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ORIGINAL ARTICLE
Year : 2022  |  Volume : 25  |  Issue : 7  |  Page : 1061-1068

Evaluation of neurology consultations in a COVID-19 pandemic hospital, A retrospective study


Department of Neurology, Saglik Bilimleri University, Konya City Hospital, Konya, Turkey

Date of Submission22-May-2021
Date of Acceptance10-May-2022
Date of Web Publication20-Jul-2022

Correspondence Address:
Dr. Z B Gunduz
Department of Neurology, Saglik Bilimleri University, Konya City Hospital Akabe 42020 Karatay/KONYA
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_1539

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   Abstract 


Background: Affinity of coronavirus disease to the central nervous system is not well known. Aim: We aimed to share the data of COVID-19 patients with neurological complaints in a pandemia hospital. Material and Method: Consultation results requested from the neurology clinic of Konya Meram State Hospital were retrospectively examined. PCR test positive patients, PCR negative patients with positive clinical, laboratory and radiological findings with COVID-19 were evaluated. Age, gender, history of neurological diseases, and neurological symptoms were recorded. Results: The reason for consultation was acute neurological symptom in 96 (84.2%) patients, counseling for treatment in chronic disease in 15 (13.2%) patients, and worsening in chronic disease in 3 (2.6%) patients. As neurological disorders, 22 (19.3%) had a history of previous stroke, 10 (8.8%) had dementia, 4 (3.5%) had epilepsy, 4 (3.5%) had Parkinson's disease, 3 (2.6%) had multiple sclerosis, 2 (1.8%) had myasthenia graves, and 1 (0.9%) had restless legs syndrome respectively. The most common reason for requesting consultation was changes in consciousness (56.1%). Of the 114 patients who requested neurology consultation, 65 (57%) were discharged, 49 (43%) were died. Conclusion: The change in consciousness was the reason in more than half of the patients who requested neurology consultation during COVID-19 follow-up. Impaired consciousness in a patient with COVID-19 may indicate a poor prognosis. If the studies planned in the near future can shed light on the cause of the unconsciousness developing in COVID-19, it will be promising in terms of treatment plans to reduce mortality.

Keywords: Consultation, COVID-19, mortality, neurology, unconsciousness


How to cite this article:
Gunduz Z B. Evaluation of neurology consultations in a COVID-19 pandemic hospital, A retrospective study. Niger J Clin Pract 2022;25:1061-8

How to cite this URL:
Gunduz Z B. Evaluation of neurology consultations in a COVID-19 pandemic hospital, A retrospective study. Niger J Clin Pract [serial online] 2022 [cited 2022 Aug 19];25:1061-8. Available from: https://www.njcponline.com/text.asp?2022/25/7/1061/351448




   Introduction Top


In December 2019, a new coronavirus that causes pneumonia and severe acute respiratory syndrome appeared in Wuhan, China, which spread rapidly and resulted in an epidemic, and was declared as a pandemic by the World Health Organization on March 11, 2020. As the data about the disease increased, the opinion that COVID-19 was not limited to pneumonia and severe acute respiratory syndrome and that the central and peripheral nervous system was affected by the infection like many other systems gained weight. Although information on this new infectious agent is limited, it was known that the central nervous system was either determined as a direct target for many infectious diseases or was secondarily affected by the infection, and the affinity of this new disease to the nervous system did not surprise the medical world.[1]

Among the neurological symptoms of COVID-19, dizziness, headache, myalgia, and loss of sense of smell and taste are common, but these complaints, which can also be seen during other infections, are not specific for COVID-19. As per the case reports of COVID-19 patients with severe nervous system findings such as polyneuropathy, myositis, cerebrovascular diseases, encephalitis, and encephalopathy, the neurotrophic effect of this viral agent comes to the fore. Nevertheless, it is not possible to distinguish between causal relationship and incidental comorbidity with available data.[1]

Although it is not yet fully understood how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reaches the nervous system, neuronal retrograde spread and hematogenous spread through peripheral nerves are blamed. The assumptions about SARS-CoV-2 neuroinvasivity are based on animal model data, both of which have been demonstrated in SARS and Middle East respiratory syndrome (MERS) epidemics caused by coronaviruses of similar nature in 2002 and 2012, respectively. All these pathogens use angiotensin-converting enzyme 2 (ACE2) to gain access to target cells. ACE2 receptors are found in nervous system tissues, endothelial cells, and many other tissues. Compared to previous coronaviruses, the SARS-CoV-2 spike glycoprotein shows a higher affinity for the ACE2 receptor and is therefore thought to have higher neuroinvasive potential.[2]

The view that SARS-CoV-2, which can present with respiratory tract infection or gastroenteritis manifestation, can reach the central nervous system through the olfactory nerve and intestinal vagal afferents, is the hypothesis explaining the neuronal retrograde transmission to the central nervous system.[2] However, the virus does not only use the olfactory nerve as a passageway, but the reduction or complete loss of sense of smell in most patients is one of the first signs of the disease. Involvement of the olfactory nerve is the first finding that questions the relationship of the nervous system with the virus. Partial or complete recovery of anosmia or hyposmia may take months, and studies have pointed out that only half of the patients recovered completely, even 8 months after diagnosis.[3] These data, which point to viral damage of the nervous system, increase concerns due to the lack of regeneration ability of this system.

As the clinical findings of COVID-19 differ between individuals, it is not possible to predict in which patients neurological symptoms will occur. In this article, it is aimed to share the data of COVID-19 patients with neurological complaints in the literature.


   Materials and Methods Top


The retrospective study protocol was approved by the Saglik Bilimleri University Medical Faculty Ethics Committee (protocol number: 2021/1:35; date: January 8, 2021). In the study, the consultation results requested from the neurology clinic of Konya Meram State Hospital between March 1, 2019, and December 1, 2020, were retrospectively evaluated. In addition to the patients diagnosed with polymerase chain reaction (PCR) test positivity, patients whose clinical, laboratory, and radiological findings were found to be compatible with COVID-19 even though the PCR test was negative were also included in the study. Patients who were hospitalized with a pre-diagnosis of COVID-19, but whose PCR test was negative and who were transferred to non-pandemic hospitals by excluding COVID-19 with clinical, laboratory, and radiological findings in their follow-up were excluded from the study. The condition of being evaluated by a neurology physician was sought as the inclusion criteria for the study. Patients whose consultation, laboratory, and radiology findings and epicrisis information could not be reached, outpatients who were consulted from the emergency service or outpatient clinic, and those who were referred to external centers were excluded from the study. Descriptive analyses were used for statistics.


   Results Top


The ages of 114 patients included in the study ranged from 22 to 92; those with a median value of 72–63 (55.3%) of the patients were men and 51 (44.7%) were women. The PCR test of 96 (84.2%) of the inpatients with the diagnosis of COVID-19 was positive, 18 (15.8%) PCR tests were negative, but the clinical and laboratory findings were found to be compatible with COVID-19 by thorax computed tomography (CT) and the treatment was arranged. Thorax CT was performed in 110 (96.5%) of the patients. Of these, 100 (87.7%) were reported to be compatible with viral pneumonia or COVID-19, 2 (1, 8%) were suspected to have COVID-19, 4 (3.5%) were compatible with mixed-type pneumonia, and 4 (3.5%) were reported as normal. Of the consultations, 3 (2.6%) were requested from the outpatient clinic (followed by hospitalization later), 29 (25.4%) from the emergency room, 59 (51.8%) from the services, 23 (20.2%) from the intensive care units, and 11 (9.7%) were intubated. The general condition of 23 (20.2%) of the patients was good, that of 64 (56.1%) of them was moderate, and that of 27 (23.7%) of them was bad [Table 1].
Table 1: Patient characteristics

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The reason for consultation was acute neurological symptom in 96 (84.2%) patients, counseling for treatment of chronic disease in 15 (13.2%) patients, and worsening of chronic disease in 3 (2.6%) patients [Table 2].
Table 2: Consultation Evaluation

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History of neurological disease was not found in 68 (59.6%) of patients before evaluation. As neurological disorders, 22 (19.3%) had a history of previous stroke, 10 (8.8%) had dementia, 4 (3.5%) had epilepsy, 4 (3.5%) had Parkinson's disease, 3 (2.6%) had multiple sclerosis, 2 (1.8%) had myasthenia gravis (MG), and 1 (0.9%) had restless leg syndrome [Table 2].

Whereas 16 (14%) of the evaluated patients were diagnosed with COVID-19 during admission to the hospital with neurological symptoms, 80 (70.2%) of them had neurological symptoms following the diagnosis of COVID-19 and 18 (15.8%) had no acute neurological complaints [Table 2].

The most common reason for requesting consultation was changes in consciousness in more than half of the patients (56.1%). Of the 64 patients who were consulted for altered consciousness, 27 (42.2%) had delirium, 26 (40.6) encephalopathy, 8 (12.5%) had acute cerebrovascular disease, and 3 (4.7%) had seizures [Table 2]. Brain CT and/or diffusion magnetic resonance imaging (MRI) were performed in all of these patients.

Of the 114 patients who requested neurology consultation, 65 (57%) were discharged and 49 (43%) died. The reasons for neurology consultation requested in 49 patients with exitus were as follows: 28 (57.2%) patients presented with impaired consciousness, 9 (18.4%) patients had agitations, 4 (8.2%) patients had seizures, 3 (6.1%) patients had weakness, 2 (4.1%) patients underwent chronic neurological disease treatment counseling, 1 (2%) patient had speaking impairment, 1 (2%) patient presented with involuntary movement, and 1 (2%) patient presented with dizziness [Table 3].
Table 3: Neurological complaints of patients and their state of discharge/death

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Two (4.1%) acute ischemic stroke and 3 (6.1%) acute hemorrhagic stroke patients primarily died due to neurological disease, and 2 (4.1%) died due to the combination of neurological disease and COVID-19 with the diagnosis of acute ischemic stroke. In the other 42 (85.7%) patients, the cause was COVID-19 and related complications [Table 4].
Table 4: Death–disease relationship

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Acute arterial ischemic stroke was found in 17 patients [Figure 1], hemorrhagic stroke in 3 [Figure 2], and venous infarction due to sinus vein thrombosis in 1 [Figure 3] patient. Eighteen patients had sequelae of cerebrovascular disease (CVD) without acute stroke. Four of the patients with acute CVD had a history of stroke in the past. Radiological imaging of the patients diagnosed with acute ischemic stroke revealed anterior circulation infarction in 13, posterior circulation infarction in 2, and multiple embolic acute ischemia in 2 patients. Only 2 of the patients diagnosed with acute ischemic stroke were in the hyperacute period, for which intravenous thrombolytic therapy (IV TPA) could be applied, but 1 of them could be treated with IV TPA, whereas the other had contraindications. For arterial stroke, 3 patients had essential hypertension, 1 patient had diabetes mellitus, and 1 patient had a history of heart valve replacement, whereas the other patients had more than one risk factor. Because carotid–vertebral imaging and advanced cardiac examination were planned under elective conditions after isolation in this patient group, more detailed information about the etiology could not be obtained.
Figure 1: (a-d) Diffusion MRG in acute ischemic stroke

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Figure 2: (a-c) CT in acute hemorrhagic stroke

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Figure 3: Sinus venous thrombosis (a) cranial MRI, (b) MRI venography

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In patients with acute hemorrhagic stroke, 1 had malignant hypertension, 1 had anticoagulant use, and 1 had aneurysm as risk factors. As the bleeding localization, 1 basal ganglion, 1 lobar, 1 aneurysmal subarachnoid hemorrhage were detected [Table 5].
Table 5: Characteristics of stroke patients receiving COVID-19 treatment

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Delirium developed during follow-up in 8 of 10 patients who were diagnosed with dementia before hospitalization. Delirium developed in 1 out of 4 Parkinson's disease patients. No change in antiparkinsonian treatment was required in any of the Parkinson's disease patients [Table 6].
Table 6: Data on other chronic neurological diseases except acute stroke

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Four of the patients were diagnosed with epilepsy before their hospitalization, 3 of them did not change the frequency and treatment of seizures, 1 had an increase in the frequency of seizures and the dose of the antiepileptic treatment he used was increased. Three patients were evaluated with the complaint of active seizures during their follow-up, whereas there was no diagnosis of epilepsy before admission; 1 of them was associated with metabolic disorders, and they followed up without antiepileptic treatment. Antiepileptic treatment was given 2 of them. None of them were diagnosed with status epilepticus. No acute pathology was found in the CT and diffusion MRI of the newly diagnosed seizures [Table 6].

Both of the patients diagnosed with MG had a history of thymectomy, no immunosuppressant use, and both had mild weakness and fatigue. In one, only increasing the dose of pyridostigmine was sufficient, and there was no need for further treatment in terms of COVID-19, but antibiotic treatment was continued after antiviral therapy. In the other, due to the severe lung involvement of COVID-19, intravenous immunoglobulin administration was needed. Both were discharged [Table 6].

One of the multiple sclerosis (MS) patients was in the relapsing remitting form (RRMS) and was using fingolimod; one of them was in the secondary progressive form (SPMS) and was using ocrelizumab; the other was in the primary progressive form (PPMS) and was not using any treatment. None of them had new neurological complaints or showed worsening of neurological findings accompanying COVID-19. Pulse steroid (methylprednisolone) therapy was given to a patient with secondary progressive MS due to COVID-19. Patients were discharged after treatment [Table 6].


   Discussion Top


At the beginning of the COVID-19 pandemic caused by SARS CoV2 (new corona virus), it was thought that the target of the virus was the respiratory tract, but it did not take much time to identify clinical reflections of other systems. Because the cause–effect relationship or pathogenesis could not be revealed, these reports took their place as “COVID-19 association” in the literature.

Neurological symptoms have been described in approximately one-third of hospitalized COVID-19 patients.[4] Some of these symptoms are neurologically nonspecific as in most viral infections, headache, dizziness, and myalgia are common among the symptoms of COVID-19.[5] These symptoms, which generally regress and recover completely with the treatment of the infection, remain in the shadow of the other flu symptoms in the acute period and are not found to be odd by the patient or the physician who follows with them. For this reason, the number of patients requested for neurology consultation with isolated headache or dizziness is limited in our study. The easy access to diffusion MRI and brain CT to rule out acute pathology is another reason why patients with these complaints continue to be treated without consulting a neurologist during the pandemic period. Although it was a common finding during COVID-19,[3] anosmia was not a reason for consultation in any patient.

In another group with neurological symptoms, a neurological pathology has been revealed, but the cause and effect relationship with COVID-19 has not been revealed. Cerebrovascular diseases are a group whose association with COVID-19 is frequently revealed, but the causality relationship has not been clarified.

In our study, ischemic stroke was detected in 17 patients, but elective examinations such as echocardiography and carotid–vertebral Doppler ultrasonography were delayed after the infection treatment due to the necessity of isolation, so the data we have are insufficient to reveal the etiology. The data on the relationship between COVID-19 and stroke were limited only to cases where the coexistence of COVID-19 and stroke was shared at the onset of the pandemic.[6] Similar case reports formed the basis for various hypotheses but were not sufficient to reveal cause–effect relationships. Recently, data on large case series have begun to be shared, but the only thing that can be clearly expressed about these two diseases was that their coexistence increased mortality in stroke.[7]

There are publications stating that there is a relative increase in spontaneous intracranial hemorrhage among all stroke types during the first peak of the pandemic, but it was also pointed out in these publications that most of the patients had at least one risk factor for intracranial hemorrhage.[8] In our series, intracranial hemorrhage was detected in 3 (14.3%) of 21 patients diagnosed with acute cerebrovascular disease, and it was observed that there was a risk factor for intracranial hemorrhage in all patients.

There are reported cases of arterial and venous thromboembolism attributed to irregular coagulopathy, widespread systemic inflammation, and endothelial dysfunction associated with severe COVID-19. In the case series diagnosed with sinus vein thrombosis during the course of COVID-19, the cases were interpreted as association, not cause–effect relationship.[9] In our series, there was only one patient with venous infarction, an accompanying 35-week pregnancy was present, and the patient who delivered a healthy baby after cesarean was discharged with regulated treatment.[10]

The negative impact on cognitive functions observed during the course of COVID-19 is an issue that should be emphasized. Although various data have been published on the picture of encephalopathy, which attracts attention especially in the acute period, its pathophysiopathology is not fully understood. Although external factors such as intubation, the use of sedative–hypnotic and anticholinergic agents, and unstable comorbidities in intensive care patients, as well as increased social distances due to mandatory isolation, are blamed in the etiology, it is thought that specific factors related to SARS-CoV-2 that have not yet been revealed may contribute to encephalopathy. In a study in which COVID-19 patients with encephalopathy were evaluated, the fact that most of the patients were intubated due to the severity of pneumonia and acute respiratory distress syndrome supports the hypothesis that encephalopathy may result from hypoxemia.[11]

Studies focusing on the neurological features of COVID-19 suggest that confusion occurs in 20–30% of hospitalized patients, reaching 60–70% in severe forms of the disease. Older adults are more prone to the development of confusion and delirium and are higher predisposing risk factors prior to dementia, advanced age, visual and hearing impairment, and polypharmacy.[12]

It is known that most of the patients who had COVID-19 disease with severe acute respiratory distress syndrome clinic continued to show impairments in memory, attention, concentration, or mental processing speed for the following year,[13] but how COVID-19 exerts its negative effects on cognition has not yet been elucidated.

In our study, all patients with impaired consciousness were evaluated using the box and block test (BBT) and diffusion MRI, but contrast-enhanced cranial MRI and cerebrospinal fluid (CSF) examinations were not performed. However, the series in which the cases of encephalopathy with CSF examination in patients with COVID-19 are shared agree that the virus will generally not be detected in the CSF by reverse-transcriptase-PCR and pleocytosis will not be detected.[11],[14]

MG is a muscle disease that exacerbates with many factors, especially infections. During these exacerbations, the greatest concern is stiffness of the respiratory muscles. Myasthenic crisis is characterized by severe bulbar dysfunction and/or respiratory failure, which in most cases may require mechanical ventilation and intensive care admission. Plasmapheresis or polyvalent immunoglobulins (IVIGs) are used in the treatment of myasthenic crisis. Close follow-up is required for the mechanical ventilation decision. The dose of acetylcholinesterase inhibitors may increase in mild symptoms that do not reach the size of myasthenic crisis, but it should be kept in mind that these drugs may mimic a myasthenic crisis in overdose.[15] In cases where acetylcholinesterase inhibitors are not sufficient, steroids and immunosuppressive therapy can be planned. Considering that steroids may temporarily increase muscle weakness when first started, a gradual dose increase is recommended. Especially, the association of COVID-19 with severe respiratory failure and MG is a serious concern for the physician. These patients need to be followed up with a specialist team. Both of our patients had a history of previous thymectomy. Whereas it was sufficient to increase the dose of pyridostigmine in the patient with a slight increase in symptoms, the other intensive care unit was followed up with IVIG treatment. These two patients were not intubated, and both of them were discharged after completing their treatment.

Due to the fact that it is an autoimmune disease and the spread of immunosuppressive treatments, it was a curious matter how COVID-19 will progress in patients with multiple sclerosis. Data on this subject are increasing day by day. There are publications stating that there is no significant difference in the severity of SARS-CoV-2 infection according to the age of the patient, the duration of the disease, the degree of disability (EDSS), lymphocyte count, or the type of disease-modifying therapies (DMT) used.[16] Although the number of our patients was small, the presence of MS in all three of our patients and the treatments they used did not negatively affect the prognosis of COVID-19. If MS patients need to be followed up by physicians who are not neurologists due to COVID-19, it is recommended to seek neurology opinion in terms of drug interactions and possible side effects due to DMT used.

Another neurological patient group that should be considered in terms of drug interactions is epilepsy patients. Antiepileptics, most of which are metabolized through the liver, are very susceptible to drug interactions due to enzyme inhibition/induction. They may affect the levels of the drugs used together, and they may be affected by these drugs and may go beyond the therapeutic dose range, so regulation of drug doses may be required. It should also be kept in mind that some drugs may lower the seizure threshold in patients with epilepsy.[17] Acutely developing seizures and status epilepticus (SE) in patients with COVID-19 may be caused by febrile state, hypoxia, or metabolic disorders. However, according to available data, such etiologies are rare and usually give a good response to treatment. In the subgroup of patients whose etiology could not be established, SE was demonstrated to begin a few days after the onset of systemic symptoms and respond worse to treatment. Most of the data presented belong to convulsive SE. Patients diagnosed with COVID-19 often have limited access to diagnostic investigations, including EEG, due to the contagiousness of the disease, which may cause nonconvulsive seizures to be overlooked.[18] Increase in seizure frequency was observed in only one of our four patients diagnosed with epilepsy; status epilepticus was not considered, and increasing the antiepileptic dose was sufficient for seizure control. The reason for new onset seizures in one of the 3 patients evaluated was that metabolic imbalance and antiepileptic treatment was not initiated in this patient. The other two patients had recurrent seizures requiring antiepileptic treatment.

In our study, the cause of death of 5 of 49 patients whose follow-up resulted in death was directly related to stroke, whereas 2 of them were showed coexistence of stroke and COVID-19; due to death, the effect of neurological disease could not be revealed in other deaths; it was thought to be due to COVID-19 and its complications. Other neurological diseases could not be associated with deaths. Follow-up of all 3 patients diagnosed with hemorrhagic stroke resulted in death. However, because none of the deceased were autopsied, these should be considered as the clinician's interpretation.


   Conclusion Top


In our study, the acute neurological pictures observed during COVID-19 and the data to evaluate the interaction of this infection with chronic neurological diseases were shared. As stated in previous publications, the data obtained are not sufficient to establish the cause–effect relationship of acutely developing neurological diseases such as cerebrovascular disease with COVID-19. It should be kept in mind that in people with chronic neurological diseases, individual regulation may be required considering the drug interaction in COVID-19 treatment regulation.

The striking point in the data we have obtained is that the complaints concentrate around unconsciousness. Our data reveal that in more than half of the patients who requested neurology consultation during the COVID-19 follow-up, the change in consciousness was the reason for consultation, and in most of these patients, no acute pathology was detected in the BBT and diffusion MRI. We think that impaired consciousness in the patient with COVID-19 may indicate a poor prognosis because neurology consultation was requested, and the reason for consultation was unconsciousness in four out of five patients who died.

If the studies planned in the near future can shed light on the cause of the unconsciousness developing in COVID-19, it will be promising in terms of treatment plans to reduce mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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