Migraine-Like Headache in Bacterial Meningitis

Abstract

The effect of sumatriptan has not been previously described in the treatment of the headache of meningitis, although this headache has similarities to migraine. This study presents the clinical features of two patients who had fulminant bacterial meningitis with migraine-like headache and who experienced no improvement in headache intensity after administration of sumatriptan 6 mg s.c. On these grounds the lack of response of this type of headache to sumatriptan is discussed.

Introduction

Headache is one of the most common symptoms of bacterial meningitis. According to the diagnostic criteria of the International Headache Society (HIS) this type of headache is classified under 7.3, ‘Headache associated with intracranial infection’ (1). The clinical features are described as frontal or generalized throbbing headache, usually increasing in severity over minutes (2). Accompanying symptoms such as vomiting, phonophobia and photophobia are frequent. There are possibly some physiopathological aspects in common between this type of headache and migraine. The main causes are meningeal irritation with direct stimulation of the sensory nerve endings at the meningeal vessels (3), neurogenic inflammation, increased intracranial pressure and fever. Moskowitz argued that the blockade of neuronal transmission and neurogenic inflammatory response provide a mechanism by which sumatriptan alleviates migraine headache (4). In both case reports described in this study, sumatriptan was found to be ineffective in migraine-like headaches due to bacterial meningitis. As a consequence the above-cited theory needs reconsideration and will be discussed in the following.

Case reports

A 27-year-old man developed a temperature (37.9°C) together with nausea, moderate neck pain and right-sided headache. He had a migraine history of about 10 years, with a frequency of two to three attacks per month which were usually well controlled with oral sumatriptan. As the symptoms he experienced on that occasion were similar to those of previous migraine attacks, he took 100 mg oral sumatriptan at home. However, the headache and the fever persisted and the patient visited our pain clinic. The neurological status revealed mild meningeal symptoms, otherwise there were no abnormalities. In order to exclude other symptomatic headaches a cerebral magnetic resonance imaging (MRI) was performed which showed no intracerebral structural lesions. The EEG revealed focal slowing in the right hemisphere. Within 2 h a rise in temperature to 39.2°C occurred. The patient was somnolent with a throbbing headache, photophobia and phonophobia, vomiting and aggravation of his symptoms when walking around. After lumbar puncture the cerebrospinal fluid (CSF) showed pleocytosis of 28 500 cells/mm³, elevated levels of total protein and immunoglobulins. The Gram-stained smear of the CSF showed Gram-positive cocci identified as β-haemolytic streptococci. After exclusion of intracranial vasospasm by transcranial Doppler sonography, 6 mg of sumatriptan were administered subcutaneously without any effect. Therefore a combination of metamizole 2 g and metoclopramide 20 mg was given by infusion. The patient reported moderate pain relief within the first hour after administration, the effect of which lasted for more than half a day. The next day the patient reported a migraine-like headache comparable to that of the previous days with similar concomitant symptoms. Once again 6 mg of sumatriptan were given by the subcutaneous route, but without any response. Thereupon headache treatment was started using metoclopramide and metamizole twice daily. Two days after the onset of the illness a left-sided hemiparesis occurred. The subsequent spiral computed tomography (CT) angiography revealed a thrombosis of the left sigmoid sinus. Heparin was initiated and the acute neurological signs regressed within 4 days.

The second case was a 19-year-old female migraine patient, receiving sumatriptan s.c. for acute migraine treatment. She developed a temperature (40.2°C), somnolence and a diffuse moderate, pulsating headache predominantly on the right. The patient was unable to move and was confined to bed. In the afternoon the headache worsened and was accompanied by vomiting, photophobia and phonophobia. The patient presented with typical meningeal signs at the pain clinic. Because of the migraine-like headache she received 6 mg sumatriptan subcutaneously, after intracranial vasospasm had been excluded. However, this medication did not have any effect on her headache.

The blood sample obtained revealed a slight deviation to the left and the level of C-reactive protein was 414 mg/l. The lumbar puncture showed 25 000 cells/mm³. As the quick test for meningitis was positive for meningococcus, therapy with penicillin and rocephine was started. Because of a persisting headache and the lack of effect of a second dose of sumatriptan 6 mg s.c., metamizole was given resulting in pain relief. The patient recovered within 1 week.

Discussion

Sumatriptan proved to be ineffective in these two cases of bacterial meningitis described above. Based on a neuronal mechanism it can be hypothesized that sumatriptan inhibits neurogenic inflammation via prejunctional mechanisms. Decreasing neurotransmitter release, which abolishes the mast cell, as well as platelet and endothelial cell changes reduce neurogenic inflammation in the meningeal arteries. Although Moskowitz's trigeminovascular pathway studies were of great importance in the development of a suitable model to test potential 5-HT 1B/1D agonists and other agents, the observations of these cases do not stand in line with Moskowitz's theory.

A series of drugs such as antisubstance P agents and others has been clearly shown to inhibit protein extravasation much more efficiently than the triptans in the Moskowitz model, but to be of absolutely no benefit when tested in migraine (5). This observation plus the findings of Weiller (6) regarding the brain stem activity in migraine have cast considerable doubt on the older theory.

Another speculation could be that the mechanism of headache after meningitis does not closely resemble theories of migraine. It can be hypothesized that the inflammation in meningitis is not neurogenic and therefore a presynaptic inhibition of this mechanism will not cure headache. This may also speak in favour of vasodilatation as a cause of migraine but not meningitis headache.

A third possibility, that the two described patients were non-responders to sumatriptan, can be reasonably discarded, since they were both migraine sufferers who had previously responded to this drug.