CADASIL and migraine: A narrative review

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.