Acetazolamide for the prophylaxis of migraine in CADASIL: a preliminary experience

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by NOTCH3 mutations. It is characterized by migraine, with or without aura, ischemic events, psychiatric and cognitive disturbances. There is no approved treatment for migraine prophylaxis in CADASIL, but acetazolamide has been anecdotally reported to be effective. We retrospectively reviewed our database of patients with a genetic diagnosis of CADASIL to identify how many of them were treated with acetazolamide for the prophylaxis of migraine. The efficacy and the tolerability of this treatment were checked looking at the clinic reports. Acetazolamide was prescribed in seven patients; the mean duration of treatment was 6 months, and the daily dose ranged from 125 to 500 mg. Three patients had a total and sustained remission, while in two patients a reduction in attacks and an improvement of the headache intensity were recorded. In one of these, acetazolamide was deliberately taken only during the migraine attack and the beneficial effect started 1 h after administration. In two patients, the drug did not produce any beneficial effect. Mild side effects were recorded in two patients. Our preliminary experience expands previous reports and confirms the possible efficacy of acetazolamide in CADASIL migraine. Based on these data, a randomized controlled trial seems worthy to be carried out to test the efficacy and safety of this drug.

CADASIL: Migraine, Encephalopathy, Stroke and Their Inter-Relationships

“…[ 5 – 8 ] Furthermore, little is known about how it responds to therapy and whether the management of migraine in CADASIL should differ from that of migraine in the general population. [ 9 – 12 ] Epidemiological studies have demonstrated that migraine, in particular migraine with aura, is an independent risk factor for stroke in the general population. [ 13 – 16 ] However, whether the presence of migraine with aura in CADASIL is predictive of an earlier onset of stroke and a more severe phenotype is unknown.…”

Acute Postpartum Headache

“…For migraine with aura, conventional prophylactic medications are recommended if attack frequency warrants treatment. Acetazolamide has been anecdotally reported to be effective in the prophylaxis of migraine in CADASIL, but randomized, controlled trials are lacking 57‐59. Acetazolamide has also been suggested to improve overall cerebral hemodynamics in CADASIL, perhaps suggesting a protective effect, but this has also not been proven in controlled trials .…”

“…Acetazolamide has been anecdotally reported to be effective in the prophylaxis of migraine in CADASIL, but randomized, controlled trials are lacking. [57][58][59] Acetazolamide has also been suggested to improve overall cerebral hemodynamics in CADASIL, perhaps suggesting a protective effect, but this has also not been proven in controlled trials. 60,61 For acute treatment of migraine attacks, triptans and ergot derivatives should generally be avoided due to the high risk of stroke in these patients, and simple analgesics and non-steroidal anti-inflammatory drugs are preferred.…”

Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

“…Prophylactic migraine strategies include good lifestyle and drugs normally used for migraine patients, with caution for amitriptyline, beta-blockers, flunarizine, and topiramate since they may worsen mood and cognitive symptoms (Finocchi et al, 2010). One study demonstrated a beneficial effect of acetazolamide on migraine (Donnini et al, 2012). CADASIL patients with migraine seem to have higher blood homocysteine levels, and B vitamin supplementation lowering homocysteine was seen to decrease migraine severity and frequency (Bousser and Tournier-Lasserve, 2001).…”