfactory epithelium, but several neuroimaging studies have shown that lesions can also occur in the olfactory bulbs and other adjacent regions of the nervous system.
The incidence of cerebral infarcts and hemorrhages in COVID-19 is higher than that observed in other viral infections. In all likelihood, this particular susceptibility to stroke, even months after the acute illness has passed, depends on a combination of factors, including the prothrombotic state associated with inflammatory processes, dysfunction of the renin-angiotensin system (the virus uses angiotensin-converting enzyme 2 to gain access to the interior of cells), possible involvement of the vascular endothelium and the development of emboligenic cardiac alterations (e.g. myocarditis, arrhythmias).
Less frequently, inflammatory conditions with central (encephalitis, cerebellitis, myelitis) or peripheral (polyradiculitis or Guillain-Barré syndrome) nervous system involvement have been detected. The available data suggest that the main pathogenic mechanism in these cases is autoimmune, whereas direct injury by the virus seems to be an infrequent or secondary phenomenon. However, a recent article, based on a series of autopsies, suggests that the virus may frequently gain access to the central nervous system via the olfactory pathways.
Finally, follow-up of patients with COVID-19 has shown that in some cases the recovery process can be prolonged(post-COVID syndrome). These patients develop symptoms similar to those described in the context of chronic fatigue syndrome or fibromyalgia. Cognitive complaints (e.g. memory lapses) are also common. The pathogenic mechanism is uncertain, but by analogy with other similar conditions, psychological factors, autoimmune phenomena and even persistent infection may be involved.
Personal experience
In my experience I have had the opportunity to evaluate several patients with COVID-19 and neurological manifestations. In general, the most severe patients, admitted to the intensive care unit, presented acute encephalopathy (confusional syndrome) and neuromyopathy of the critically ill patient of multifactorial origin.
An elderly patient developed Guillain-Barré syndrome two weeks after having mild symptoms associated with COVID-19. And a middle-aged patient debuted with an aggressive course of limbic encephalitis, requiring treatment with steroids, immunoglobulins and rituximab. Finally, we are receiving an increasing number of patients with persistent symptoms in neurology consultations after COVID-19.
The neurological assessment of patients with COVID-19
The neurological assessment of patients with COVID-19 begins with anamnesis and physical examination. In the anamnesis or interrogation, the patient’s symptoms are collected, including their characteristics, intensity and temporal profile. In the physical examination, the various functions of the nervous system (e.g. mental status, cranial nerves, strength, sensitivity, reflexes, coordination, gait) are systematically analyzed. Depending on the clinical data, a decision is made as to whether an additional examination is necessary (e.g. neuroimaging tests, electroencephalogram, electromyogram, CSF analysis).
Treatment of neurological problems
The treatment of neurological problems associated with COVID-19 is based on the same principles as those applied to other patients, since no specific treatments are currently available for these cases. In particular, patients with stroke and COVID-19 should be managed following the guidelines and protocols used for stroke patients in general, and patients with Guillain-Barré syndrome are usually treated with intravenous immunoglobulins.
Patients with critical patient neuromyopathy require physiotherapy, while those with cognitive symptoms may benefit from a neuropsychological rehabilitation program. The treatment of encephalitis and myelitis is more questionable, but with the possibility of an autoimmune origin they are usually managed with steroids or immunoglobulins. It is also important to pay attention to the affective symptoms that may appear in this context and that may require pharmacological treatments (e.g. antidepressants) or psychotherapy.
For additional information on the neurological problems associated with COVID-19 we recommend accessing the articles “Neurological associations of COVID-19”(https://doi.org/10.1016/S1474-4422(20)30221-0) and “Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019. A Review”(https://jamanetwork.com/journals/jamaneurology/fullarticle/2766766).
