Transcranial magnetic stimulation reveals cortical hyperexcitability in episodic cluster headache

Evidence has been provided of involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation (TMS). In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (i.e. motor threshold, MT; input-output curves, I-O curves; cortical silent period, CSP) and paired-pulse TMS (i.e. intracortical facilitation, ICF; intracortical inhibition, SICI) in both hemispheres. Thirteen patients were evaluated outside bout, while the remaining 12 patients were inside bout. Our results showed increased slope of the I-O curves after stimulation of both hemispheres in patients outside bout, and in the hemisphere contralateral to the headache side in patients inside bout. Increased ICF was observed in the hemisphere ipsilateral to the headache side in patients evaluated both outside and inside bout; reduced SICI was observed in patients inside bout ipsilaterally to the side of pain. In conclusion, we provide evidence of increased cortical excitability in episodic CH both outside and inside bout, especially in the hemisphere ipsilateral to the side of headache attacks. Our results suggest that an abnormal regulation of cortical excitability could be involved in the pathophysiology of CH.