Ophthalmology – Migraine & Cluster Headache

Basics

Description

Migraine headache is a chronic, recurrent, episodic primary headache disorder caused by dysfunction of neural pain-processing pathways rather than an underlying intracranial or systemic disease. It may occur with or without aura and is commonly associated with nausea, vomiting, photophobia, and phonophobia.

Cluster headache is a primary trigeminal autonomic cephalalgia characterized by recurrent, short-lived attacks of excruciating unilateral orbital, supraorbital, or temporal pain associated with ipsilateral cranial autonomic manifestations. Attacks characteristically occur in temporal clusters separated by pain-free periods.

Migraine Without Aura – Diagnostic Features

Typical diagnostic criteria include:

• At least 5 attacks
• Individual attacks lasting approximately 4–72 hours
• Headache has at least 2 of:
• Unilateral location
• Pulsating or throbbing quality
• Moderate-to-severe intensity
• Aggravation by routine physical activity or avoidance of activity
• During the headache, at least 1 of:
• Nausea and/or vomiting
• Photophobia and phonophobia
• Not better explained by another disorder

Cluster Headache – Diagnostic Features

Typical features include:

• At least 5 attacks
• Severe or very severe unilateral:
• Orbital
• Supraorbital
• Temporal pain
• Attack duration approximately 15–180 minutes
• Frequency ranging from every other day to several attacks per day

At least one ipsilateral autonomic feature commonly accompanies the pain:

• Conjunctival injection
• Lacrimation
• Nasal congestion
• Rhinorrhea
• Eyelid edema
• Forehead or facial sweating
• Ptosis
• Miosis

Patients may instead or additionally demonstrate prominent:

• Restlessness
• Agitation

Cluster headache has characteristic:

• Circadian periodicity
• Circannual periodicity
• Repeated attacks during a cluster period

Initial Assessment

The first questions are whether the headache is:

1. Primary or secondary
2. New-onset or chronic/recurrent

A typical longstanding migraine with a normal neurologic examination generally does not require extensive investigation.

A first, unusual, rapidly progressive, or neurologically complicated headache requires evaluation for secondary causes.

Red Flags

Urgent evaluation should be considered with:

• Sudden or thunderclap onset
• Maximum severity immediately at onset
• New focal neurologic deficit
• Progressive headache pattern
• Fever or systemic illness
• New headache at older age
• Major change from the patient’s usual headache pattern
• Known malignancy
• Significant immunocompromise
• Headache precipitated by:
• Exertion
• Sexual activity
• Valsalva
• Position change
• Papilledema
• Persistent visual field defect
• Altered consciousness

Epidemiology

Migraine

Migraine is much more common in women.

Typical epidemiologic features include:

• Female-to-male predominance approximately 3:1
• Lifetime prevalence substantially higher in women
• Overall population prevalence roughly 12–15%

Cluster Headache

Cluster headache is much less common than migraine.

Historically it has shown a strong male predominance, although the sex difference is less marked in more contemporary series.

Risk Factors

Family History

A family history of migraine substantially increases the likelihood of developing migraine.

Genetics

Most migraine is polygenic and multifactorial.

Rare monogenic migraine syndromes include familial hemiplegic migraine, in which mutations affecting neuronal ion transport and neurotransmission have been identified.

General Prevention

Prevention begins with identifying and minimizing individual triggers.

Potential migraine triggers include:

• Sleep deprivation
• Excessive sleep
• Irregular sleep schedule
• Stress
• Missed meals
• Dehydration
• Excessive caffeine
• Caffeine withdrawal
• Alcohol
• Hormonal changes
• Certain foods in susceptible patients

A headache diary can help establish individual patterns.

Pathophysiology

Migraine is no longer considered simply a vascular headache.

Important mechanisms include:

• Activation of central pain-sensitive cranial pathways
• Trigeminovascular activation
• Release of neuropeptides such as CGRP
• Central pain sensitization
• Altered serotonergic neurotransmission
• Hypothalamic and brainstem network involvement

Migraine Aura

Aura is strongly associated with cortical spreading depolarization, a slowly propagating wave of neuronal and glial activity followed by temporary suppression of cortical function.

Cluster Headache

Cluster headache involves:

• Trigeminal nociceptive activation
• Parasympathetic cranial autonomic activation
• Hypothalamic mechanisms

Hypothalamic involvement helps explain the striking circadian and circannual pattern.

Etiology

Migraine is generally hereditary and multifactorial.

Multiple genetic and environmental influences contribute.

The exact inheritance pattern for common migraine is not defined.

Commonly Associated Conditions

Migraine has associations with:

• Depression
• Anxiety
• Panic disorder
• Epilepsy
• Asthma
• Other chronic pain syndromes
• Sleep disorders

Diagnosis

History

The history is the most important component of diagnosis.

Assess:

• Inciting event
• Age at onset
• New versus chronic/recurrent headache
• Location
• Quality
• Duration
• Severity
• Frequency
• Time course
• Associated symptoms
• Triggers
• Aggravating factors
• Relieving factors
• Positional relationship
• Valsalva relationship
• Exertional relationship
• Neurologic symptoms
• Visual symptoms
• Previous treatments
• Medication overuse

Time–Intensity Relationship

Subarachnoid Hemorrhage

Classically:

Sudden thunderclap headache with maximal intensity at or very near onset.

Cluster Headache

Typically:

• Reaches severe intensity rapidly
• Often peaks within minutes
• Remains severe for a relatively short period
• Resolves much faster than a typical migraine

Migraine

Typically:

• Builds over minutes to hours
• Persists for hours
• May last up to several days

Migraine-Associated Features

Ask specifically about:

• Aura
• Nausea
• Vomiting
• Photophobia
• Phonophobia

Visual Aura

Migraine aura commonly produces positive visual phenomena.

Typical symptoms include:

• Scintillating scotoma
• Zigzag lines
• Fortification spectra
• Flashing lights
• Shimmering areas
• Expanding visual disturbance

Symptoms usually:

• Develop gradually
• Spread across the visual field
• Resolve completely

A persistent visual field deficit or a fixed homonymous defect should prompt investigation for a structural or vascular cerebral lesion.

Cluster Headache History

Typical cluster headache produces:

• Excruciating unilateral periorbital pain
• Rapid crescendo
• Ipsilateral autonomic symptoms
• Marked agitation or restlessness

During an active cluster period, alcohol can precipitate an attack in many patients.

Additional Symptoms Suggesting Secondary Headache

Ask about:

• Transient visual obscurations
• Vertigo
• Meningismus
• Fever
• Purulent nasal discharge
• Myalgias
• Cognitive dysfunction
• Amenorrhea
• Galactorrhea
• Scalp tenderness
• Jaw claudication
• Focal neurologic symptoms

Also obtain history of:

• Cancer
• Aneurysm
• Immunocompromise
• Recent trauma
• Vascular disease
• New medications

Physical Examination

Perform a complete neurologic examination.

Important components include:

• Mental status
• Cranial nerves
• Motor function
• Sensation
• Reflexes
• Coordination
• Gait

Ophthalmic Examination

Evaluate:

• Visual acuity
• Pupillary responses
• Relative afferent pupillary defect
• Ocular motility
• Alignment
• Visual fields
• Anterior segment
• Intraocular pressure when indicated
• Fundus
• Optic nerve

Between migraine attacks, the neurologic and ophthalmic examinations are generally normal.

Diagnostic Testing

Laboratory Tests

Routine laboratory testing is unnecessary in a classic primary migraine presentation.

Testing should be tailored to the suspected secondary diagnosis.

Possible investigations include:

• CBC
• Platelet count
• Metabolic profile
• ESR
• CRP

Patients Older Than 50

In a patient over 50 with new headache, particularly with:

• Scalp tenderness
• Jaw claudication
• Constitutional symptoms
• Polymyalgia symptoms
• Transient or permanent visual disturbance

consider giant cell arteritis and obtain inflammatory markers urgently.

Additional Laboratory Testing

Selected investigations depending on the clinical picture may include:

• ANA
• Anti-dsDNA
• Thyroid studies
• Arterial blood gases
• Sleep study for suspected obstructive sleep apnea

Testing should be guided by the history rather than ordered indiscriminately.

Imaging

Nonurgent New Headache

When imaging is indicated in a nonemergent setting:

MRI brain is generally preferred because of its superior soft-tissue sensitivity.

Acute Severe or Thunderclap Headache

Initial evaluation commonly includes:

Urgent noncontrast head CT

Further vascular imaging may be required depending on the suspected cause.

MR Venography

MRV is useful when considering:

• Cerebral venous sinus thrombosis
• Idiopathic intracranial hypertension

CTA and MRA

Vascular imaging can be used to evaluate:

• Intracranial aneurysm
• Arteriovenous malformation
• Cervical or intracranial arterial dissection

Lumbar Puncture

Lumbar puncture may be required when:

• Meningitis is suspected
• Intracranial pressure disorders are suspected
• Subarachnoid hemorrhage remains clinically suspected despite nondiagnostic initial imaging

The exact sequence of CT, vascular imaging, and LP depends on timing and clinical circumstances.

Additional Diagnostic Procedures

Visual Aura

Formal visual field testing can help determine whether a persistent defect is:

• Homonymous
• Monocular
• Compatible with retinal/optic nerve disease

A fixed homonymous defect raises concern for retrochiasmal cerebral pathology.

Headache Disability Assessment

Validated instruments may include:

• MIDAS
• HIT-6

These can help quantify functional burden and monitor treatment response.

Differential Diagnosis

Other Primary Headaches

Differentiate migraine from:

• Tension-type headache
• Cluster headache
• Other trigeminal autonomic cephalalgias

A large proportion of self-described “sinus headaches” are actually migraine.

Secondary Headache Causes

Important secondary diagnoses include:

Vascular

• Subarachnoid hemorrhage
• Intracerebral hemorrhage
• Ischemic stroke
• Cervical artery dissection
• Cerebral venous sinus thrombosis
• Intracranial aneurysm
• Arteriovenous malformation

Neoplastic

• Primary brain tumor
• Metastatic disease
• Lymphoproliferative disease

Other

• Meningitis
• Encephalitis
• Idiopathic intracranial hypertension
• Chiari malformation
• Hypertensive emergency
• Giant cell arteritis
• Cranial neuralgia
• Tolosa–Hunt syndrome
• Infectious sinusitis
• Acute angle-closure glaucoma
• Hypercapnia
• Obstructive sleep apnea

Treatment of Migraine

First-Line Acute Treatment

Acute or abortive treatment is preferably administered early in the headache phase.

For mild-to-moderate attacks, options include:

• Acetaminophen
• Aspirin
• Ibuprofen
• Naproxen

An antiemetic may be added when nausea or vomiting is prominent.

Antiemetics

Useful agents include:

• Metoclopramide
• Prochlorperazine

These may:

• Reduce nausea
• Improve gastric motility
• Improve absorption of oral medication
• Have independent antimigraine effects in some patients

Triptans

Triptans are selective 5-HT1B/1D receptor agonists.

Choice should be individualized according to:

• Route of administration
• Speed of onset
• Duration
• Recurrence tendency
• Side-effect profile
• Previous response

They are generally most effective when used early after the headache begins.

Examples include:

• Sumatriptan
• Rizatriptan
• Zolmitriptan
• Eletriptan
• Naratriptan
• Almotriptan
• Frovatriptan

Triptan Precautions

Avoid or use cautiously in patients with significant:

• Ischemic coronary disease
• Previous myocardial infarction
• Certain cerebrovascular diseases
• Poorly controlled hypertension

Older teaching discouraged triptans in hemiplegic migraine and migraine with brainstem aura; management of these unusual disorders should be individualized by a headache specialist.

Medication Interaction Alert

Do not use a triptan and an ergot derivative within 24 hours of one another because of excessive vasoconstrictive risk.

Certain triptans also interact with monoamine oxidase inhibitors (MAOIs) and require drug-specific avoidance periods.

Concurrent SSRI/SNRI and triptan use has historically raised concern for serotonin syndrome; clinically significant serotonin toxicity appears uncommon, but patients should still be educated about symptoms.

Ergot Derivatives

Dihydroergotamine may be used in selected severe or refractory migraine attacks.

Routes include:

• Intravenous
• Intranasal

Antiemetic pretreatment is often required.

Its use is limited by:

• Vasoconstrictive effects
• Drug interactions
• Cardiovascular contraindications
• Availability of newer migraine-specific agents

Second-Line / Refractory Acute Therapy

In monitored emergency or inpatient settings, selected refractory attacks may be treated with agents such as:

• IV antiemetics
• IV NSAIDs
• IV dihydroergotamine
• IV valproate in selected patients
• IV fluids when dehydrated

Corticosteroids are sometimes used to reduce recurrence in prolonged migraine but are not routine first-line therapy.

Opioids

Opioids should generally be avoided or strongly limited because they can contribute to:

• Medication-overuse headache
• Chronification
• Dependence
• Poor long-term migraine control

Migraine Preventive Therapy

Preventive therapy should be considered when attacks are:

• Frequent
• Prolonged
• Severe
• Disabling
• Poorly responsive to acute therapy
• Associated with contraindications to acute drugs
• Causing excessive acute-medication use

Goals are to reduce:

• Frequency
• Severity
• Duration
• Disability
• Need for rescue medication

Preventive medications are titrated gradually according to clinical response and tolerability.

Traditional Preventive Medications

Options include:

Beta-Blockers

For example:

• Propranolol
• Metoprolol

Antiepileptic Medications

Especially:

• Topiramate
• Valproate

Other anticonvulsants generally have less consistent evidence.

Antidepressants

Examples include:

• Amitriptyline
• Venlafaxine

Calcium-Channel Blockers

Certain agents may be used in selected migraine subtypes or particular geographic practice settings.

Modern Migraine Prevention

Modern preventive options also include:

• CGRP monoclonal antibodies
• Oral CGRP receptor antagonists used preventively
• OnabotulinumtoxinA for chronic migraine

OnabotulinumtoxinA is particularly useful in appropriately selected patients with chronic migraine, rather than occasional episodic migraine.

Cluster Headache – Acute Treatment

Because attacks are brief and extremely severe, therapy must act rapidly.

High-Flow Oxygen

A major first-line treatment is:

100% oxygen through a non-rebreather mask

High flow rates are typically used for approximately 15–20 minutes or until the attack subsides.

Sumatriptan

A highly effective acute treatment is:

Subcutaneous sumatriptan

Intranasal triptans may also be used when injections are unsuitable.

Other Acute Cluster Treatments

Selected alternatives include:

• Intranasal triptans
• Intranasal lidocaine in some patients
• Dihydroergotamine in selected circumstances

Cluster Headache Preventive Therapy

Verapamil

Verapamil is a principal first-line preventive medication for cluster headache.

Dose is titrated according to response.

Because it can produce:

• Bradycardia
• PR prolongation
• Heart block

ECG monitoring is important during dose escalation.

Corticosteroids

A short course of corticosteroids may provide transitional or bridging therapy while a longer-term preventive treatment becomes effective.

They are not generally intended for prolonged prophylaxis.

Lithium

Lithium may be particularly useful in:

• Chronic cluster headache
• Refractory cases

Monitoring includes:

• Serum lithium concentration
• Renal function
• Thyroid function
• Electrolytes

Pediatric Considerations

Migraine occurs in children and adolescents.

Important measures include:

• Regular sleep
• Adequate hydration
• Regular meals
• Avoiding excessive caffeine
• Limiting medication overuse
• Age-appropriate acute therapy

Emergency therapy may include antiemetics plus analgesics when indicated.

Preventive therapy is individualized according to:

• Frequency
• Disability
• School impact
• Comorbidities

Pregnancy Considerations

Nonpharmacologic approaches are emphasized whenever possible.

Acetaminophen is commonly used for acute attacks.

Medication choice requires individual risk-benefit assessment because several migraine drugs are undesirable or contraindicated during pregnancy.

Important points include:

• Avoid indiscriminate NSAID use, especially later in pregnancy.
• Valproate should generally be avoided in pregnancy because of major fetal risks.
• Ergot derivatives are contraindicated.
• Preventive therapy requires specialist guidance.

A new, severe, or altered headache during pregnancy should not automatically be attributed to migraine. Consider:

• Preeclampsia/eclampsia
• Cerebral venous thrombosis
• Reversible cerebral vasoconstriction syndrome
• Pituitary disease
• Intracranial hemorrhage

Additional Treatment

General Measures

Management should be individualized according to:

• Attack characteristics
• Frequency
• Severity
• Disability
• Associated symptoms
• Comorbidities

Associated conditions should also be addressed, including:

• Obesity
• Anxiety
• Depression
• Sleep disorders

Issues for Referral

Neurology or headache-specialist referral is appropriate for:

• Chronic migraine
• Frequent disabling headaches
• Status migrainosus
• Medication-overuse headache
• Complex aura
• Hemiplegic migraine
• Migraine with brainstem symptoms
• Unclear diagnosis
• Failure of standard prophylaxis
• Recurrent emergency visits
• Need for advanced preventive therapy

Additional Therapies

Nonpharmacologic strategies may include:

• Cognitive behavioral therapy
• Relaxation training
• Biofeedback
• Regular aerobic exercise
• Consistent sleep
• Stress management

Supplements with some evidence in migraine prevention include:

• Magnesium
• Riboflavin
• Coenzyme Q10
• Melatonin in selected patients

Evidence and optimal dosing vary.

Complementary and Alternative Therapies

Acupuncture

May provide benefit for some patients with migraine prevention.

Butterbur

Older literature suggested benefit, but butterbur is generally not favored because of concerns about hepatotoxic pyrrolizidine alkaloids and product purity.

Feverfew

Evidence is inconsistent.

Hyperbaric Oxygen

Hyperbaric oxygen is not routine migraine therapy.

This should not be confused with high-flow normobaric oxygen, which is an established acute treatment for cluster headache.

Procedures

OnabotulinumtoxinA

Effective for appropriately selected patients with chronic migraine.

Occipital Nerve Procedures

Occipital nerve block or neuromodulation may be considered in highly selected refractory headache syndromes.

Occipital nerve stimulation is generally reserved for severe treatment-resistant disease.

In-Patient Considerations

Admission Criteria

Admission may be necessary for:

• Intractable headache
• Status migrainosus
• Severe dehydration
• Recurrent vomiting
• Need for monitored intravenous treatment
• Medication-withdrawal protocols
• Uncertain secondary headache requiring further workup

IV Fluids

IV isotonic fluids may be given when:

• Oral intake is inadequate
• Significant vomiting has caused dehydration

Routine IV hydration is not itself a specific migraine treatment in a normally hydrated patient.

Nursing

Routine monitoring is appropriate, with additional observations determined by:

• Medication administered
• Cardiovascular status
• Neurologic status
• Secondary headache concern

Discharge Criteria

Discharge is appropriate when:

• Dangerous secondary causes have been excluded when necessary
• Headache has substantially improved
• Oral hydration is adequate
• Neurologic status is stable
• A safe outpatient treatment plan is established

Ongoing Care

Follow-Up Recommendations

Follow-up depends on response to treatment.

Care may be coordinated through:

• Primary care
• Neurology
• Headache specialist

Patient Monitoring

After an emergency visit or major medication change, earlier reassessment may be appropriate, often within approximately:

1–2 weeks

Poorly controlled headaches may require follow-up every:

2–4 weeks

until a stable regimen is achieved.

Once stable, visits can become less frequent.

Diet and Lifestyle

Patients should be encouraged to:

• Eat regular meals
• Maintain adequate hydration
• Avoid excessive caffeine
• Avoid large fluctuations in caffeine intake
• Identify genuine food triggers rather than imposing unnecessary dietary restriction
• Maintain a balanced diet

Skipping meals is a common migraine precipitant.

Patient Education

Patients should understand:

• Their headache diagnosis
• Expected course
• Individual triggers
• Appropriate use of acute medications
• Preventive medication goals
• Potential adverse effects
• Importance of lifestyle regularity
• Risks of medication overuse
• When to seek urgent medical attention

Medication-Overuse Headache

Frequent use of acute medication can itself produce or perpetuate chronic headache.

Common culprits include:

• Combination analgesics
• Opioids
• Triptans
• Ergot derivatives
• Frequent simple analgesic use

Recognition and withdrawal of the overused medication are essential parts of management.

Prognosis

The long-term course of migraine is variable and multifactorial.

Many patients experience:

• Fluctuating frequency over time
• Periods of remission
• Improvement with appropriate preventive therapy
• Changes in pattern with age and hormonal status

Cluster headache likewise varies, with some patients having episodic cluster periods separated by prolonged remissions and others developing chronic disease.

Complications

Important complications include:

• Chronic migraine
• Chronic daily headache
• Medication-overuse headache
• Status migrainosus
• Disability affecting work or school
• Anxiety and depression
• Excessive emergency-care use
• Adverse effects from medications

Rare neurologic complications related to migraine include persistent aura and migrainous infarction.

Ophthalmology Pearls

• Migraine aura usually consists of positive visual phenomena that develop gradually and resolve completely.
• Migraine visual aura is usually binocular/homonymous, even when the patient describes it as affecting “one eye.”
• A true episode of monocular transient visual loss should prompt consideration of retinal or optic nerve ischemia rather than automatically being labeled migraine.
• A fixed homonymous visual field defect requires investigation for a retrochiasmal lesion.
• Cluster headache commonly causes ipsilateral lacrimation and conjunctival injection.
• Cluster headache can produce a transient partial Horner syndrome with ptosis and miosis.
• Headache plus a painful red eye requires exclusion of acute angle-closure glaucoma.
• Headache plus papilledema suggests raised intracranial pressure and requires investigation.
• In a patient older than 50 with a new headache and visual symptoms, always consider giant cell arteritis.
• A first or “worst-ever” thunderclap headache should be treated as a potential vascular emergency rather than presumed to be migraine.