Overview
Migraine with brainstem aura (MBA) is a subtype of migraine characterized by neurological symptoms originating from the brainstem, often preceding or accompanying the headache phase. These aura symptoms can include vertigo, imbalance, tinnitus, and visual disturbances distinct from typical migraine auras originating from cortical regions. MBA significantly impacts quality of life due to its debilitating nature and potential for prolonged episodes. It predominantly affects adults, though pediatric cases can occur. Accurate diagnosis and tailored management are crucial in day-to-day practice to mitigate symptom severity and frequency, improving patient outcomes and functionality 1.Pathophysiology
The pathophysiology of Migraine with Brainstem Aura (MBA) involves complex interactions at multiple levels of the nervous system. Central to the understanding is the concept of cortical spreading depression (CSD), a wave of neuronal and glial depolarization that spreads across the cerebral cortex. Although traditionally linked with cortical auras, recent evidence suggests that CSD may extend to involve brainstem regions, triggering brainstem aura symptoms 1. This spread of CSD can activate the trigeminal nerve system, contributing to headache pain and potentially sensitizing pain pathways in the brainstem and spinal trigeminal nucleus 5. Additionally, activation of brainstem metabotropic glutamate receptors has been implicated in modulating nociceptive pathways, suggesting a role in the sensitization and maintenance of pain associated with MBA 4. The involvement of calcitonin gene-related peptide (CGRP) and its receptors further complicates the pathophysiology, as CGRP plays a significant role in neurogenic inflammation and pain amplification, processes likely exacerbated in MBA 13.Epidemiology
The precise incidence and prevalence of Migraine with Brainstem Aura (MBA) are not well-documented compared to more common migraine subtypes. However, it is recognized as a less frequent variant within the broader migraine spectrum. Studies suggest that brainstem aura symptoms occur in approximately 0.4% to 1.6% of migraine patients 1. MBA tends to affect adults, with a slight female predominance, though pediatric cases have been reported. Geographic and cultural factors do not appear to significantly influence its prevalence, but specific risk factors such as genetic predisposition and comorbid conditions like anxiety or depression may play roles in its development 3. Trends over time indicate an increasing awareness and reporting of MBA, possibly due to enhanced diagnostic criteria and clinician education, though robust longitudinal data are lacking.Clinical Presentation
Migraine with Brainstem Aura (MBA) presents with characteristic neurological symptoms originating from the brainstem, often preceding or concurrent with headache. Typical aura symptoms include vertigo, imbalance, tinnitus, and transient visual disturbances like scotomas or visual field defects that differ from those seen in cortical auras. Patients may also report nausea, photophobia, and phonophobia. Hypomotility, characterized by reduced motor activity due to fear of exacerbating headache, is another notable feature. Red-flag symptoms that warrant immediate referral include sudden onset of severe vertigo, focal neurological deficits, or speech disturbances, which may indicate conditions like basilar artery migraine or other serious neurological disorders 1.Diagnosis
Diagnosing Migraine with Brainstem Aura (MBA) requires a thorough clinical history and exclusion of other neurological conditions. The diagnostic approach involves:Detailed History: Comprehensive assessment of aura symptoms, their timing relative to headache onset, and associated features like photophobia and hypomotility.
Exclusion of Other Conditions: Rule out secondary causes of headache such as structural brain lesions, vascular disorders, and other neurological diseases through neuroimaging (MRI) and appropriate neurological examinations.
Criteria: Diagnosis aligns with criteria outlined in the International Classification of Headache Disorders (ICHD-3), specifically:
- Aura Symptoms: At least one aura symptom originating from the brainstem, lasting 5-60 minutes.
- Symptom Profile: Symptoms include vertigo, imbalance, tinnitus, and visual disturbances distinct from typical cortical auras.
- Headache Onset: Headache follows aura symptoms within 60 minutes.
- Frequency: Occurring on <15 days per month for >3 months.
- Exclusion: Absence of other neurological or systemic disorders explaining the symptoms.
Tests:
- Neuroimaging: MRI to rule out structural abnormalities.
- Electroencephalogram (EEG): May be considered if seizures are suspected.
- Blood Tests: To exclude systemic causes like infections or metabolic disorders.Differential Diagnosis:
Basilar Migraine: Distinguished by more severe neurological deficits and often bilateral symptoms.
Vestibular Migraine: Primarily characterized by vertigo without prominent brainstem aura symptoms.
Cerebrovascular Events: Sudden onset of focal neurological deficits may indicate stroke or transient ischemic attack, requiring urgent neuroimaging and vascular imaging.Management
First-Line Treatment
Acute Management:
- Triptans: Sumatriptan (50-100 mg subcutaneously or orally) can alleviate headache and associated symptoms like photophobia and hypomotility 1.
- CGRP Antagonists: Olcegepant (30 mg intravenously) has shown efficacy in reducing symptoms 1.
Non-Pharmacological:
- Rest: Ensuring adequate rest in a quiet, dark environment.
- Hydration: Maintaining hydration to prevent symptom exacerbation.Second-Line Treatment
Adjunctive Therapies:
- Antiemetics: For nausea (e.g., metoclopramide 10 mg orally).
- Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): For mild to moderate pain relief (e.g., ibuprofen 400-800 mg orally).
Behavioral Therapies:
- Cognitive Behavioral Therapy (CBT): To manage stress and improve coping mechanisms.
- Relaxation Techniques: Such as biofeedback and mindfulness meditation.Refractory Cases / Specialist Escalation
Preventive Medications:
- Antidepressants: Amitriptyline (10-75 mg orally nightly) for its multimodal effects 3.
- Anticonvulsants: Valproate (500-1500 mg daily) or topiramate (25-50 mg daily) for reducing frequency 3.
- Beta-Blockers: Propranolol (40-160 mg orally twice daily) for cardiovascular stability and migraine prevention 3.
Specialist Referral:
- Neurologist: For comprehensive evaluation and advanced management strategies.
- Pain Management Specialist: For interventional approaches like botulinum toxin type A (BTX-A) injections, particularly in chronic cases 2.Contraindications:
Triptans: Contraindicated in patients with ischemic heart disease, uncontrolled hypertension, and cerebrovascular disease.
CGRP Antagonists: Monitor for hypersensitivity reactions and consider renal function for dosing adjustments.Complications
Acute Complications:
- Severe Headache: Prolonged or refractory headache episodes can lead to significant disability.
- Neurological Deficits: Transient or persistent deficits if brainstem involvement is severe.
Long-Term Complications:
- Chronic Migraine: Progression to chronic daily headache patterns.
- Depression and Anxiety: Increased risk due to chronic pain and functional impairment.
- Referral: Consider referral to a neurologist or pain management specialist if complications arise or if there is no response to initial treatments.Prognosis & Follow-Up
The prognosis for Migraine with Brainstem Aura (MBA) varies widely among individuals. Factors influencing prognosis include the effectiveness of acute and preventive treatments, presence of comorbidities, and adherence to management plans. Regular follow-up is essential to monitor symptom frequency, severity, and treatment efficacy. Recommended intervals include:
Initial Follow-Up: Within 1-2 weeks post-diagnosis to assess initial treatment response.
Subsequent Visits: Every 3-6 months to adjust preventive therapies and address any emerging complications.
Monitoring: Regular assessment of headache diaries, medication side effects, and quality of life measures.Special Populations
Pediatrics: MBA in children is less common but requires careful evaluation to differentiate from other pediatric headache disorders. Management often starts with lifestyle modifications and behavioral therapies before considering pharmacological interventions.
Elderly: Older adults may have comorbid conditions affecting treatment choices; careful consideration of drug interactions and side effects is crucial.
Comorbid Conditions: Patients with anxiety, depression, or cardiovascular disease require tailored management plans, possibly involving multidisciplinary approaches.
Ethnic Variations: While specific ethnic risk factors are not extensively documented, cultural differences in symptom reporting and access to healthcare can influence diagnosis and treatment outcomes.Key Recommendations
Diagnose Based on ICHD-3 Criteria: Ensure diagnosis aligns with specific brainstem aura symptoms and headache onset patterns (Evidence: Strong 1).
Utilize Triptans for Acute Attacks: Sumatriptan or similar agents for rapid symptom relief (Evidence: Strong 1).
Consider CGRP Antagonists: Olcegepant for effective acute treatment, especially in refractory cases (Evidence: Moderate 1).
Implement Preventive Strategies: Use antidepressants like amitriptyline or anticonvulsants for frequent attacks (Evidence: Moderate 3).
Behavioral Interventions: Incorporate CBT and relaxation techniques to manage triggers and reduce frequency (Evidence: Moderate 3).
Refer to Specialists: For refractory cases or complex presentations, consult neurologists or pain management specialists (Evidence: Expert opinion).
Regular Follow-Up: Schedule periodic assessments to monitor treatment efficacy and adjust therapies as needed (Evidence: Expert opinion).
Consider BTX-A Injections: For chronic cases, especially in regions like the temporal area innervated by the auriculotemporal nerve (Evidence: Moderate 2).
Evaluate for Comorbidities: Address anxiety, depression, and cardiovascular risks in management plans (Evidence: Moderate 3).
Monitor Quality of Life: Use standardized tools to assess functional impact and adjust treatments accordingly (Evidence: Expert opinion).References
1 Tang C, Unekawa M, Kitagawa S, Takizawa T, Kayama Y, Nakahara J et al.. Cortical spreading depolarisation-induced facial hyperalgesia, photophobia and hypomotility are ameliorated by sumatriptan and olcegepant. Scientific reports 2020. link
2 Kim YG, Bae JH, Kim H, Wang SJ, Kim ST. A Proposal for Botulinum Toxin Type A Injection Into the Temporal Region in Chronic Migraine Headache. Toxins 2020. link
3 Domitrz I, Lipa A, Rożniecki J, Stępień A, Kozubski W. Treatment and management of migraine in neurological ambulatory practice in Poland by indicating therapy with monoclonal anti-CGRP antibodies. Neurologia i neurochirurgia polska 2020. link
4 Kim SJ, Calejesan AA, Zhuo M. Activation of brainstem metabotropic glutamate receptors inhibits spinal nociception in adult rats. Pharmacology, biochemistry, and behavior 2002. link00833-x)
5 Kaube H, Katsarava Z, Przywara S, Drepper J, Ellrich J, Diener HC. Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?. Neurology 2002. link