Headache Medicine 2021, 12(4):338-342 p-ISSN 2178-7468, e-ISSN 2763-6178

338

ASAA

DOI: 10.48208/HeadacheMed.2021.57

Headache Medicine

Case report

Encephalitis associated with Covid-19 and thunderclap headache:

an unusual relationship

Emanuelle Bianchi da Silva Rocha , Camila Moraes Eberhardt , Luciana de Azevedo Tubero ,

Letícia Araújo Tassini Penatti , Andressa Regina de Mello Galego

Faculdade de Medicina de São José do Rio Preto (FAMERP), São Paulo, Brazil

Abstract

The Covid-19 is characterized mainly by respiratory symptoms, however this virus

frequently damages the nervous system, although the exact mechanism involved is still

unclear. Headache is the most common neurological symptom and has a great hete-

rogeneity, including thunderclap headache which should be considered a red ag on

emergency departments.

Objectives

The case of a 51 years-old woman with thunderclap headache started seven days be-

fore, which progressed with mental confusion, inattention and language plus memory

disturbance on the day of admission, is reported. General physical examination was

normal except for the presence of borderline pyrexia (37.7 °C). Neurological examination

showed no particularities, except for mental and cognitive alterations. Computed angio-

tomography of the brain excluded bleeding but showed one aneurysm. Cerebrospinal

uid (CSF) had no xanthochromia, but evidenced a lymphomonocytic pleocytosis with

discrete hyperproteinorraquia. Due to hospital protocol the patient underwent computed

tomography of thorax and we found ground-glass opacities suggesting viral infection.

Then, RT-PCR for Sars-CoV-2 with nasopharyngeal swab and in CSF was performed with

both positives. Therefore, the diagnosis was encephalitis associated with Covid-19. We

opted for supportive care only. Patient evolved with many complications, need of ventila-

tory support and renal replacement therapy, but she was discharged after 35 days with no

symptoms and at follow-up, two months later, the only nding was mild inattention.

Emanuelle Bianchi da Silva Rocha

m.bianchis@hotmail.com

Edited by:

Marcelo Moraes Valença

Keywords:

Covid-19

Sars-CoV-2

Headache

Encephalitis

Thunderclap headache

Hemorrhagic subarachnoid

Received: March 3, 2022

Accepted: March 18, 2022

339

ASAA

Rocha EBS, Eberhardt CM, Tubero LA, Penatti LAT, Galego ARM

Encephalitis associated with Covid-19 and thunderclap headache: an unusual relationship

Introduction

he disease caused by the novel coronavirus is classical-

ly characterized by the involvement of the respiratory

system however it has a wide spectrum of manifestations,

including damage to the nervous system (NS). Retrospective

study developed in Wuhan in 2019 with 214 patients, still

at the beginning of the pandemic, showed a prevalence

of neurologic manifestations of 37%.

The most common

neurological symptom reported was headache, with differ-

ent characteristics and great heterogeneity among those

affected.

Thunderclap headache, as the name says, is a sudden

severe pain usually caused by potentially serious disorders,

mainly vascular disturbances, therefore it consists of a

medical emergency, especially when associated with

altered mental state.

In a recent study with 262 patients

with Covid-19 and headache around 25% presented

severe or very severe pain.

Another publication with

2,194 participants evidenced that red ags for headache

were present in 61% of the cases, but confusion was the

warning sign only in 6.2% and sudden onset just in 5.8%.

Here we report a case of a patient admitted at a hospital

reference in neurology with a suspect of hemorrhagic stroke

with a history of thunderclap headache plus altered mental

state without systemic symptoms and after investigation,

surprisingly, diagnosed with encephalitis associated with

Sars-CoV-2.

Case Report

Woman, 51 years-old, previous history positive just for

depression and systemic arterial hypertension, non-

smoker. Admitted at hospital reference to neurology

withsuspicion of hemorrhagic stroke, reporting seven days

of holocranial and sudden headache that has progressed

to severe intensity within minutes at onset. Associated with

evolution to mental confusion, inattention, inability to meet

family members and difculty of communicating at the day

of admission.

Admitted normotensive (130/70 mmHg), normocardic (96

bpm), saturating 97% without oxygen supplementation,

without respiratory distress and with a borderline pyrexia

of 37.7°C. General physical examination, including

respiratory auscultation, was normal. In the neurological

examination of admission, the patient was inattentive,

hypocontactant, drowsy but awake with verbal stimulus,

disoriented in time and space, unable to say her own

name or recognize her husband and with a language

disturbance, characterized by relative uent speech,

incapacity to name objects, repeat words or phrases and

to obey commands. The muscular thonus was normal and

the patient moved the four members without fall in decit

maneuvers. She had no signals of pyramidal liberation

or any other alteration at neurological examination,

including absence of neck stiffness.

General laboratory tests were normal. Brain and neck

computed angiotomography (CTA) excluded acute

bleeding, however showed one saccular aneurysm with

1.2 x 0.9 millimeters in the supraclinoid/paraophthalmic

segment of the left internal carotid artery (Figure 1).

We performed cerebrospinal uid (CSF) mainly with the

objective to rule out subarachnoid hemorrhage (SAH)

and the liquid was clear without xanthochromia, but

with slight lymphomonocytic pleocytosis (8 leukocytes),

discrete protein elevation (53 mg/dL) and 34 red blood

cells. Electroencephalogram (EEG) showed symmetrical

and disorganized brain electrical activity with poor

anteroposterior differentiation, theta rhythm diffuse

and presence of triphasic waves, suggestive of an

encephalopathy.

Due to the hospital protocol during the Covid-19 pandemic,

the patient underwent computed tomography of the thorax

and we found ground-glass opacities involving around

25% to 50% of the lungs, predominantly at peripheral

regions, suggesting viral infection (Figure 2). Therefore,

RT-PCR for Sars-CoV-2 with nasopharyngeal swab was

performed with a positive result. Family members denied

respiratory complaints or any other symptoms and denied

contacts prior to the admission with conrmed or suspected

cases of coronavirus disease. The patient had not traveled

recently. The patient did not perform magnetic resonance

imaging due to the institution’s isolation rules for cases of

coronavirus disease.

After that, added to the exclusion of hemorrhagic stroke

and SAH, our suspicion was viral encephalitis. We started

empirical treatment with acyclovir and solicited sorologies

at cerebrospinal uid for herpes simplex virus and for

Sars-CoV-2. The rst result was negative, so the acyclovir

was suspended and the last result was positive, conrming

the diagnosis of Covid-19 encephalitis.

We opted to maintain just supportive care, without

immunosuppressive treatments. During hospitalization, the

340

ASAA

Rocha EBS, Eberhardt CM, Tubero LA, Penatti LAT, Galego ARM

Encephalitis associated with Covid-19 and thunderclap headache: an unusual relationship

neurosurgery team evaluated her because of the aneurysm

visualized on CTA and they opted for conservative

treatment. The level of consciousness of the patient worsened

progressively and she developed an aspiration pneumonia,

requiring orotracheal intubation. At the intensive care unit

(ICU), even under the inuence of sedatives, the patient

presented diffuse myoclonus, pyramidal signs and spasticity

diffuse, suggesting seizure and managed with phenytoin

and dose adjustment of sedatives. A new EEG evidenced

occasional epileptiform disorders in the left temporal region

with one electrographic seizure, but without alterations

compatible with status epilepticus.

For 30 days, she remained at ICU, requiring multiple cycles

of broad-spectrum antibiotics and renal replacement

therapy, progressing to the need for tracheostomy with

subsequent decannulation. She was discharged from

hospital 35 days after admission, alert, with no language

or memory disturbance, oriented in time and space. On

follow-up, two months later, the patient presented just mild

inattention, without impact on their usual activities.

Comments

Headache is a common complaint in emergency

departments/hospitals and one of the scariest etiologies

is SAH, with rates of mortality of up to 65% and

misdiagnosis of up to 51%.

Almost 70% of these cases

Figure 1. A: Head computed angiotomography - precontrast phase without acute bleeding; B: Head angiotomography -

axial section evidencing a saccular aneurysm with 1.2 x 0.9 millimeters in the supraclinoid/paraophthalmic segment of

the left internal carotid artery; C: Head angiotomography - coronal section evidencing the aneurysm described above;

D: Head angiotomography - sagittal section evidencing the aneurysm described above.

341

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Rocha EBS, Eberhardt CM, Tubero LA, Penatti LAT, Galego ARM

Encephalitis associated with Covid-19 and thunderclap headache: an unusual relationship

will present headache as the rst symptom and, although

not well described in literature, around 50% of the patients

will experience the thunderclap headache.

Considering

all of the above, faced with a case as we describe here,

with thunderclap headache and neurological ndings,

investigating SAH is mandatory.

The rst step in the investigation is the head computed

tomography (CT).

Usually CTA is performed after

conrmed SAH for screening of aneurysms (the most

common cause of SAH) and/or program the therapeutic

or when the diagnosis is still a doubt.

5,6

In our case, we performed the CTA rst because in our

institution this exam can be realized as fast as the CT

without delaying the diagnosis and has a high sensitivity to

detect aneurysms.

This exam in our patient did not detect

bleeding, but identied one aneurysm. After three days of

the symptoms onset the sensitivity of CT starts to decrease

and almost half is negative for SAH after seven days, often

necessitating a lumbar puncture (LP) and the presence of

xanthochromia in the CSF is suggestive of SAH because of

heme metabolism.

5,6

Considering the symptoms reported

on admission, the time of evolution and the detection of

aneurysm on CTA we proceeded to the next step and

performed a LP that did not show xanthochromia. CSH is

also useful for differential diagnostics and in our case was

the key point.

According to the literature, infection can be the cause

behind a thunderclap headache.

The pathophysiological

mechanism involved in the neurological manifestations of

SARS-CoV-2 is still unclear, but invasion of the NS can

occur by transsynaptic transport or by hematogenous

dissemination, in addition, this virus can lead to an

exacerbated immune response that damages NS.

Recent review with 2,194 cases of Covid-19 identied

a prevalence of headache of 30%, however just around

6% had this as the rst symptom and more than 90% had

systemic symptoms.

Red ags around headache were

present in 264 participants but as we described at the

introduction, altered mental state and sudden onset occurred

in a few cases.

Contrasting with that here we present a

case characterized by intense and sudden headache that

evolved for altered mental state without systemic symptoms

and without any suggestion of respiratory infection, except

by the presence of borderline pyrexia.

Figure 2. Computed tomography of thorax evidencing ground-glass opacities and sparse bilateral foci of consolidation, predominantly in the

peripheral with pulmonary involvement around 25-50%.

342

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Rocha EBS, Eberhardt CM, Tubero LA, Penatti LAT, Galego ARM

Encephalitis associated with Covid-19 and thunderclap headache: an unusual relationship

Encephalitis associated with Sars-CoV-2 is a rare

neurological manifestation and altered level of

consciousness and/or mental state, seizures, headache

and weakness are the most frequent presentations.

7-9

accordance with the literature, our patient had almost all

these symptoms. The detection of the virus at the CSF is

very uncommon

7,8

, in contrast to that the RT-PCR for Sars-

CoV-2 of our patient was positive.

Patients with Covid-19 and encephalitis have a poor

prognosis compared to others affected by such virus

and,

unfortunately, until now we do not have a standardized

treatment.

8,9

Here we report a case that presented serious

complications, but had an excellent recovery, even without

immunosuppressive treatments.

In conclusion, the authors want to point out that headache

is a common symptom in the emergency departments in

patients with Covid-19 or not. It can be the rst signal of

the novel coronavirus infection or of a complication of that,

like encephalitis. In addition, the pain has a very range of

phenotypes including thunderclap headache mimicking an

SAH, as we approach here. Therefore, in the context of a

contagious pandemic disease health professionals have to

be prepared for the prompt recognition of this infection.

Contribution’s of authors: EBSR, CME, LAT and LATP,

acquisition of data conception of the work, drafting the

work; ARMG, interpretation of data, revising intellectual

content, approval of the nal version and agreement to

be accountable for all aspects of the work in ensuring that

questions related to the accuracy or integrity of any part

of the work are appropriately investigated and resolved.

Conflict of interest: the authors deny any conict of interest.

Funding: no support funding

Emanuelle Bianchi da Silva Rocha

https://orcid.org/0000-0003-4801-8931

Camila Moraes Eberhardt

https://orcid.org/0000-0001-8720-9533

Luciana de Azevedo Tubero

https://orcid.org/0000-0001-6698-993X

Letícia Araújo Tassini Penatti

https://orcid.org/0000-0002-1129-2702

Andressa Regina de Mello Galego

https://orcid.org/0000-0003-1609-3486

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