Headache Medicine 2021, 12(2) p-ISSN 2178-7468, e-ISSN 2763-6178

141

ASAA

DOI: 10.48208/HeadacheMed.2021.25

Headache Medicine

Case Report

Cluster headache due to intranasal herpes simplex: a case report

Leonardo de Sousa Bernardes

, Renan Domingues Oliveira

, Mário Fernando Prieto Peres

Neurology Department, Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil

Neurology Department, Hospital Israelita Albert Einstein, São Paulo, Brazil

Abstract

Cluster headache is characterized by pain in the trigeminal nerve's rst division and au-

tonomic features, with attacks lasting from 15 minutes to 180 minutes, up to eight times a

day. Although considered a primary headache, it may be mimicked by structural diseases

like infections, inammation, tumor, and vascular. Intranasal and sinus infectious were also

reported. Herpes simplex infections are quite common in the general population, and the

nerve ganglia are the natural reservoir of the virus. Intranasal herpes, on the other hand,

is exceedingly rare, with only a few cases reported in the literature. Our main objective is

to describe a case report of a 49-year-old man who was diagnosed with intranasal herpes

infection during a bout of cluster headache, evaluated by an otolaryngologist. He got free

of symptoms after using valacyclovir and melatonin. Thus, herpes simplex might be involved

in the mechanisms of secondary or primary cluster headache. Further research is necessary

to help elucidate this relationship.

Leonardo de Sousa Bernardes

Santa Casa de Misericórdia de

São Paulo

leosb@hotmail.ca

Edited by:

Marcelo Moraes Valença

Keywords:

Cluster headache

Intranasal herpes

Secondary cluster headache

Herpes simplex

Valacyclovir

Melatonin.

Received: October 6, 2021

Accepted: October 10, 2021

142

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Bernardes LS, Oliveira RD, Peres MFP

Cluster headache due to intranasal herpes simplex: a case report

Introduction

luster headache is a rare kind of primary headache,

accounting for roughly 0.1% worldwide; it is considered

a trigeminal autonomic cephalalgia characterized by pain

in the distribution of the rst division of the trigeminal nerve

along with autonomic features. It has a male predominance

and seems to be more common during spring and autumn.

Cluster headache attacks are dened by severe pain,

orbital, supraorbital, temporal, or a combination of these,

unilateral, lasting from 15 minutes until 180, occurring

up to eight times a day. Headache attacks usually occur

with symptoms such as lacrimation, conjunctival injection,

rhinorrhea, forehead, miosis, ptosis, eyelid edema, and

agitation.

Life habits such as smoking, and head trauma,

are considered risk factors for this illness. Structural diseases

may also cause cluster headache; in a recent systematic

review, the most common pathologies associated were

vascular, tumoral, inammatory and infection. Features

of the history such as late onset and altered neurologic

examination must be considered as red ags and one must

look for secondary causes for the headache. Intranasal

and sinus infectious such as sinusitis and mucocele were

also reported.

Labial and genital herpes are common diseases in the

general population, caused by herpes simplex 1 and 2.

Among people up to 49 years old, it is estimated that the

seroprevalence of herves simplex virus 1 (HSV-1) is as high

as 67% (3.7 billion individuals of the global population).

The nerve ganglia are the natural reservoir of this virus, and

it may be reactivated by trigger factors such as emotional

stress, fever, common cold, trauma, among others.

Intranasal herpes, on the other side, is quite an unusual

site of infection, with only a few cases so far reported in

the literature.

5,6

Our goal is to report a case of cluster headache secondary

to intranasal herpes simplex infection.

Case Report

We report a case of a 43-year-old right-handed man,

presented 2 years ago with a left-sided excruciating pain,

starting in the orbital region irradiating to the ear and nose,

lasting 15 minutes, associated with tearing and ipsilateral

rhinorrhea. He also complained of sleep deprivation and

anxiety; he thus was started on melatonin, subcutaneous

sumatriptan, and oxygen. The headache cycle ended soon

after melatonin, and he did not try sumatriptan or oxygen.

One year later, he presented another cluster headache

cycle with the same features, and he also felt paresthesia in

the left lateral nasal region. An otolaryngologist evaluated

the patient at the emergency department, and rhinoscopy

disclosed lesions in the internal vestibular region of the

nose, hyperemia, and scars suggestive of herpes simplex.

Antibodies IgM and IgG for herpes simplex were positive.

A diagnosis of nasal herpes was made. The patient started

on valacyclovir 500 mg

tid

, and headaches had prompted

relief three days after starting the antiviral therapy. In a

follow-up visit, six months after the treatment, he still was

free of headache attacks.

Discussion

Cluster headache has already been reported to be associated

with herpes simplex infection in a case of a 42-year-old man,

which presented with cluster headache in association with

ipsilateral herpes simplex in 1985.

This report suggested

that the vasodilation seen in cluster headache could be

active by the latent viral infection in the trigeminal system.

Our report seems to be the rst case linking cluster headache

to intranasal herpes simplex infection. IgM and IgG class

antibodies conrm a chronic infection with recent reactivation,

associating the cluster headache with the HSV reactivation

process.

This report supports the role of viral infections as a putative

cause of secondary cluster headache. Herpesviruses or

other underlying infectious diseases might be related to the

mechanisms of triggering cluster headache bouts. It is a

biologically plausible theory because:

1. Neuronal tropism of certain infectious agents - Herpes

simplex virus type 1 can cause serious neurological disease,

such as encephalitis, albeit the precise pathophysiologic

mechanisms remains unclear so far; it is believed that the

infection of the oropharynx may reach the central nervous

system through the trigeminal via or olfactory tracts, and

axonal spread might likewise play a role.

2. It is common in the population - Herpes simplex type 1 is

one of the most common mucocutaneous infections worldwide,

which incidence in 2012 was estimated at 118 million.

Transmission of HSV-1 generally occurs with infected or genital

secretions during asymptomatic shedding. Viral shedding

is characterized as the detection of the herpes simplex virus

from orofacial sites. It is thought that viral shedding from nares

accounts only for 3% of the cases.

Nonetheless, precisely

143

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Bernardes LS, Oliveira RD, Peres MFP

Cluster headache due to intranasal herpes simplex: a case report

intranasal herpes epidemiology remains little known.

3. It may cause pain, and if occurring in the intranasal cavity,

it could mimic cluster headache.

4. An Italian study found high titers of antibody anti-herpes

simplex 1 and 2 viruses in cluster headache patients.

5. HSV can lead to trigeminal ganglion inammation, a

structure known to be involved in the pathophysiology of

cluster headache.

However, there are some arguments against the thought that

herpes is a common or a general cause for cluster headache,

such as:

1. Seasonal variation and circadian rhythmicity – Cluster

headache bouts are seasonal, occurring principally in autumn

and spring and during the transitions from winter to spring.

However, herpes simplex seasonality is controversial – most

authors consider it not seasonal but rather an endemic disease.

In addition, a Korean multicenter study showed that only half

of the patients with active cluster headache had circadian

rhythmicity in the current bout.

4,12

2. Epidemiology of cluster headache and herpes simplex

infection – While herpes simplex infection is quite common

worldwide, cluster headache prevalence is estimated at

0.12%.

Hence, it is unlikely that herpes simplex is one of the

main causes of cluster headache bouts.

Conclusion

Herpes simplex might be involved in secondary or primary

cluster headache mechanisms, and further research is necessary

to help elucidate this relationship. A careful history regarding

previous herpes simplex infections should be considered, and

an intranasal examination should be included in the suspected

cases, as well as laboratory workup for herpes simplex.

Methods to diagnose HSV include viral culture, Tzanck smear,

serology, and polymerase chain reaction.

Leonardo de Sousa Bernardes

https://orcid.org/0000-0001-7448-0666

Renan Domingues Oliveira

https://orcid.org/0000-0002-6058-7937

Mário Fernando Prieto Peres

https://orcid.org/0000-0002-0068-1905

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