|Year : 2022 | Volume
| Issue : 6 | Page : 1047-1055
Neurological manifestations in COVID-19 in three waves of the pandemic: An inpatient study from India
Rahul Kulkarni, Dulari Gupta, Shripad Pujari, Vishal Deshpande, Pravin Naphade, Rushikesh Deshpande
Department of Neurology, Deenanath Mangeshkar Hospital and Research Center, Pune, Maharashtra, India
|Date of Submission||26-Feb-2022|
|Date of Decision||08-Mar-2022|
|Date of Acceptance||20-Mar-2022|
|Date of Web Publication||03-May-2022|
Department of Neurology, Deenanath Mangeshkar Hospital and Research Center, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Though severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) virus primarily affects respiratory system, neurological involvement is well known. Aims: To describe the neurological manifestations of coronavirus disease 2019 (COVID-19) during three waves of the pandemic. Methodology: This was an ambispective observational single-centre study to describe the neurological manifestations of COVID-19 infection among inpatients from a tertiary care referral centre in Western India from March 2020 to January 2022. Results: Out of 14,822 patients admitted with COVID-19, 307 (2.07%) had neurological manifestations. Neurological manifestations were seen in 1.87% in first wave (onset to 10 Feb 21); 2.37% in second wave (Feb 11, 2021 to Dec 31, 2021) and 6.26% in third wave (Jan 1, 2022 to Jan 31, 2022). The most common neurological manifestations were encephalopathy (34.5%), ischemic stroke (32.1%), and acute symptomatic seizures (8.8%). Encephalopathy (p = 0.028) was more common in first wave while seizures were more common in third wave (p = 0.001). In patients with encephalopathy, hypoxia (p = 0.0001), shock (p = 0.001), renal involvement (p = 0.002), and sepsis (p = 0.033) were associated with higher mortality; while those with no systemic involvement had better survival (p = 0.0001). Among patients with ischemic stroke, 32.1% did not have any traditional vascular risk factors. These patients were 9 years younger and required 6 days less hospitalization than patients of stroke with vascular risk factors. Conclusion: SARS-CoV-2 produces many central and peripheral nervous system manifestations. Encephalopathy was more common in first wave while acute symptomatic seizures were more common in third wave. Encephalopathy was most common neurological manifestation with progressively higher mortality with increased number of systemic comorbidities. Ischemic stroke was seen in patients who had vascular risk factors as well as in patients without them.
Keywords: Acute ischemic stroke, COVID-19, encephalopathy, neurological manifestations
|How to cite this article:|
Kulkarni R, Gupta D, Pujari S, Deshpande V, Naphade P, Deshpande R. Neurological manifestations in COVID-19 in three waves of the pandemic: An inpatient study from India. Ann Indian Acad Neurol 2022;25:1047-55
|How to cite this URL:|
Kulkarni R, Gupta D, Pujari S, Deshpande V, Naphade P, Deshpande R. Neurological manifestations in COVID-19 in three waves of the pandemic: An inpatient study from India. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Jan 29];25:1047-55. Available from: https://www.annalsofian.org/text.asp?2022/25/6/1047/344687
| Introduction|| |
Coronavirus disease 2019 (COVID-19) pandemic caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves not only respiratory system but also other systems as well including the nervous system. After initial reports from Wuhan, China, multiple reports and meta-analysis on neurological manifestations have been published.,,,,,,,,,,, The neurological manifestations were initially described as symptoms. With better understanding of the clinical presentations, subsequent publications described them as syndromes.
The neurological manifestations are seen involving almost all portions of neuroaxis including encephalopathy, strokes, neuropathies, and encephalitis. Nervous system involvement can be because of systemic involvement, metabolic impairment, sepsis, immune mechanisms, pro-thrombotic state, endothelial inflammation, and direct tropic effects of the virus itself. There may be regional differences in neurological manifestations due to different host, viral strain, and environmental conditions. During the course of the pandemic, different viral strains have been dominant, most notably delta variant (B 1.617.2) in the second wave and omicron (B.1.1.529) in the third wave in India. It is now a known fact that, invasive fungal infections were a very prominent feature in the second wave.
We describe the neurological manifestations caused by COVID-19 in our cohort of patients since the inception of the pandemic in India and compared these among the three waves.
| Methodology|| |
This was an ambispective observational study conducted in a multi-speciality tertiary care private hospital in Pune, Western India. Retrospective data were collected from March 2020 to April 2021 and prospective data were collected thereafter till January 2022. The hospital is an 800-beded facility catering to approximately 400,000 outpatients per year and about 68,000 inpatients per year in pre-COVID-19 period. The hospital is located in the state of Maharashtra which has recorded the maximum number of COVID-19 cases in the county.
Data for all patients admitted with COVID-19 were collected from electronic medical record database of the hospital. Patients with neurological manifestations secondary to COVID-19 occurring within 60 days of diagnosis of COVID-19 were included in the study. Patients seen in the outpatient department and those with pre-existing neurological diseases like dementia, Parkinson's disease, epilepsy who were admitted for treatment of COVID-19 were excluded. Self-reported isolated non-serious neurological symptoms like headache, fatigue, anosmia, loss of taste, myalgia, presyncope, and syncope were excluded. More than 250 patients with COVID-19-associated mucormycosis (CAM) were treated at out centre. We have excluded the patients with CAM from this study. Demographic details, neurological manifestations, underlying comorbidities, clinical presentation, laboratory results, maximum respiratory support required, other treatments, imaging, and outcomes were recorded. The incidence of neurological manifestations in COVID-19 was calculated based on the number of patients with neurological manifestations of COVID-19 divided by the total number of COVID-19 patients admitted. As the second wave of the pandemic started in India from Feb 11, 2021, and the third wave started approximately from Jan 1, 2022; cases seen before Feb 11, 2021 were considered to be part of the first wave; cases seen between Feb 11, 2021 to Dec 31, 2021 were part of the second wave while cases seen thereafter were considered in the third wave. The study was approved by the institute's ethics committee (Number IHR_2020_Aug_RK_378) and consent waiver was obtained.
A diagnosis of COVID-19 was made if the subject presented with clinical syndrome consistent with COVID-19 and had a positive SARS-CoV-2 polymerase chain reaction (PCR), rapid antigen test (RAT), COVID-19 antibody test or chest computerised tomography (CT) findings suggestive of COVID-19.
Encephalopathy was defined as disturbance in the level of awareness and attention secondarily leading to alteration in cognitive function, not primarily due to structural organic brain disease but because of altered metabolism, electrolyte disturbances, sepsis, toxins, or drugs. Encephalitis was defined as reduced level of consciousness with abnormal imaging or abnormal cerebrospinal fluid (CSF). Acute symptomatic seizure was defined as seizure with altered sensorium only during post-ictal phase lasting for a maximum duration of 48 hours without any deficits and normal neurological investigations. Other conditions were diagnosed as per their well-known definitions.
We described baseline characteristics as mean (+/-SD) or median (interquartile range) as appropriate for continuous variables and proportions for categorical variables. Continuous variables were compared using Student's t-test or Mann–Whittney U test as appropriate. Categorical variables were compared using Chi-square test or Fisher's exact test as appropriate. For all analysis, we considered two-sided P value <0.05 as statistically significant. All statistical analysis was performed using SPSS version 26 (SPSS for Windows, Chicago, SPSS Inc).
| Results|| |
There were 16,373 admissions with COVID-19 to the hospital from Mar 1, 2020 to Jan 31, 2022. Out of these, 1,551 patients required multiple hospital admissions for COVID-19; thus, a total of 14,822 patients with COVID-19 were admitted in the hospital. Out of these admissions, 8,440 were in the first wave, 5,855 were in the second wave and 527 in the third wave. Out of the 14,822 patients admitted with COIVD-19, 307 had neurological manifestations. Of these 307 patients, 22 (7.2%) were children while 285 (92.8%) were adults. The incidence of neurological manifestation in COVID-19 was 20.7 per 1,000 patients (2.07%). The baseline characteristics and neurological manifestations of these patients are described in [Table 1] and [Table 2], respectively.
There were 330 neurological manifestations among 307 patients. Some patients had >1 neurological manifestation. These included encephalopathy with critical illness neuromyopathy (CINM) in 5, acute ischemic stroke (AIS) with CINM in 4, encephalitis and CINM in 1, AIS with subarachnoid hemorrhage (SAH) in 1, AIS and encephalopathy in 2, intracerebral hemorrhage and SAH in 4, intracerebral hemorrhage and subdural hemorrhage (SDH) in 2, SAH and SDH in 1, myopathy and AIS in 1, transient ischemic attack (TIA) and encephalopathy in 1 and TIA and neuropathy in 1.
While comparing neurological manifestations in the three waves, 159/8,440 (1.87%) patients were seen in first wave; 139/5,855 (2.37%) had manifestations in second wave and 33/527 (6.26%) had manifestations in the third wave. Among the individual manifestations, encephalopathy (42.2% vs. 27.3% vs. 27.3%, P = 0.028) was more common in first wave; seizures were more common in the third wave, especially among children (5.1% vs. 5.7% vs. 39.3%, P = 0.001) and neuropathy was more common in the second wave (1.9% vs. 6.5% vs. 0%, P = 0.044). There was no statistically significant difference in other manifestations. To nullify the differences in the admission patterns in the three waves, we compared the individual neurological manifestations per 1000 COVID-19 admissions in each wave. By this method, encephalopathy, AIS and seizures were all more common in third wave. [Figure 1] shows the neurological manifestations in three waves per 1000 COVID-19 admissions.
|Figure 1: Neurological manifestations in the three waves of COVID-19 pandemic|
Click here to view
COVID-19 encephalopathy was the most common neurological manifestation seen in 114 (34.5%) patients. The detail characteristics of these are described in [Table 3]. We compared the risk factors among patients with COVID-19 encephalopathy who survived vs those who died. In patients having encephalopathy with COVID-19, hypoxia (p = 0.0001), shock (p = 0.001), renal involvement (p = 0.002), and sepsis (p = 0.033) were associated with higher mortality while those with no systemic involvement had better survival (p = 0.0001). There was increased mortality with increasing number of systemic comorbidities for encephalopathy (p = 0.0001) [Figure 2].
|Figure 2: Mortality with systemic comorbidities in COVID-19 encephalopathy|
Click here to view
A 49-year-old male with encephalopathy, myocarditis, and secondary bacterial infection. He developed seizures and left hemiparesis during hospital stay. MRI brain showed multiple areas of gyral thickening with diffusion restriction and post-contrast enhancement in bilateral fronto-parietal lobes with adjacent leptomeningeal enhancement [Figure 3]a. CSF analysis showed protein 26.4 mg/dl, glucose 60 mg/ml, and 2 cells. He was treated symptomatically and improved gradually. Another 27-year-old man presented with rapidly progressive illness with fever, acute renal dysfunction and worsening of sensorium. His CT brain showed bilateral thalamic and midbrain hypodensities [Figure 3]b. He succumbed to illness within two days.
|Figure 3: (a) MRI brain T2 FLAIR, DWI, T1W plain, and T1W contrast axial sequences showing multiple areas of gyral thickening with T2 FLAIR hyperintensities, diffusion restriction and post contrast enhancement in the bilateral fronto-parietal lobes suggestive of encephalitis. (b) CT brain plain of a patient with COVID-19 encephalitis showing hypodensities in bilateral thalami and midbrain*. (*Reproduced with permission. Chapter: Encephalitis and meningitis in COVID-19; Kulkarni R, Pujari S. Sylaja PN, editor. Reviews in Neurology 2021: Covid-19 and Neurology. India: Wolters Kluwer (i) Pvt. Ltd; 2021.)|
Click here to view
Acute ischemic stroke (AIS)
AIS was the second most common manifestation seen in 106 (32.1%) patients. Among patients with stroke, common comorbidities were hypertension 56 (52.8%), diabetes 42 (39.6%), new onset diabetes 2 (1.9%), ischemic heart disease 15 (14.2%), old stroke/TIA 12 (11.3%), and atrial fibrillation 4 (3.8%). Thirty-four (32.1%) patients had no traditional vascular risk factors; while 27 (25.5%) had 1 risk factor; 27 (25.5%) had 2 risk factors; 15 (14.2%) had 3 risk factors; 2 (1.9%) had 4 risk factors and 1 (0.9%) had 5 risk factors. Majority of patients were treated with aspirin (N = 103, 97.2%), clopidogrel (N = 61, 57.5%), and statins (N = 82, 77.4%). Six patients were thrombolysed, and two underwent decompressive craniotomy.
We divided the COVID-19-associated AIS into those with known vascular risk factors and those without obvious risk factors. The comparison in these two groups is described in [Table 4]. Those with traditional vascular risk factors were about nine years older and required median six days longer hospital stay.
Transient ischemic attack (TIA)
Eleven patients presented with TIAs out of which one had 2 episodes of TIAs. Mean age was 68.36 +/- 9 years (range 45–80 years).
Intracerebral hemorrhage (ICH)
Eleven patients had ICH. Ten patients were receiving heparin; 9 on antiplatelets (8 on single antiplatelets, 1 on dual antiplatelet agent) and one was on rivaroxaban when they developed hemorrhage. Four patients had parenchymal hemorrhage with SDH; while 2 had parenchymal hemorrhage with SAH. Two survived while nine (81.8%) died.
Cerebral venous thrombosis (CVT)
Two patients had CVT. A 55-year-old male had headache followed by vision loss and a 21-year-old female had anemia and was taking oral contraceptive pills when she developed CVT. Both improved with anticoagulation.
Sub-arachnoid hemorrhage (SAH)
Eight patients had SAH. Three of these patients had underlying malignancies (carcinoma bladder, recurrent carcinoma breast, and carcinoma ovary). Seven patients were on heparin, six were on aspirin, three were on rivaroxaban, and one on clopidogrel. Computed tomography angiogram (CTA) was performed in one patient which was normal. In rest of the seven patients, CTA could not be done due to poor general condition, these patients later died.
Sub-dural hemorrhage (SDH)
SDH occurred in eight patients. All of them were taking aspirin, six were also on heparin while one each was on clopidogrel and rivaroxaban. One post-partum lady developed SDH while on extra-corporal membrane oxygenation for COVID-19 treatment and another lady had carcinoma of ovary. One patient had both SDH and SAH. None of the patients were operated. Four (50%) of the patients with SDH died.
Acute symptomatic seizures
Twenty-nine (20 children and 9 adults) presented with seizures. Thirteen children presented with simple febrile seizures, six had complex febrile seizures one had seizure without fever. Eleven of the febrile seizures presented during the third wave. Among adults, eight had generalized and one had focal seizures. Electroencephalogram (EEG) was done in one patient which was normal. MRI brain in the patient with focal seizures showed left temporal and left frontal granulomas.
A 43-year-old man developed myelopathic features with lower limbs hypertonia, brisk reflexes, extensor plantar reflex, distal proprioceptive loss, Lhermitte symptom, and bladder involvement. His spine MRI did not show any abnormality and CSF was non-conclusive. He was treated with steroids without significant recovery. Another 61-year-old man presented with bilateral lower limb paresthesias and weakness for four days. MRI spine and CSF analysis were normal. Electrophysiology was not performed. He was treated symptomatically and improved marginally.
Guillain-Barre syndrome (GBS)
Six patients had GBS (Males-5; Females-1). Mean age was 62 years (range 48–78 years). The median duration of onset of GBS after COVID-19 was 25 days (IQR 10.5–54 days). All had demyelinating pattern of neuropathy. CSF analysis of four showed albumin-cytological disassociation, one was normal and in one patient, CSF could not be done. Four patients were treated with intravenous immunoglobulin (IVIg), one received plasmapheresis and one patient succumbed to the disease prior to the initiation of treatment. Three patients survived, two died and one was lost to follow up.
Critical illness neuro-myopathy (CINM)
Fifteen patients developed CINM. Median duration of hospitalization was 30 days (IQR 20-53 days). Five of them had encephalopathy; three had ischemic stroke, and one had encephalitis after which all of these patients developed CINM.
Three patients had cranial neuropathies in the form of isolated glossopharyngeal palsy presenting with acute onset bulbar palsy, left abducens palsy, and right facial palsy. All three had good recovery.
Twelve patients developed other neuropathies. Four had brachial plexopathies; two had isolated ulnar neuropathies, one had bilateral peroneal neuropathy and unilateral peroneal neuropathy. One patient developed vasculitic mononeuritis multiplex that was unmasked by COIVD-19 infection. Three other patients had sensory neuropathies with distal paresthesia.
A 47-year-old lady with diabetes, and hypertension developed acute kidney injury requiring hemodialysis one month after onset of COVID-19. She developed proximal lower limb weakness in hospital. Creatinine kinase (CK) was 1095 IU/dl and electromyography (EMG) showed non-specific findings. Right quadriceps muscle biopsy showed polygonal myofibers with minimal variation in fiber size and peripherally placed nuclei. There were perivascular and interstitial lymphocytic infiltrates suggestive of inflammatory myositis [Figure 4]. She also developed right paresis due to a left thalamic infarct. She was treated with oral steroids and her lower limbs power started improving. She died two months after discharge due to her medical comorbidities.
|Figure 4: Haematoxylin and eosin-stained sections of transversely and longitudinally cut skeletal muscle fibres (a- 40X, b- 100X) show preserved muscle architecture. Myofibres are polygonal with peripherally placed nuclei. There is perivascular and interstitial lymphocytic inflammatory infiltrate. Findings are suggestive of inflammatory myositis|
Click here to view
| Discussion|| |
In this study, we found 2.07% of all COVID-19 hospitalized subjects to have neurological manifestations described in the form of syndromes. This is one of the few studies which has reported a variety of neurological manifestations of COVID-19 spanning over three waves from a single center in India. The exact incidence of neurological complications is difficult to determine because of the differences in which neurological conditions were defined, method of data collection, system of recording, and bias in notifying. The incidence also varies based on whether the hospital is a tertiary referral center or a primary care hospital.
Two global consortia; the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-Neuro-COVID) and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) have reported neurological manifestations in COVID-19 patients. The most prevalent neurological syndromes were acute encephalopathy (49%), coma (17%), stroke (6%) whereas meningitis/encephalitis was rare (0.5%).
During the early phase of the pandemic, since the precise neurological presentations from this novel virus were not known, manifestations were described mainly as symptoms such as headache, myalgia, anosmia and ageusia and altered mental status. With further research in to the tropism of the virus, underlying pathogenesis and mechanisms by which many of the neurological symptoms occur were understood. This improved understanding of COVID-19 led to describe COVID-19 associated neurological syndromes such as encephalopathy, encephalitis, strokes, peripheral neuropathy, and others. A study by Liotta et al. reported mostly non-serious manifestations like headache, dizziness, dysgeusia, and anomia in 42.8%. Severe neurological manifestations like strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were rare (0.2-1.4%).
It is clear from literature that the non-serious self-reported neurological symptoms are more common with COVID-19. These are seen with most viral infections, are non-specific and do not necessarily suggest nervous system involvement. We felt that including these non-serious manifestations under the domain of neurological features was not justified.
In India, delta and omicron variants were the main strains in the second and third waves respectively. Omicron is believed to be more infectious and less virulent. In a study from Kerala, stroke was the most common neurological manifestation during the second wave of the pandemic. We analyzed the cases seen during all three waves of the pandemic and noticed that encephalopathy was statistically more common in the first wave, peripheral neuropathy in the second wave and acute symptomatic seizures in the third wave. However, when individual neurological manifestations were compared per 1000 COVID-19 admissions, encephalopathy, ischemic strokes and seizures were all more common in the third wave. Third wave, driven by omicron variant, causes less virulent disease leading to fewer hospitalizations. However, among those who required hospitalization, the above three manifestations were found to be high. We have collected data of third wave for only one month which could have led to statistical bias.
Encephalopathy is one of the most common neurological manifestations of COVID-19, which is often multifactorial. In our series, systemic comorbidities associated with encephalopathy were hypoxia 50.9%, renal impairment 42.1%, shock 20.2%, hepatic failure 14.9%, sepsis 14%, and hyponatremia 8.8%. There are very few studies which have discussed the break-up of the causes of encephalopathy in COVID-19 patients. In our study, we have seen a strong association between mortality and the number of systemic risk factors for encephalopathy. Factors attributed to the pathogenesis of encephalopathy include metabolic impairment, hypoxia, electrolyte disturbances, sepsis, inflammation/cytokines storm, endothelial damage, recurrent seizures, and direct viral tropism.,,,
Encephalitis is an uncommon complication of COVID-19 seen in <0.3% patients with high mortality. SARS-CoV-2 is a neuro-invasive neurotropic virus which enters central nervous system either through systemic circulation or through cranial nerves. Due to its high affinity for angiotensin converting enzyme 2 (ACE2) receptors, it gets attached to the capillary endothelium and neurons producing its effect on CNS. Encephalitic illness can also be secondary to inflammatory phenomenon. Areas of the brain shown to be involved are thalami, brainstem, corpus callosum, medial temporal lobes, white matter and basal ganglia. One patient showed fronto-parietal lobar involvement whereas the other showed bilateral thalamic and cerebellar affection. Since neuroimaging and CSF analysis could not be performed in many patients with encephalopathy, some cases of encephalitis could have been misclassified as encephalopathy.
Acute Ischemic stroke (AIS)
AIS were reported with COVID-19 right from the onset of the pandemic. The first study from Wuhan about neurological manifestations among COVID-19 subjects also reported strokes. There are many studies reporting AIS with COVID-19 with incidence varying from 1–6.1%. Strokes can be the presenting features of COVID-19, occur during the course of illness or occur after respiratory symptoms have subsided. Stroke was the second most common neurological manifestation in our study. The association between stroke and COVID-19 may be incidental, triggered, or causative. In an Indian study, half of the patients had the common risk factors including hypertension, diabetes mellitus or both. In our study, up to 33% of subjects presenting with stroke did not have any traditional vascular risk factors for stroke, suggesting that COVID-19 itself may have been causative. We observed that these patients were younger and required shorter hospital stay. The likely pathophysiological mechanisms for ischemic stroke are pro-thrombotic state during COVID-19, endothelial inflammation, cytokines released during infection, vasculitis due to infection, sepsis, myocardial injury predisposing patients to cardio-embolism and shock.,,,,, There were no differences in laboratory parameters in patients with or without traditional stroke risk factors.
In another smaller study, we had observed that about a third strokes had occurred while patients were taking antiplatelets/anticoagulation medications. Treatment protocols for COVID-19-associated AIS as well as its prevention are yet to be established.
Garcia et al. reported CVT in 3/826 (0.29%) patients, whereas our incidence of CVT was 0.01% (2/14,822). The same factors discussed as responsible for AIS are also likely to contribute to the development of CVT.
In our study, 27 (0.18%) patients had hemorrhages of which 8 had SDH, 11 had ICH, and 8 had SAH. In another study, 11 (1.05%) patients suffered hemorrhagic stroke of which 8 had ICH and 2 suffered SAH. In our study, hypertension was an important co-morbidity in 51.8% patients which could have been a strong etiological factor in the pathogenesis of hemorrhagic strokes. Hemorrhage carried a higher mortality (74%). Additionally, all patients with hemorrhage had received antiplatelet/anticoagulant therapy as a treatment of COVID-19. Since thromboembolic events are much more common and are an important cause of mortality in COVID-19, antiplatelet and/or anticoagulant agents are used to prevent these. Unfortunately, a small proportion of these patients suffer hemorrhagic strokes. Further studies are required to identify subset of patients who are at high risk of hemorrhages so that we can avoid using antiplatelet agents/anticoagulants in this subgroup.
Acute symptomatic seizure
Seizures can occur in COVID-19 as febrile seizures, acute symptomatic seizures; or secondary to encephalitis, encephalopathy and cerebrovascular events. The incidence of seizures reported in literature varies from 0.3-6.7%., We had 29 patients with acute symptomatic seizures of which 69% were children. We observed particularly higher incidence of seizures in the third wave driven by the omicron variant. This variant is known to present with seizures particularly in children.
We saw 36 (0.24%) patients were various neuropathies. Garcia et al. had reported neuropathy in 5.4% while Khedr et al. reported 3/439 patients having neuropathy other than GBS. The pathogenesis of neuropathy has been speculated to be immune mechanisms or direct neurotropic effects of the virus.,
Anosmia and ageusia can be considered as commonest cranial nerves involved in COVID-19. Other cranial nerves are involved in isolation or as part of GBS. Cranial neuropathies reported are unilateral or bilateral facial palsy followed by ocular motor and lower cranial nerve involvement. We encountered three patients, one each with isolated abducens, facial, and glossopharyngeal nerve palsy.
There were 15 cases of CINM in our series. Nine patients also had other neurological manifestations before development of CINM, emphasizing the fact that repeated careful neurological evaluation in critically ill patients for diagnosis of CINM. In a series of eight patients with COVID-19-associated CINM, critical illness neuropathy (CIN) was commoner than critical illness myopathy (CIM); whereas in non-COVID-19 patients who show more prevalence of CIM.
The reported incidence of GBS has been 0.67%, 0.05%, and 0.91% in Italian, Philippine, and Egyptian studies, respectively.,, From Western India, a large case series of 42 COVID-19 associated GBS cases found greater number of para-infectious GBS (61.9%) than post infectious GBS (38%). We reported six patients with GBS (0.04%) with mean onset of GBS 25 days after COVID-19; where all patients had demyelinating pattern.
Though myalgias are common in COVID-19, myositis is rare., Our patient with myositis had biopsy proven inflammatory myopathy and had shown improvement with steroids. Further research is needed to determine the pathogenesis of myositis in COIVD-19.
Due to the highly infectious nature of COVID-19, detailed examination and investigations like CSF analysis, MRI brain were not possible in all patients admitted with COVID-19.
The incidence of neurological manifestations in COVID-19 was calculated from patients with neurological manifestations due to COVID-19 who were admitted in our hospital. Hospital treated 14,822 COVID-19 patients and some of them might have developed neurological complications after discharge and sought treatment elsewhere. It was not possible to follow up the whole cohort of patients.
We have not been able to provide COVID-19 vaccination status and viral strain analysis for the patients.
| Conclusions|| |
SARS-CoV-2 produces myriad of neurological manifestations including central and peripheral nervous system involvement. The incidence of serious neurological manifestations was 2.07% among 14,822 COVID-19 inpatients. The neurological manifestations seen were encephalopathy, encephalitis, AIS, ICH, SAH, SDH, acute symptomatic seizures, non-compressive myelopathy, cranial and peripheral neuropathies and myositis. Encephalopathy was more common in first wave while childhood acute symptomatic seizures were more common in third wave. Encephalopathy was the commonest neurological manifestation with progressively higher mortality with increased number of systemic comorbidities. AIS was seen in patients who had traditional risk factors (67.9%) as well as in those without them (32.1%). Research needs to be undertaken to study the pathogenesis of neurological manifestations which may help us to improve the treatment of these complications and reduce mortality.
Mahesh Mandolkar, Department of Pathology, Deenanath Mangeshkar Hospital and Research Center, for providing slides for [Figure 4].
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al
. Neurologic manifestations of hospitalized patients with Coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.
Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, et al
. The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings. Brain 2020;143:3104-20.
Liotta EM, Batra A, Clark JR, Shlobin NA, Hoffman SC, Orban ZS, et al
. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann Clin Transl Neurol 2020;7:2221-30.
Chou SH, Beghi E, Helbok R, Moro E, Sampson J, Altamirano V, et al
. Global incidence of neurological manifestations among patients hospitalized with COVID-19-A report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open 2021;4:e2112131.
D V, Sharma A, Kumar A, Flora SJS. Neurological manifestations in COVID-19 patients: A meta-analysis. ACS Chem Neurosci 2021;12:2772-97.
Khedr EM, Abo-Elfetoh N, Deaf E, Hassan HM, Amin MT, Soliman RK, et al
. Surveillance study of acute neurological manifestations among 439 Egyptian patients with COVID-19 in Assiut and Aswan University Hospitals. Neuroepidemiology 2021;55:109-18.
Fogang YF, Noubom M, Bassong PY, Mbonda, PC, Mfopou IN, Gams DM, et al
. Neurological manifestations in patients with symptomatic COVID-19 admitted to the Bafoussam Regional Hospital, Cameroon. Pan Afr Med J 2021;38:326.
García S, Cuatepotzo-Burgos FM, Toledo-Lozano CG, Balderrama-Soto A, Alcaraz-Estrada SL, Montiel-López L, et al
. Neurological manifestations and outcomes in a retrospective cohort of Mexican inpatients with SARS-CoV-2 pneumonia: Design of a risk profile. Healthcare (Basel) 2021;9:1501.
George M, Baby N, Azad A, Rajan A, Radhakrishnan SK. Neurological disorders seen during second wave of SARS-CoV-2 pandemic from two tertiary care centers in central and Southern Kerala. Ann Indian Acad Neurol 2021;24:917-26. [Full text]
Travi G, Rossotti R, Merli M, D'Amico F, Chiappetta S, Giussani G, et al
. Neurological manifestations in patients hospitalized with COVID-19: A retrospective analysis from a large cohort in Northern Italy. Eur J Neurosci 2021;53:2912-22.
Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG; Philippine CORONA Study Group Investigators. COVID-19 outcomes of 10,881 patients: Retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study). J Neural Transm (Vienna) 2021;128:1687-703.
Yassin A, Nawaiseh M, Shaban A, Alsherbini K, El-Salem K, Soudah O, et al
. Neurological manifestations and complications of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. BMC Neurol 2021;21:138.
Nepal G, Rehrig JH, Shrestha GS, Shing YK, Yadav JK, Ojha R, et al
. Neurological manifestations of COVID-19: A systematic review. Crit Care 2020;24:421.
Yang W, Shaman J. COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant, and implications for vaccination. medRxiv 2021:2021.06.21.21259268. doi: 10.1101/2021.06.21.21259268.
Singhal T. The emergence of Omicron: Challenging times are here again! Indian J Pediatr 2022:1-7. doi: 10.1007/s12098-022-04077-4.
Kulkarni R, Pujari S, Gupta D, Advani S, Soni A, Duberkar D, et al
. RhinoOrbitoCerebral mycosis and COVID19: From bad to worse? Ann Indian Acad Neurol 2022;25:68-75. [Full text]
Kodge BG. A review on current status of COVID19 cases in Maharashtra state of India using GIS: A case study. Spat Inf Res 2021;29:223-9.
Ranjan R, Sharma A, Verma MK. Characterization of the second wave of COVID-19 in India. medRxiv 2021. doi: 10.1101/2021.04.17.21255665.
Uginet M, Breville G, Assal F, Lövblad KO, Vargas MI, Pugin J, et al
. COVID-19 encephalopathy: Clinical and neurobiological features. J Med Virol 2021;93:4374-81.
Siow I, Lee KS, Zhang JJY, Saffari SE, Ng A. Encephalitis as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes, and predictors. Eur J Neurol 2021;28:3491-502.
Iuliano AD, Brunkard JM, Boehmer TK, Peterson E, Adjei S, Binder AM, et al
. Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-CoV-2 high transmission periods-United States, December 2020-January 2022. MMWR Morb Mortal Wkly Rep 2022;71:146-52.
Kulkarni R, Pujari SS. Meningitis and encephalitis in COVID-19. In: Sylaja PN, editor. Reviews in Neurology 2021: Covid-19 and Neurology. India: Wolters Kluwer (I) Pvt. Ltd; 2021. p. 167-73.
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al
. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020;382:e60.
Bhatia R, Srivastava MVP. COVID-19 and stroke: Incidental, triggered or causative. Ann Indian Acad Neurol 2020;23:318-24. [Full text]
Benny R, Singh RK, Venkitachalam A, Lalla RS, Pandit RA, Panchal KC, et al
. Characteristics and outcomes of 100 consecutive patients with acute stroke and COVID-19. J Neurol Sci 2021;423:117348.
Kulkarni R, Pujari S, Palasdeokar N, Jagtap S, Jog S, Khan ZA. COVID-19 and acute ischemic stroke; An Indian experience. Ann Indian Acad Neurol 2021;24:632-4. [Full text]
Ludvigsson JF. Convulsions in children with COVID-19 during the Omicron wave. Acta Paediatr 2022. doi: 10.1111/apa. 16276.
Finsterer J, Scorza FA, Scorza C, Fiorini A. COVID-19 associated cranial nerve neuropathy: A systematic review. Bosn J Basic Med Sci 2022;22:39-45.
Bocci T, Campiglio L, Zardoni M, Botta S, Coppola S, Groppo E, et al
. Critical illness neuropathy in severe COVID-19: A case series. Neurol Sci 2021;42:4893-8.
Dhamne MC, Benny R, Singh R, Pande A, Agarwal P, Wagh S, et al
. Guillian--Barre' syndrome in patients with SARS-CoV-2: A multicentric study from Maharashtra, India. Ann Indian Acad Neurol 2021;24:339-46. [Full text]
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]