COVID-19 primarily affects respiratory system, however, it can affect other systems too, including nervous system. This presentation offers details about neurological symptoms and disorders seen in patients with COVID-19.

1. Neurological Manifestations of COVID-19 Infection
Dr. Sudhir Kumar MD DM
Senior Consultant Neurologist
Apollo Hospitals, Hyderabad

2. Introduction
• The novel severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2) emerged in Wuhan, China and rapidly spread worldwide
• Vast majority of confirmed cases present with respiratory symptoms.
• Neurological manifestations: Case reports, case series, editorials,
reviews, case-control and cohort studies
• The discrimination between causal relationship and incidental
comorbidity is often difficult

3. Neurological manifestations of coronavirus infections
• Upon nasal infection, coronavirus enters the central nervous system (CNS)
through the olfactory bulb causing inflammation and demyelination.
• The virus can reach the whole brain and cerebrospinal fluid (CSF) in less than
seven days.
• The central and peripheral nervous system involvement may be related to hypoxia
and endothelial damage, uncontrollable immune reaction and inflammation,
electrolyte imbalance, hypercoagulable state, DIC, septic shock and/or multiple
organ failure.
European Journal of Epilepsy 79 (2020) 49–52

4. Brian Fiani, et al 2020
Pathophysiology

5. Neurological complications of COVID 19
Rachel Bridwell et al 2020

6. Symptoms

7. Common Neurological Manifestations of COVID-19 (%)
Critical Care, 2020

8. Neurological
manifestations
timeline
Approximate timeline for COVID-19-associated neurological disease:
ADEM=acute disseminated encephalomyelitis. SARS-CoV-2=severe acute respiratory syndrome coronoavirus 2.
Lancet Neurol. 2020;S1474-4422(20)30221-0

9. Stroke and COVID19
Acute stroke may complicate or co-exist with COVID-19;
5%, acute ischemic stroke
0.5% cerebral venous sinus thrombosis
and 0.5% of the patients developed cerebral haemorrhage
Li Y, Wang M, Zhou Y, et al. Acute cerebrovascular disease following COVID-19: a
single center, retrospective, observational study,
https://papers.ssrn.com/sol3/papers.cfm?abstract_ id=3550025 (2020, accessed 4 April 2020).

11. (A) Hyperintensity along the wall of inferior horn of right lateral
ventricle on diffusion-weighted imaging, indicating ventriculitis.
(B) Hyperintense signal changes in the right mesial temporal lobe
and hippocampus with slight hippocampal atrophy on FLAIR MRI,
consistent with encephalitis, in a patient with COVID-19.
(C) Hyperintensity within the bilateral medial temporal lobes and
thalami on T2/FLAIR MRI.
(D) Evidence of hemorrhage, indicated by hypointense signal on
susceptibility-weighted images, consistent with acute necrotizing
encephalopathy in a patient with confirmed COVID-19.
(E) CT showing ischemic lesions involving the left occipital lobe.
(F) Right frontal precentral gyrus of the brain in a man aged 64 years
who deteriorated neurologically after admission to hospital with
COVID-19 and was diagnosed with acute stroke.
Brain imaging in patients with neurological disease associated with COVID-19
Lancet Neurol. 2020;S1474-4422(20)30221-0

12. COVID-19 and Guillain-Barre Syndrome
• GBS can occur following COVID-19 infection,
• 5-10 days after the symptom onset of COVID-19,
• Ascending type, LL>UL, with paresthesia and facial weakness
• Axonal or demyelinating type,
• CSF- mild pleocytosis, mildly raised protein
• Treatment- with IVIG/plasma exchange.
• Outcome- is generally good.

13. COVID-19 and Loss of Smell & Taste
• Loss of smell and taste are reported in 55-60% of patients,
• They can occur before (12%), along with (23%) or after the onset
(65%)of typical COVID symptoms,
• These abnormalities persist in >60% even after resolution of typical
COVID symptoms,

14. COVID-19 and BELL’S PALSY
• 65-year old lady in China
• LMN type of facial palsy, without any fever or respiratory symptoms,
• RT-PCR on throat swab positive, and CT showed ground-glass
opacities in right lower lung,
• Resolved with antiviral treatment

15. Are PWE at higher risk of developing COVID-19?
• PWE are not at an increased risk of getting COVID-19
• Epilepsy does not increase the severity of COVID-19

16. SARS and seizures
In a more recent study:
 Among 183 hospitalized children with clinically suspected acute encephalitis, 22 (12%) had coronavirus
infection by detection of anti-CoV IgM.
 Five of these 22 patients (23%) had seizures.
 Cerebrospinal fluid was analysed in all patients with coronavirus-associated encephalitis; 10 patients
(45.5%) had CSF pleocytosis.
 Three of the 22 patients with corona virus associated encephalitis underwent electroencephalography
(EEG); all three results were normal.
• SeizureSARS: severe acute respiratory syndrome, CSF: cerebrospinal fluid, CoV IgM: corona immunoglobulin M Seizure; European Journal of Epilepsy 79

17. COVID-19 and
seizures
Seizure, European Journal of Epilepsy 79 (2020) 49–52

18. COVID-19 and seizures contd..
• A growing body of evidence shows that neurotropism is one common feature of coronaviruses.
• Neurological manifestations of COVID-19 could document CNS manifestations in 25% of the patients [headache (13%),
dizziness (17%), impaired consciousness (8%), acute cerebrovascular problems (3%), ataxia (0.5), and seizures (0.5%)].
• Meningitis/encephalitis associated with SARS-CoV2 accompanied by seizures (SARS-CoV2 RNA was detected in the
CSF).
• In patient affected by COVID-the primary presentation was a focal status epilepticus.
• COVID-19 patients develop seizures as a consequence of hypoxia, metabolic derangements, organ failure, or even
cerebral damage
CNS: Central nervous system, RNA: ribo-nucleic acid, SARS-
CoV2: severe acute respiratory syndrome-coronal virus
Seizure, European Journal of Epilepsy 79
(2020) 49–52

19. Management of seizures
• In critically ill patients, untreated seizures can quickly escalate to generalized convulsive status
epilepticus or, more frequently, nonconvulsive status epilepticus (NCSE).
• If a patient with COVID19 develops a clinical or subclinical seizure or status epilepticus, it is very
reasonable to start the treatment with antiseizure medication(ASM) urgently.
• Determine the cause of the seizure and manage the cause [e.g., hypoxia, fever (in children),
metabolic derangements, etc.] immediately.
• When an ASM is initiated, drug factors, such as the onset of action, drug interactions, and adverse
effects, and also patient factors (age, respiratory, renal, hepatic, and cardiac functions) should be
taken into account.
ASM: Anti-seizure medication
Seizure: European Journal of Epilepsy 79
(2020) 49–52

20. Different scenarios of seizure management in critically ill
patients with COVID-19
A single seizure less than 5min long:
 Because these patients suffer from severe respiratory and/or cardiac problems, drugs with
significant respiratory/cardiac adverse effects (e.g., Phenytoin, Phenobarbital, etc.) should be
prescribed cautiously.
 Drugs with significant drug interactions (e.g., Carbamazepine, Phenytoin, Phenobarbital, and
Valproic acid) should be prescribed cautiously
 Lacosamide should be used with caution in patients with cardiac conduction problems (e.g.,
marked first-degree AV block, second-degree or higher AV block),
 Brivaracetam is a safe treatment option in these patients.
 Similarly, levetiracetam is an optimal ASM in critically ill patients with a reasonable adverse effect
profile and minimal interactions with other drugs
ASM: Anti-seizure medication Seizure, European Journal of Epilepsy 79 (2020)
49–52

21. Anti-seizure medications potentials for interactions with
other drugs
Neurol Sci. 2020 Jun 27;1-7.

22. Different scenarios of seizure management in critically ill
patients with COVID-19 contd..
More than one seizures (either shorter or longer than 5min) or status epilepticus
(convulsive or nonconvulsive):
 General management principals of serial seizures and status epilepticus should be applied.
 New-onset seizures in these patients could be considered as acute symptomatic seizures.
 Patients with acute symptomatic seizures do not need long-term ASM therapy after the period of acute
illness, unless a subsequent seizure occurs.
 Since the period from the onset of COVID-19 symptoms to death may range from 6 to 41 days, it is reasonable
to continue the ASM for about 6 weeks and then tapper and discontinue the drug rapidly in 1–2 weeks.
ASM: Anti-seizure medication European Journal of Epilepsy 79 (2020) 49–52

23. COVID-19 in people with epilepsy: An altered management approach
• The International League Against Epilepsy (ILAE) has provided valuable resources to tackle some of the
important issues on this topic.
• Drug-drug interactions between ASMs and anti-COVID therapies may pose significant challenges.
• Furthermore, cardiac, hepatic or renal impairments, which may happen in patients with severe COVID-19,
may require adjustment to ASMs.
• Adverse effects of both groups of therapies (ASMs and anti-COVID therapies) should be considered.
• Administering hydroxychloroquine to a patient with epilepsy, who is already taking Lacosamide, may carry an
added risk and should be done with precaution and ECG monitoring.
• Also, QT prolongations may occur with azithromycin and chloroquine and some ASMs (e.g., Carbamazepine,
Lacosamide, Phenytoin, and Rufinamide) may cause cardiac conduction abnormalities.
ASM: Anti-seizure medication European Journal of Epilepsy 79 (2020) 49–52

24. Clinically relevant DDI between AEDs and medications used in the
treatment of COVID-19 patients
DDI, drug-drug interaction; ATV, atazanavir; DRV/c, darunavir/cobicistat LPV/r, lopinavir/ritonavir; RDV, remdesivir/GS-5734;
FAVI, favipiravir; CLQ, chloroquine; HCLQ, hydroxychloroquine; NITA, nitazoxanide; RBV, ribavirin; TCZ, tocilizumab; IFN-β-
1a; interferon β-1a; OSV, oseltamivir https://www.ilae.org/files/dmfile/Antiepileptic-drugs-interactions_in_COVID-19.pdf

25. Issues with access to ASMs during the COVID-19
pandemic and utility of telemedicine
 SARS outbreak in 2003 in Taiwan, showed that 22% of the people did not receive their medications; 12% of
the patients suffered seizure worsening during the outbreak.
 In the context of a pandemic, telemedicine, particularly video consultations, should be promoted and scaled up.
 Should have a regulatory framework to authorize, integrate, and reimburse telemedicine services.
 In the COVID-19 pandemic, integrated telemedicine in national healthcare system, is a call to adopt.
ASM: Anti-seizure medication European Journal of Epilepsy 79 (2020) 49–52

26. Summary
• Neurologic findings vary from non-specific to specific symptoms in
COVID-19 patients.
• Some severe symptoms or diseases can present in the later stage of the
disease.
• Should be aware of the presence of neurologic signs & symptoms as a
chief complaint of COVID-19

27. References
[1] Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020;26(Febuary):102433https://doi. org/10.1016/j.jaut.2020.102433.
[Epub ahead of print].
[2] Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci 2018;12:386.
[3] Hung Ec, Chim Ss, Chan Pk, Tong Yk, Ng Ek, Chiu Rw, et al. Detection of SARS coronavirusRNAinthecerebrospinal fluidofapatientwithsevereacuterespiratory syndrome. Clin Chem
2003;49:2108–9.
[4] Lau KK, Yu WC Chu CM, Lau ST, Sheng B, Yuen KY. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis 2004;10:342–4.
[5] Li Y, Li H, Fan R, Wen B, Zhang J, Cao X, et al. Coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children. Intervirology
2016;59:163–9.
[6] Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection:asingle-
centerexperienceinSaudiArabia.IntJInfectDis2014;29:301–6.
[7] Algahtani H, Subahi A, Shirah B. Neurological complications of middle east respiratory syndrome coronavirus: a report of two cases and review of the literature. Case Rep Neurol Med
2016;2016:3502683.
[8] Dominguez SR, Robinson CC, Holmes KV. Detection of four human coronaviruses in respiratory infections in children: a one-year study in Colorado. J Med Virol 2009;81:1597–604.
[9] Carman KB, Calik M, Karal Y, Isikay S, Kocak O, Ozcelik A, et al. Viral etiological causes of febrile seizures for respiratory pathogens (EFES Study). Hum Vaccin Immunother 2019;15:496–502.
[10] Woo PC, Yuen KY, Lau SK. Epidemiology of coronavirus-associated respiratory tract infections and the role of rapid diagnostic tests: a prospective study. Hong Kong Med J 2012;18(Suppl
2):22–4.
[11] Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J Med Virol 2020;27(Febuary).
https://doi.org/10.1002/jmv.25728. [Epub ahead of print].
[12] Mao L, Wang M, Chen S, et al. Neurological Manifestations of hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol 2020;10(April):e201127.
[13] MoriguchiT,HariiN,GotoJ,etal.A firstcaseofMeningitis/Encephalitisassociated with SARS-Coronavirus-2. Int J Infect Dis 2020(20 April):30195–8. https://doi.org/ 10.1016/j.ijid.2020.03.062.
[Epub ahead of print]. 3. pii: S1201-S9712.