Recurrent Epistaxis: An Unusual Manifestation of Clinical Spectrum of Migraine -Case Series with Scoping Review of Literature

Abstract

Objective: We report four cases of migraine induced epistaxis and reviewed the published literature of migraine with epistaxis to establish demographic profiles, types of migraine, severity, family history of headache and other associated disorders in adults. Methods: A panoramic search of the Medline database through Pubmed was done in May 2022 using search terms: {Migraine with Epistaxis}, case reports. All articles/case reports in English from January 2001 to April 2022 where age of patients was > 18 years were included in our review. Results: Our search recognized total of three cases and with inclusion of the four cases who reported to us, we reviewed these seven cases and studied demographic profile, clinical features, association of epistaxis with types and severity of migraine and relationship with other medical disorders. Mean age of presentation was 28.7 years (range 18–49), with five female and two male patients. The intensity of headache was severe in three of seven cases and there was one case each of moderate and mild category. Five of seven (71%) patients had reduction in intensity of headache with onset of bleeding and various types of migraine (Migraine with and without Aura, vestibular migraine, sporadic familial hemiplegic migraine) according to ICHD classification were associated with epistaxis. Four of seven had positive family history of migraine. There was no diagnostic finding in any patient and all patients responded to migraine preventive medication. Conclusion: Recurrent epistaxis is not so uncommon manifestation of various types of migraine and specialist should keep this clinical diagnosis in mind to avoid misdiagnosis.

Introduction

Headache is a very common condition in all age groups and migraine is the first involving order of frequency in both adult and paediatric community. It is seen that migraine is the topmost reason of primary headache among children [1]. Migraine attacks are marked by diverse symptoms which involves the sensory system with manifestations such as photophobia, phonophobia, allodynia, osmophobia and muscle pain; accompanied with autonomic symptoms like nausea, vomiting, lacrimation, nasal congestion, cognitive disability with temporary forgetfulness, word-finding struggle, irritability and depression Migraines are self-limiting impairment of grey matter. It is primarily a neuronal sensory dysfunction which secondarily involves the vascular system. Involvement of the sensory nerve fibers within meningeal blood vessels gives rise to head pain [2].

There are varied clinical presentations of migraine spectrum some of them being not so common like epistaxis [3] which may lead to misdiagnosis further leading to erroneous management. There are few published literature regarding varied presentation of migraine symptoms .Abdominal colic ,benign paroxysmal vertigo ,cyclical vomiting syndrome [1] are known migraine equivalents also identified in ICHD-3 (International Classification of Headache Disorders [4]. Established literature reveals association with other comorbid conditions like allergy, asthma, sleep disturbances and seizures [5]. Although association of nose bleed with migraine is not an uncommon symptom [6] yet there are very few published case reports/series or review of literature in adults.

Epistaxis or nose bleed is a very common complaint in both paediatric and adult population. 60% of population experience at least one episode of nose bleed and 6% seek medical help [7].

Specialists are not much aware of this co-occurrence of the condition of migraine and nose bleeds leading to a clinico-diagnostic dilemma. Up till date very few cases have been published worldwide. It is mainly characterized by spontaneous nasal bleed accompanied with migraine headache and associated features of nausea, vomiting, photophobia phonophobia etc. It is often first reported to the otolaryngologists for nasal bleeds and this is the reason why otolaryngologists should be familiar with the condition of co-occurrence of epistaxis with migraine.

Most of the times both these common entities are tackled individually. Epistaxis due to migraine is not well studied especially in adult population so our knowledge regarding spectrum of migraine associated with nasal bleeds, its outcome and the therapeutic profile is limited.

It is a clinical diagnosis as there are no objective tests to diagnose and these patients can present with troublesome varied symptoms thereby causing confusion among otolaryngologists, neurologists, ophthalmologists and psychiatrists depending upon the initial presentation. We presume that migraine induced epistaxis is an under diagnosed condition.

The aim of this case series and review is to augment awareness of this enigmatic condition among specialists so as to keep a differential of migraine induced epistaxis in mind for correct timely diagnosis so as to prevent delay in treatment resulting in physical and psychological repercussions.

Here we present four cases of migraine induced epistaxis who reported to us in the ENT department in our Medical College Hospital. They were examined by ear, nose and throat specialist and ophthalmologist. Data regarding the following parameters were collected: patient demographics, clinical presentation including detailed medical history, complete eye examination relevant diagnostic assessments like blood tests to rule out bleeding/clotting disorders; diagnostic nasal endoscopy, brain MRI, auditory evaluation, fundoscopy and Spectral-domain optical coherence tomography (OCT) wherever required. Treatment protocol, and response to treatment was also documented.

Case I

18-year old male presented to ENT OPD with history of recurrent nasal bleed since six months. History of mild nasal blockade(right) off and on and severe headache persisting for few hours associated with nausea and photophobia. History of unilateral headaches since one year which aggravated when he used his laptop in excess and was associated with photophobia and blurring of vision. Patient emphasized that bleeding always followed severe throbbing headache usually on the same side as that of headache. The intensity of headache reduced after bout of nosebleed. There was no history of trauma, bleeding disorder or intake of drugs.

On examination we performed Diagnostic Nasal Endoscopy which showed asymptomatic right deflected nasal septum with normal nasal patency (Fig. 1). Endoscope could be negotiated in both nasal cavities and there was no spur, mass, raw area or bleeder seen. Differential diagnosis of Sluder’s neuralgia with DNS (Deflected Nasal Septum ) (RT) with epistaxis was made but we could not explain opposite side headache with nose bleed.

Fig. 1.

Diagnostic Nasal Endoscopy depicting right sided deflected nasal septum. No discharge, blood clot or raw area seen in nasal cavity

Patient was referred to ophthalmology OPD for opinion and examination revealed normal visual acuity, anterior segment and Fundus examination. The IOP (Intraocular pressure with Goldmann applanation tonometry) Humphreys visual field perimetry and OCT were all within normal limits.

The patient was sent for investigations: Haematological parameters especially coagulation profile and MRI Brain did not show any abnormality.

The characteristic of headache in this patient was compatible with migraine without aura according to ICHD 3 classification [4].

We started him with tablet flunarizine one tablet daily with lifestyle and dietary modification. He did not have single episode of nasal bleed in four months follow up and his frequency and intensity of headache also reduced.

Case II

A 19-year old female was referred from medicine OPD with complaints of recurrent nasal bleeds and headache. Headache was unilateral associated with vomiting, phonophobia and photophobia. She had history of seizures since childhood and was on treatment. History of frequent abdominal colic was positive during childhood. Patient complained of headache after seizure episodes. We made a differential diagnosis of Post ictal headache but patient denied any history of seizures for past two years. There was no history of nasal discharge, blockade or trauma.

She underwent complete ENT examination to rule out any organic pathology and no structural abnormality was detected.

A blood workup was done which was normal. Her MRI Brain axial section revealed (Fig. 2) focal area of blooming in the right parietal cortex at the level of corona radiata.

Fig. 2.

Gradient echo imaging axial section at level of corona radiata showing a focal area of blooming in the right parietal cortex(may represent focal area of calcification due to calcified granuloma/hemosiderin deposit due to chronic microhaemorrhage)

She underwent eye examination which showed normal visual acuity. Her anterior and posterior segment evaluation were all within normal limits.

After examination and investigations, we made diagnosis of Migraine without aura according to ICHD-3 with epistaxis.

We started with 10 mg tablet flunarizine which led to reduction in all the symptoms. This patient was from a remote village so could not come back again for follow up due to pandemic lockdown but telephonically informed us about her wellbeing.

Case III

A 23-year-old female presented to ENT OPD with complaints of spontaneous nose bleeds often at night off and on. There was no history of any nasal blockade, sneezing, PND (Post nasal discharge )or nose picking. Patient complained of mild to moderate pulsatile headache associated with dizziness for 5 to 10 min. Dizziness was triggered by postural change and associated with nausea, aural fullness, photophobia and blurring of vision. All her headache episodes were not accompanied with dizziness but dizziness always followed headache and few of these episodes accompanied with nose bleeding. Patient observed occasional nasal bleed during sleep which was associated with mild headache. There was no effect on severity of headache with episode of nose bleed. Thorough ENT examination ruled out any obvious cause and no structural abnormality was detected. Audiological evaluation: Pure tone audiometry was done at 250 Hz,500 Hz 1 kHz ,2 kHz 4khZ and 8 Khz for air conduction and at 250 Hz,500 Hz 1 kHz ,2 kHz 4khZ for bone conduction with showed pure tone average of 18dB and 20 dB in Right ear and left ear respectively. Impedance audiometry done with 226 Hz tone showed Bilateral A type tympanogram with both ipsilateral and contralateral reflexes present. Eustachian tube function test was also done which showed normal Eustachian Tube Function in both ears. Patient was referred to ophthalmology OPD where ocular examination revealed no abnormality. A coagulation profile and neuroimaging MRI Brain were normal. (Fig. 3).Diagnosis of Vestibular migraine according to ICHD − 3 was made with epistaxis. We started her with flunarizine but had to change to propranolol 40 mg as patient complained of excessive sleepiness and weight gain.

Fig. 3.

T2 weighted axial section at level of ganglio capsular region showing normal signal intensities in gray- white matter and bilateral lateral ventricles

Case IV

20-year-old female was referred from medicine OPD with complaints of intermittent episodes of a brief epistaxis accompanied with visual flashing, dizziness, aural fullness, tinnitus, confusion, slurry speech, and visual impairment both eyes followed by migraine headache. There was no history of loss of consciousness. She had an episode of nasal bleed during acute headache, few drops from both sides which stopped by itself in a short while. ENT examination was normal and there was no abnormality detected on DNE.

Her audiological examination showed pure tone average of 20 dB and 15 dB in Right ear and left ear respectively. Impedance audiometry done with 226 Hz tone showed Bilateral A type tympanogram with both ipsilateral and contralateral reflexes present. Eustachian tube function test was also done which showed normal Eustachian Tube Function in both ears. Her ophthalmological examination did not reveal any abnormality Her blood parameters were normal and as patient suffered from claustrophobia so refused for MRI Brain. We made diagnosis of Migraine with brainstem aura according to ICHD − 3 with epistaxis. Tablet Flunarizine 10 mg was started and follow up at two months, patient did not reveal any nasal bleed episode and there was marked improvement in other symptoms.

Methods

We conducted a literature search to establish patients clinical profile types of migraine (as per ICHD classification), severity of headache and its association with epistaxis for all adult patients. The severity of headache was measured by GAMS (Global Assessment Of Migraine Severity ) score. The patients were asked to answer a single query with seven feedback categories. The response choices were formulated with frequently used seven-point Likert scale. It was a single question directly asked from patients conveying their perception about severity. GAMS is rated for severity of migraine headache and is ideal for busy settings to assess the same [8]. All pertinent literature were taken into account including abstracts, case reports ,case series and reviews. To our surprise there was no available data with MeSH terms {migraine with epistaxis}.

A panoramic search of the Medline database through PubMed was done in May 2022 using search terms: {Migraine with Epistaxis}. Articles in English from January 2001 to April 2022 were thoroughly read in detail and assessed for eligibility of inclusion criteria. We included all case reports with patients above 18 years of age. Data on clinical presentation of patients, including demographics, type and severity of migraine, family history, diagnostic assessments were collected. In our search there was no sufficient data to establish any association of epistaxis with family history of migraine, its type, severity of headache, other clinical features and relationship with associated disorders.

Results and Discussion

Our search of the scientific literature returned eleven studies and all were read in detail. Four studies were case reports of migraine with epistaxis but one study depicted topiramate given for prevention of migraine as cause of epistaxis so was not included in our review. Table 1 shows demographics, clinical findings and other medical disorders of the seven patients including the four cases reported in this article.

Table 1.

summarizes the Demographic data, Signs and Symptoms upon presentation, Medical history & Medical therapy

S No	Author /Year/ Reference	Age /Sex	Headache Freq Severity		Family history of Migraine	Association of pain with nasal bleed	Other clinical features	Any other disorder	Type of Migraine ICHD-3 Criteria	Treatment
1	E Duran Ferreras & J Viguera (2007) 11	25/F	1 per 2 months	NR	Yes Maternal	Reduction with onset of bleed	Nausea, phono-photophobia		Migraine without Aura	1000 mg Paracetamol
2	Jose Barros ,Joana Damasio (2012) 13	47/M	NR	NR	Not mentioned (23 year old son + )	Headache reduce with onset of bleed	Nausea ,photo -phonophobia scotoma Aphasia	Crural weakness & Sporadic Hemiplegia	Migraine with brainstem aura & Sporadic Hemiplegic Migraine	Paracetamol /Nimusulide
3	A Ranieri A Tepa (2014) 20	49/F	NR	Very Severe(6)	Not Reported	Reduction with onset of bleed	Stabbing headache	Raised ICT	Chronic Migraine	Acetazolamide 250 mg twice daily
4	B Shenny et al. 2021	18/M	1–2/Month	Quiet severe(5)	No	Reduction after bleed	Nausea, Phonophobia	DNS (Right) with spur	Migraine without Aura	Tablet Flunarizine 10 mg 1 tablet daily
5	B Shenny et al. 2021	19/F	2/3 Month	Somewhat severe (3)	Yes Maternal	Reduction	Nausea vomiting	Seizures	Migraine without Aura	Tablet Flunarazine 5 mg 1 tablet at bedtime
6	B Shenny et al. 2022	23/F	2/Month	Little severe (2)	Yes Maternal	No effect	Dizziness, nausea vomiting phonophobia,photophobia aural fullness and tinnitus		Vestibular migraine	Tablet flunarizine 10 mg 1 tablet at bed time initially but changed to Propranolol LA
7	B Shenny et al. 2022	21/F	1/Month	Severe(5)	Yes Paternal	No effect	Nausea, vomiting, photopsia ,phono and photophobia, aural fullness	Bronchial Asthama during childhood	Migraine with Brainstem Aura	Tablet Flunarazine 10 mg 1 tablet at bed time

Mean age of presentation was 28.7 years (range 18–49) with five females and two male patients as also reported by Kfah K et al. [9]. It was seen that headache was severe in three of seven cases. There was one case, each of moderate and mild category. In two cases severity of headache was not mentioned. We speculate that the severity of headache did not correlate with epistaxis as seen in our cases. We noticed that even with mild severity of headache, the patients had episodes of epistaxis (Table 1, Case 5,6,7). One of our case complained of nose bleed while sleeping (Table 1, case 6). There is high incidence of bleeding during sleep that has also been mentioned in previous studies although this study was conducted on children [3].

Five (Table 1, Case 1,2,3,4,5) of seven (71%) patients reported reduction in severity of headache with onset of bleeding. In one patient nose bleed did not have any effect on headache and the other case did not mention it. This was in contrast to the study conducted by Awati which showed reduction in intensity of headache in 28% of patients after bout of epistaxis [10].

In four (Table 1, Case 1,5.6.7) of seven cases family history of Migraine was positive mostly on maternal side { Case 1,5,6} [11]. Studies have shown that positive paternal family history of migraine is also a predisposition to migraine with epistaxis [10]. Previous literature also shows genetic predisposition to migraine [12]. This depicts that family history could be an important determinant to predict predisposition to nose bleeds.

These patients also reported with other symptoms. Six patients had nausea (Table 1, Case 1,2,4,5,6,7), five complained of phonophobia (Table 1 ,Case 1,2,4,5,6). Two of our patients had aural fullness (case 6 and 7) and one of them reported tinnitus too (case 6). Four had photophobia (Table 1, Case 1,2,6,7) one patient reported photopsia (case 7) and one case (Table 1, Case 2) had scotoma [13]. Dizziness for few minutes which was less than 15 min occurred in two of our patients (Table 1, Case 6, 7).

Previous literature reveals that phonophobia, tinnitus and dizziness result from vasospasm of small arterioles in cochlea and labyrinth or vasospasm of internal auditory artery or migrainous infarction. Probably spasm of cochlear vessels lead to reversible hypoxic injury producing temporary symptoms [14].

It is observed that up to 80% patients of migraine experience photophobia during an attack [15]. Drummond [16] exhibited that migraineurs were more sensitive to light both during and between migraine headache attacks compared with non-migraine controls. Patients may experience sensory symptoms, speech problems, and sometimes motor symptoms during their auras. Slow expansion is thought to be the most typical sign of a migraine aura which coincides with the suspected underlying pathophysiological phenomena known as cortical spreading depolarization” {CSD} [17].

There was no temporal relationship of these symptoms with commencement or cessation of nasal bleed. 30–60% of migraine attacks are activated by glare or light. Various visual stimuli are known to induce migraine. These include flickering from motion pictures, sunlight, television, and fluorescent lights [17]. This could be the reason of headache stimulation in our case (Table 1, Case 4) whose headache got triggered due to excessive usage of laptop.

According to ICHD-3 classification of migraine we observed three cases were migraine without aura (Table 1, Case 1,4,5) one case of chronic migraine (Case 3), one case of vestibular migraine (Case 6), two cases of migraine with brainstem aura (MBA) (Table 1, case 2,7) out of which one had concomitant sporadic hemiplegic migraine along with MBA (Case 2). Few earlier studies have shown both types of migraine with and without aura to be associated with epistaxis [9] but our review shows that type of migraine does not have predilection with epistaxis and any type of migraine may be associated with epistaxis. We had one case of vestibular migraine (Table 1, Case 6) which has never been reported earlier. Perhaps this could be because both migraine and epistaxis cause stimulation of the trigeminovascular system (TVS) leading to vasodilatation of branches of internal and external carotids. It is proven that stimulation of TVS increases extracerebral flow [18] and epistaxis is the commonest manifestation of this activation [19]. Eventually the vasodilatation caused leads to oligemia, stimulation of perivascular nociceptive nerves resulting in epistaxis and headache [18, 19].

We also noted that four of seven patients had other medical history, one patient (Table 1, case 3) had added clinical feature of stabbing headache suggestive of raised intracranial pressure. She also showed a bilateral narrowing of transverse sinuses at MR-venography. A possible intracranial hypertension was presumed despite the lack of papilledema [20]. It was speculated that the abrupt reorganization of collapsed adjuvant veins of the anterior venous circle, perhaps prompted by periodic waves of central venous hypertension coupled with intracranial hypertensive peaks, led to stabbing headache and epistaxis.

Our first patient (Table 1, Case 4) also complained of nose blockade perhaps due to right sided deflected nasal septum(DNS) (Fig. 1) Although DNS was a structural defect but it lead to delay in our final diagnosis as we presumed that headache was due to DNS giving rise to nose bleed. It was much later when this patient emphasized that nose bleed always followed headache which was always accompanied with nausea and photophobia. Although unilateral yet could occur on any side followed by bleeding from the same side of the nasal cavity. This lead us to the diagnosis of migraine without aura.

One patient had history of seizures and abdominal colic (Table 1, Case 5) and another patient complained of bronchial asthma during childhood (Case 7).

There have been previous studies mostly conducted on children and adolescents which showed association between seizures or epilepsy and migraine [5, 21] as both of them are paroxysmal disorders marked by brief cerebral dysfunction and share some clinical similarities. Both the disorders fall under Channelopathies, the diseases which develops due to defects in ion channels either due to genetic or acquired factors [22]. This patient also gave history of abdominal colic during childhood and established literature suggests possibility of patients of childhood abdominal migraine to develop typical migraine headache in adulthood although exact pathophysiology of underlying abdominal migraine is not known [23, 24].

Another patient (Case 7) had comorbid condition of bronchial asthma. Previous clinical studies did show an association between migraine and asthma both in adults and children [25, 26] The inflammatory mediators especially mast cells, underlying atopic disorders could be blamed for the comorbidity of bronchial asthma and migraine which may be basis of development of headache [27].

It a clinico-diagnostic dilemma thereby a therapeutic challenge as none of our patients had any positive finding during ORL examination, investigations: coagulation test, audiological and ophthalmological examination. Neuroimaging of one of our patient (case 5) showed calcified granuloma which could also be considered as the cause of seizures in our case.

There is no distinct therapy for migraine equivalents and same preventive medication used for migraine can be used for this condition perhaps because of same pathophysiological phenomena they share with migraine [1] We prescribed Propanolal ( Table 1, Case 6) and Flunarizine(Case 4, 5,7) to our four patients along with lifestyle modifications and all of them responded well with no further nose bleeds as well as reduction in intensity and frequency of headache. Flunarazine in previous study also showed good response, not only in reducing frequency and severity of headache but also cessation of nose bleed [28] as Flunarizine interferes the mechanisms probably involved in migraine pathogenesis. It restrains the vasoconstriction, inhibition of “spreading cortical depression” (in experimental conditions) and also plays role in modulation of few neurotransmitters which may be involved in the multifactorial genesis of migraine, thus responsible for its efficacy in the prevention of this disease.

To our surprise, inspite of migraine with epistaxis not being an uncommon condition yet there were sparse published literature especially on adult population. The scarcity perhaps is due to lack of guided dossier.

We do not know the exact prevalence of migraine with epistaxis but one of the study showed it to be 11.83% [9] and another review by Peretz [19] showed rare presentation of extracranial bleeds in headache patients (24%) and epistaxis(63%) to be the commonest form of spontaneous extracranial bleed in migraine .

The diagnosis of Migraine associated epistaxis is thus complicated firstly due to lack of any benchmark investigation secondly perhaps not being common, many clinicians are not aware of this co- occurrence. Most of the standard textbooks do not mention migraine to be one the causes of epistaxis thereby we presume this must be misdiagnosed condition leading to unnecessary investigations, delay in appropriate treatment and wastage of time and money.

It is a clinical diagnosis and these patients can present with troublesome varied symptoms like blurring of vision or epistaxis etc. with headache thereby causing confusion to otolaryngologists, neurologists, ophthalmologists or psychiatrists depending upon the initial presentation.

Inspite of proven association of migraine with epistaxis [6, 29] yet there are no systematic or evidence based reviews published so far. There have been few studies of migraine associated with nose bleed conducted on children [3] but very few articles have been reported for adult population [28]. We observed in our review that after the first report in 2007 by Ferreras and Viguera [11], total of only three cases of migraine induced epistaxis (excluding our cases ) have been published so far.

In our review we tried to evaluate the demographics, type of migraine, family history, clinical features, severity of headache, associated disorders, diagnostic assessment and treatment outcome. We observed that there have been no similar studies done previously to find out these association of migraine with epistaxis.

Conclusion

As it is a clinical diagnosis it should be a routine practice and mandatory for clinicians to take detail history of patients of epistaxis and to keep migraine as a differential. This will not only help us in better understanding but also determine the prevalence of load of this disease. We presume it to be an underdiagnosed condition as it is an uncommon manifestation of a common disorder. We are aware of the issues and lacunae in previous research and we suggest few feasible ways in which our conviction regarding association of migraine with epistaxis shall be more authentic.Firstly, most of the earlier studies to find prevalence and association of this episodic disorder have been conducted on children. So we infer more longitudinal research preferably multicentric are required especially in adults to substantiate the association between the two.Secondly, deficiency of nutritional vitamins or minerals, dietary habits, lifestyles, detailed neuroimaging to see any structural difference in MRI brain of migraineurs and controls should be investigated.Lastly, this should be also recognized as an independent episodic syndrome entity associated with migraine by ICHD .All this will hopefully allow us to have a better knowledge and understanding regarding this association.

Authors’ Contribution Statements

Dr Shenny Bhatia: Patient evaluation, Manuscript writing, literature search, Proof Reading.

Dr Vishwa Jyoti Bahl: Patient evaluation & Manuscript writing.

Dr Monika Sharma: Patient evaluation and Literature search.

Ms Deepika Sharma: Proof Reading and correction.

Dr Vipan Gupta: Proof Reading and correction.

Dr Manpreet Singh Nanda: Proof reading and correction.

Dr Pooja Thakur: Proof reading and correction.

Funding

The study was conducted without any funding or sponsorship.

Data

All data pertaining to study is availabe with the corresponding author.

Declarations

Competing Interests

The authors have No conflict of interest to declare.

Ethics Approval

Not applicable as case series review with review of literature.

Consent

Consent was obtained from patients for inclusion in study.