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CADASIL and migraine: A narrative review
Michael K Liem1, Saskia A J Lesnik Oberstein, Jeroen van der Grond
1Leiden University Medical Center, Netherlands. m.k.liem@lumc.nl
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), linked to NOTCH3 mutations, shows a higher prevalence of migraine with aura. This review explores how CADASIL may illuminate migraine pathophysiology.
Area of Science:
- Neurology
- Genetics
- Vascular Neurology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by NOTCH3 gene mutations.
- Clinical features include recurrent stroke, cognitive decline, psychiatric issues, and migraine, with a notably higher prevalence of migraine with aura in CADASIL patients compared to the general population.
Purpose of the Study:
- To review existing literature on migraine in CADASIL.
- To investigate potential pathophysiological mechanisms underlying the increased prevalence of migraine with aura in CADASIL.
- To explore how studying CADASIL can enhance understanding of general migraine pathophysiology.
Main Methods:
- This is a narrative review.
- Literature search on migraine and CADASIL was conducted.
- Focus on studies investigating the link between NOTCH3 mutations, cortical spreading depression (CSD), and migraine aura.
Main Results:
- Migraine is more common in CADASIL patients, with a significantly higher proportion experiencing migraine with aura.
- The exact mechanism for increased migraine aura prevalence in CADASIL remains unclear.
- Hypothesized mechanisms include altered susceptibility or expression of cortical spreading depression (CSD), potential involvement of brainstem migraine areas, or the NOTCH3 mutation acting as a migraine aura susceptibility gene.
Conclusions:
- CADASIL presents a unique model for studying migraine with aura.
- Further research into CADASIL may reveal novel insights into the genetic and physiological underpinnings of migraine.
- Understanding the role of NOTCH3 in migraine pathophysiology could lead to new therapeutic targets.
Abstract:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine. The prevalence of migraine in CADASIL is slightly higher than in the general population, and the proportion of migraine with aura is much higher. The pathophysiological mechanism that leads to increased aura prevalence in CADASIL is unknown. Possible mechanisms of the excess of migraine with aura are an increased susceptibility to cortical spreading depression (CSD) or a different expression of CSD. It is also possible that the brainstem migraine area is involved in CADASIL. Last, it is possible that the NOTCH3 mutation acts as a migraine aura susceptibility gene by itself. In this narrative review we summarize the literature about migraine in CADASIL, with a special focus on what CADASIL might teach us about the pathophysiology of migraine.
