Table 3

Pharmacological treatments in hemiplegic migraine

Drug	Mechanism of action	Administration	Clinical outcome	Level of evidence
Acute management of aura
Verapamil	Calcium antagonism on L-type calcium channel, blocking calcium influx and reducing vasoconstriction. Less prominent effects on P/Q calcium channels.	Intravenous verapamil (5 mg over 5 min), followed by an oral maintenance dose of 120 mg/day.	Significative reduction of headache, but not completely resolution of hemiplegia, especially in patients with CACNA1A mutations.	Low; case reports and small studies (Yu et al94).
Ketamine	NMDA glutamate receptors antagonism.	Intranasal administration.	May be beneficial in about 45% of cases.	Low; a study on 11 patients with FHM (Kaube et al82).
Triptans	5-HT_1B/1D agonism.	Oral or subcutaneous.	In a study on 76 patients with HM, 62% reported a good or excellent response with moderate adverse events (chest pain, nausea and fatigue),	Debated; the evidence comes from a study of 76 patients with HM (Artto et al91).
Corticosteroid pulses and hypertonic solution	Steroids: indirect inhibition of the activity of voltage-dependent calcium channels; reduction of CSD. Hypertonic solution: unknown.	Intravenous dexamethasone 0.5 mg/kg/day in three pulses/day for 3 days followed by gradual oral tapering and hypertonic solution at 3% 1.5 mL/kg/hour, maintaining sodium between 145 and 155 mEq/L. In another report, a scheme with a 5-day treatment of 100 mg/day methylprednisolone was used.	Rapid reduction in severity and duration of acute attacks in the presence of encephalopathy and cerebral oedema in patients with CACNA1A mutations.	Low; single reports (Sánchez-Albisua et al89; García Segarra et al100; Camia et al97).
Prochlorperazine and magnesium sulfate	Dopamine D2 receptors antagonism. Blockage of CSD due to magnesium.	Intravenous.	Intravenous prochlorperazine and magnesium sulfate seemed to resolve prolonged migrainous aura.	Putative; little evidence based on a single report (Rozen et al88).
Naloxone	Opiate-antagonism (possible role for endorphins).	0.4 mg of intravenous naloxone.	Aborted neurological sequelae in two patients with SHM.	Putative; little evidence based on a single report (Centonze et al98).
Furosemide	Possible cessation of CSD.	Intravenous.	Seemed to resolve prolonged migrainous aura in two patients.	Putative; little evidence based on a single report (Rozen et al87).
Prophylactic treatment
Verapamil	Calcium antagonism on L-type calcium channel, blocking calcium influx and reducing vasoconstriction. Less prominent effects on P/Q calcium channels.	Oral verapamil (120 mg twice or three times in a day).	May be effective in reducing the burden of attacks in HM.	Low; case reports and small studies (Lai et al83; Razavi et al86; Yu et al95; Lastimosa et al85; Hsu et al102; Rispoli et al21).
Acetazolamide	Unknown; a local pH change around the P/Q Ca²⁺ channel may result in improved channel functioning.	Oral 250–500 mg twice a day.	May be effective in reducing the burden of attacks in HM and nystagmus, especially in patients with CACNA1A mutations (EA2, SCA6) and CADASIL.	Low; little evidence based on case reports and case series (Athwal et al96; Battistini et al19; Striano et al103; Suzuki et al18).
Flunarizine	Non-selective calcium ion channel and dopamine receptor antagonism. 5-HT and antihistamine receptors antagonism.	Oral 10 mg/day.	Generally effective and well-tolerated, except for low rate of adverse effects (tiredness, mood changes and weight gain).	Low; single reports (Tobita et al90; Karsan et al81).
Lamotrigine	Blockage of the sodium channels, decreasing the neuronal release of glutamate.	Oral.	May be beneficial.	Low; a study with eight patients with motor aura, a case report (Lampl et al84; Camia et al97).
Propranolol	Unknown.	Oral 10 mg 3–4 times a day and maintenance from 1.5 to 3.0 mg/kg/day.	Effective in three patients with longer symptom-free intervals.	Low; single report (Lai et al83)
Memantine and dextromethorphan	NMDA antagonism.	Oral.	Significant improvement of behavioural, cognitive and cerebellar symptoms in a patient with ATP1A2 mutation.	Putative; single report (Ueda et al92).
Telcagepant	CGRP receptor antagonism.	Oral.	May be beneficial.	Putative (Ho et al101).
Onabotulinumtoxin A	Unknown.	Subcutaneous.	Reduction of aura frequency and severity.	Putative; single report (Chen et al99; Young et al93).
Topiramate	Unknown.	Oral.	Worsening of symptoms in a single HM case: dysphasia, disorientation, and prolonged severe right-sided weakness complicating a migraine attack lasting for about 4 days.	Putative; single report (Striano et al103).

CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CGRP, calcitonin gene-related peptide; CSD, cortical spreading depression; HM, hemiplegic migraine; 5-HT, 5-hydroxy tryptamine; NMDA, N-methyl-D-aspartate.