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High dose intravenous methylprednisolone in cluster headache
  1. Department of Neurosciences, Sect Neuropsichiatria Inf, University of Cagliari, Italy
  1. Professor Carlo Cianchetti, Dpt Neuroscienze, Cl Neuropsichiatria Inf, via Ospedale 119, 09124 Cagliari, Italy. Fax 0039 70 669591.

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Bouts of cluster headache may be resistant to all the drugs usually effective, such as typical migraine preventing drugs, lithium, carbamazepine, valproate, and corticosteroids. Corticosteroids have been commonly used in cycles of 10–15 intravenous daily infusions of 50–100 mg prednisone. During a severe bout in a patient resistant to all treatments, we have tried high dose (500 to 1000 mg/day intravenously) methylprednisolone administration: single doses were found to be effective in blocking headache attacks for several days.

A 53 year old man began to have cluster headache at the age of 35. For several years he had about one cluster every two years, easily controlled by one or more of the commonly used drugs. In the past years, however, the clusters became increasingly resistant to all treatment. When aged 51 he had a cluster lasting more than 10 months, completely insensitive to the following drugs at the maximal doses he tolerated: 360 mg/day verapamil, 900 mg/day lithium (plasma concentrations 0.8–0.9 mEq/l), 4.2 mg/day methisergide, 20 mg/day flunarizine, 400 mg/day carbamazepine, 100 mg/day oral prednisone, and 300 mg/day indomethacin. After more than one year free from attacks, they reappeared with severe intensity, one to four a day, mainly during the night. The previously used drugs, as well as infusions of 100 mg/day prednisone for two weeks and hyperbaric O2, alone and in association, were without effect. Relief was obtained only from sumatriptam at the onset of the attacks. After three months of ineffective attempts, we decided to administer 500 mg methylprednisolone intravenously (three hour infusion in saline) (figure, first slim arrow). Attacks stopped the same day of the infusion and the benefical effect persisted, a single attack only reappearing six days later. Again 500 mg methylprednisolone was administered, giving relief for five days. We continued a schedule of treatment based on a single 500 mg dose of methylprednisolone (figure, slim arrows) at the reappearance of a consistent attack, increasing the dose to 1000 mg (figure, thick arrow) from October. Methylprednisolone administration was associated with the H2 receptor antagonist ranitidine. Concomitant treatments with (figure) 360 mg/day verapamil, 900 mg/day lithium carbonate, up to 200 mg/day lamotrigine, 300 mg/day indomethacin, 4.2 mg/day methisergide, and 1000 mg/day valproate did not prolong the periods free from attacks. Two successive methylprednisolone administrations at only three day intervals did not prolong the benefical effect, which appeared to reduce its duration with time. Fortunately, the cluster vanished at the beginning of the 9th month from onset. No secondary effects of methylprednisolone treatment were seen.

Record of attacks and treatment schedule. Attacks stopped immediately and for several days after intravenous methylprednisolone infusion at a dose of 500 mg during the first two months and 1000 mg thereafter. Concomitant treatments (doses reported in the text) did not seem to modify the occurrence of the attacks.

In the past 10 years, the use of high dose steroids, mainly 500–1000 mg/day methylprednisolone intravenously for three to10 days, has been proved to be effective in some neurological (for example, multiple sclerosis) and internal diseases of autoimmune origin. In these diseases the treatment has been found well tolerated, more effective than prolonged steroid therapy at lower doses, and devoid of significant adverse effects.

No role of the immune system has been so far proved in cluster headache. However, cycles of steroid therapy at medium doses have long been known to be among the most effective treatments.1-3The only suggestion of a role for the immune system came from Martelletti and Giacovazzo,4 who found an association of the HLA B21/DR5 antigen with responsiveness to prednisone therapy (our patient has HLA B7 B49 Dr2 Dr4 DR 53). Alternatively, steroids might suppress the release of vasoactive inflammatory agents—for example, stabilising mast cells.5

The present case suggests a possible benefical effect of high dose intravenous steroids in cases of cluster headache resistant to usual steroid doses and to other drugs. In our opinion the possibility of a benefical effect can be tested with a single administration of 500–1000 mg methylprednisolone, which is almost devoid of risk.