Anatomical and Functional Consequences of Chronic Migraine

Posted on May 09 2025, By: Cerebral Torque

Anatomical and Functional Consequences of Chronic Migraine:

A comprehensive review of the latest evidence on structural and functional brain changes in migraine

Introduction

For many people with migraine, their condition is episodic. Without seeing a neurologist or headache specialist and following an appropriate treatment plan, episodic migraine may progress to chronic migraine [1].

The transformation from episodic to chronic migraine occurs when headache is present on 15 or more days per month for more than 3 months, with migraine features on at least 8 days per month. This chronification occurs in approximately 2.5% of migraine patients annually, while reversion from chronic to episodic migraine happens much less frequently [2].

The goal is to prevent the disability associated with chronic migraine by preventing the transformation from episodic to chronic migraine. Moreover, inadequately treating migraine can result in neurological and possibly structural changes [3].

Why This Matters

Understanding the anatomical and functional consequences of chronic migraine is essential for developing effective prevention and treatment strategies. Recent advances in neuroimaging techniques have revealed complex patterns of brain alterations associated with migraine chronification [4].

Sensory Changes and Central Sensitization

Patients with chronic migraine experience several neurological changes compared to those with episodic migraine. For example, cutaneous allodynia occurs more frequently in people with chronic migraine versus episodic migraine [5].

Cutaneous Allodynia

Cutaneous allodynia refers to the experience of pain from non-painful stimuli that typically do not provoke pain. For example, people with cutaneous allodynia may perceive pain from something as benign as combing their hair. This finding suggests that people with chronic migraine are more susceptible to central sensitization in the nervous system, causing previously non-painful stimuli to trigger painful responses [6].

An increase in nausea is also more common in chronic migraine patients versus episodic migraine, further contributing to disability [7]. Photophobia and phonophobia have also been linked to the development of chronic migraine and are associated with trigeminal hypersensitivity [8].

Hypothalamic and Brain Network Changes

Studies show changes in the hypothalamus in chronic migraine patients compared to those with episodic migraine [9]. As migraine frequency increases (the defining criteria between episodic and chronic), some brain regions demonstrate heightened activation including areas involved in pain reception, sensory processing, and autonomic regulation while other regions important for executive function and emotion processing show decreased coordination between neural networks [10, 11].

Brain Volume Changes

Changes in brain volume occur as migraine attacks increase in frequency and the disease duration increases [12]:

Volume Changes in Chronic Migraine
Increases in Volume Basal ganglia, hippocampus
Decreases in Volume Brainstem, cerebellum
Iron Accumulation Periaqueductal gray matter

There is also accumulation of iron in the periaqueductal gray matter, which can potentially serve as a biomarker for chronic migraine [13].

White Matter Lesions

White matter lesions may be visible on MRI in migraine patients. Studies have found that higher attack frequency and longer disease duration positively correlate with white matter lesions [14]. However, this is an increasingly controversial topic as of 2025 with some studies suggesting no relation. 

Recent Advances in Migraine Neuroimaging

Key Neuroimaging Advances

  • Increased connectivity in pain matrix in chronic migraine patients
  • Functional imaging of premonitory phase providing novel insights
  • Identification of potential biomarkers specific to migraine with aura
  • Advanced 7 Tesla MRI revealing differences in medication overuse headache

Functional Connectivity Changes

Recent neuroimaging studies have provided deeper insights into the functional differences between chronic and episodic migraine. Research has identified increased connectivity in the pain matrix in chronic migraine patients during the interictal period, using advanced resting-state functional MRI techniques [15]. This suggests persistent alterations in pain processing networks even between attacks in chronic migraine patients. A 2024 study by Frimpong-Manson et al. further characterized these neural pathways, demonstrating how third-order neural projections from the thalamus can undergo aberrant stimulation leading to somatic symptoms of migraine [16].

Premonitory Phase Imaging

Advances in human migraine research, particularly the use of functional imaging techniques lacking radiation exposure, have created exciting opportunities to study the premonitory phase using repeated measures imaging designs. These studies have provided novel insights into attack initiation, migraine neurochemistry, and potential therapeutic targets [17]. Recent work by Karsan (2024) has demonstrated that the ability to scan patients repeatedly with non-invasive imaging modalities has allowed for reproducible imaging of the premonitory phase using nitroglycerin as a trigger [18].

Migraine with Aura Biomarkers

Recent fMRI studies have identified potential biomarkers specific to migraine with aura. A January 2025 study showed that the visual cortex in these patients exhibits distinctive activation patterns, reflecting underlying cortical dysfunction that persists beyond acute episodes, potentially due to chronic neuronal dysregulation or hyperexcitability [19]. This research provides further evidence for cortical spreading depression as a basic mechanism underlying migraine with aura.

Medication Overuse/Adaptation Headache Neuroimaging

A 2025 study by Sun et al. using 7 Tesla multimodal MRI found significant neuroimaging differences between chronic migraine patients with and without medication overuse headache [20]. This advanced imaging approach, combining structural, diffusion tensor, and functional imaging, has characterized distinct brain abnormalities in these patient groups and investigated the relationship between acute analgesic use frequency and these changes. The study demonstrated that medication overuse leads to specific neurobiological alterations that differ from those seen in chronic migraine alone.

Choroid Plexus Volume and Association with Migraine (2025)

What is the Choroid Plexus?

The choroid plexus is located inside the ventricular system of the brain. It forms the blood-cerebrospinal fluid barrier and plays vital roles in maintaining brain homeostasis, including cerebrospinal fluid production and clearance [21]. Recent research has identified the choroid plexus as an important neuroimmunological interface involved in various neurological conditions [22].

A 2025 study by Xiong et al. has identified the choroid plexus as a significant structure in migraine pathophysiology [23]. The research recruited 65 participants (18 with episodic migraine, 16 with chronic migraine, and 31 healthy controls) who underwent brain MRI examinations. The research team used FreeSurfer (Version 7.4.1) software to automatically segment and measure the choroid plexus volume.

Episodic Migraine
Decreased CP/LV ratio compared to controls
Chronic Migraine
Increased CP/LV ratio as disease duration increases
100%
Sensitivity
The right-side CP/LV ratio distinguished episodic migraine from controls with high sensitivity

Key Findings on Choroid Plexus Volume

  • Differential changes in choroid plexus volume: Episodic migraine patients showed decreased choroid plexus to lateral ventricle (CP/LV) ratio, while chronic migraine patients exhibited increased CP/LV ratio compared to controls [23].
  • Diagnostic potential: The right-side CP/LV ratio could differentiate episodic migraine from controls with area under the ROC curve (AUC) of 0.696 (95% CI: 0.550-0.818), sensitivity of 100%, and specificity of 46.8%. The diagnostic efficacy was even higher in distinguishing chronic migraine from episodic migraine with AUC of 0.715 (95% CI: 0.536-0.856) [23].
  • Correlation with clinical features: Patients with migraine demonstrated increased anxiety, depression, heavier headache burden, and impaired cognitive abilities compared to controls [23].
  • Dynamic alterations: The findings suggest dynamic changes in lateral ventricular choroid plexus volume during migraine pathogenesis, with the normalized CP/LV ratio associated with different migraine subtypes [24].
This research suggests that normalized CP/LV measurements could potentially serve as an imaging biomarker for migraine diagnosis and classification. The changes in choroid plexus volume may reflect underlying mechanisms of peripheral-central interaction in migraine, which has been hypothesized but lacked direct evidence until now [23].

Migraine Comorbidities

Besides neurological and anatomical changes, migraine also comes with comorbidities [25]. Increased central sensitization and activation of the trigeminovascular pathway due to migraine play roles in the pathogenesis of other pain syndromes as well.

Frequent migraine attacks result in ongoing inflammation and activation of certain nerve fibers in the trigeminal system. This leads to the release of more CGRP and other neuropeptides that promote inflammation and sensitization of trigeminal nerves [26]. This sensitization leads to changes in pain processing networks in the brain, which in turn leads to migraine chronification and other comorbidities.

Major Comorbidities with Chronic Migraine

  • Anxiety and depression
  • Sleep disorders
  • Other chronic pain syndromes
  • Cognitive dysfunction
  • Vestibular symptoms

Conclusion

Understanding the anatomical and functional consequences of chronic migraine is essential for developing effective prevention and treatment strategies. Recent advances in neuroimaging techniques have revealed complex patterns of brain alterations associated with migraine chronification [27].

The identification of the choroid plexus as a structure involved in migraine pathophysiology opens new avenues for research and potential therapeutic targets [28]. The evidence of dynamic alterations in choroid plexus volume associated with different migraine subtypes may eventually lead to improved diagnostic criteria and personalized treatment approaches.

Emerging therapeutic research targeting various pathways, including CGRP, PACAP, and other potential molecular targets, shows promise for migraine prevention and treatment [29]. According to a 2024 publication in The Lancet Neurology, early intervention with targeted therapies may lead to better outcomes for patients [30].

It is crucial to stop the progression from episodic to chronic migraine, as this transformation is associated with significant disability, neuroanatomical changes, and functional alterations. Effective management requires evidence-based approaches rather than unproven "hacks" and misinformation.

References

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  2. Manack A, Buse DC, Serrano D, et al. Rates, predictors, and consequences of remission from chronic migraine to episodic migraine. Neurology. 2011;76(8):711-718.
  3. Dodick DW. Migraine. Lancet. 2018;391(10127):1315-1330.
  4. Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(Pt 7):1987-1993.
  5. Louter MA, Bosker JE, van Oosterhout WP, et al. Cutaneous allodynia as a predictor of migraine chronification. Brain. 2013;136(Pt 11):3489-3496.
  6. Burstein R, Yarnitsky D, Goor-Aryeh I, et al. An association between migraine and cutaneous allodynia. Ann Neurol. 2000;47(5):614-624.
  7. Kelman L. The triggers or precipitants of the acute migraine attack. Cephalalgia. 2007;27(5):394-402.
  8. Noseda R, Copenhagen D, Burstein R. Current understanding of photophobia, visual networks and headaches. Cephalalgia. 2019;39(13):1623-1634.
  9. Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: Evidence from high-resolution fMRI. Neurology. 2017;88(21):2011-2016.
  10. Schwedt TJ, Chiang CC, Chong CD, et al. Functional MRI of migraine. Lancet Neurol. 2015;14(1):81-91.
  11. Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol. 2011;70(5):838-845.
  12. Kim JH, Suh SI, Seol HY, et al. Regional grey matter changes in patients with migraine: a voxel-based morphometry study. Cephalalgia. 2008;28(6):598-604.
  13. Welch KM, Nagesh V, Aurora SK, Gelman N. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Headache. 2001;41(7):629-637.
  14. Kruit MC, van Buchem MA, Hofman PA, et al. Migraine as a risk factor for subclinical brain lesions. JAMA. 2004;291(4):427-434.
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  19. Neurology International. fMRI Insights into Visual Cortex Dysfunction as a Biomarker for Migraine with Aura. Neurol Int. 2025;17(2):15.
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Summary Table

This table summarizes the key findings from current research on how chronic migraine affects brain structure and function, recent neuroimaging advances, and associated comorbidities.

Category Key Findings
Definition & Chronification Chronic migraine defined as:
  • Headache on ≥15 days/month for >3 months
  • Migraine features on ≥8 days/month
Progression rates:
  • ~2.5% of episodic migraine patients progress to chronic annually
  • Reversion from chronic to episodic is less common
Without proper treatment, neurological and structural changes may occur
Sensory Changes
  • Cutaneous allodynia: Pain from normally non-painful stimuli (e.g., combing hair), more common in chronic migraine
  • Increased nausea: More prevalent in chronic vs. episodic migraine
  • Photophobia and phonophobia: Linked to chronic migraine development and trigeminal hypersensitivity
Indicates central sensitization in the nervous system
Brain Volume Changes As migraine frequency and disease duration increase:
  • Volume increases: Basal ganglia, hippocampus
  • Volume decreases: Brainstem, cerebellum
  • Iron accumulation: Periaqueductal gray matter (potential biomarker)
  • White matter lesions: Correlation with attack frequency (though increasingly controversial in 2025)
Neural Network Changes
  • Hypothalamic changes: Altered in chronic vs. episodic migraine
  • Heightened activation: In pain reception, sensory processing, and autonomic regulation areas
  • Decreased coordination: Between networks important for executive function and emotion processing
  • Increased connectivity: In pain matrix during interictal periods in chronic migraine
Recent Neuroimaging Advances (2024-2025)
  • Premonitory phase imaging: Non-invasive techniques providing insights into attack initiation
  • Migraine with aura biomarkers: Distinctive visual cortex activation patterns
  • Medication overuse headache: 7 Tesla MRI showing distinct brain abnormalities
  • Choroid plexus volume: Newly identified as significant in migraine pathophysiology
Choroid Plexus Findings (2025) Differential changes in choroid plexus volume:
  • Episodic migraine: Decreased choroid plexus to lateral ventricle (CP/LV) ratio
  • Chronic migraine: Increased CP/LV ratio compared to controls
  • Diagnostic potential: Right-side CP/LV ratio differentiated episodic migraine from controls (100% sensitivity)
  • Dynamic alterations: Suggesting CP/LV measurements could serve as imaging biomarkers
Common Comorbidities Frequent migraine leads to ongoing inflammation and trigeminovascular activation:
  • Anxiety and depression
  • Sleep disorders
  • Other chronic pain syndromes
  • Cognitive dysfunction
  • Vestibular symptoms
Sensitization leads to changes in pain processing networks