BICTEL/e - ULg
Serveur institutionnel des thèses de doctorat

• Cluster headache/algie vasculaire de la face
• pain/douleur
• neurostimulation
• drug-resistant/réfractaire

Cluster headache is a primary headache disorder belonging to the so-called

“trigeminal autonomic cephalalgias”. Its prevalence is close to that of multiple sclerosis and it affects more males than females. Attacks are characterized by severe unilateral periorbital pain associated with ipsilateral autonomic signs. The classical, most frequent form is

episodic with a circannual periodicity with bouts of attacks alternating with periods of complete remission. Unfortunately, 10% of patients have or develop a chronic form with time,

i.e. they have no remissions lasting at least 1 month (CCH). Among these chronic patients,some become resistant to prophylactic drugs and are considered as refractory (rCCH). They

are severely disabled and often suicidal. Various alternative, mostly destructive, procedures have been tempted to relieve these patients over the last decades, targeting the trigeminal nerve or the parasympathetic outflow, but none provided sustained relief, or some relief was achieved at the expense of permanent neurological deficits.

New hope arose ten years ago when spectacular results were obtained in a rCCH patient treated by deep hypothalamic neurostimulation. These results were confirmed by a

pilot study of 5 rCCH patients performed at our Research Centre. However, this technique is invasive and not riskless, as it may cause cerebral haemorrhage. This is the reason why we

turned to a less hazardous technique, occipital nerve stimulation (ONS). We studied its therapeutic effects and tolerance over the middle and the long tem, as well as its mode of

action.

Between 2005 and 2009 we enrolled in total 15 patients suffering from rCCH for unilateral implantation of a paddle style lead with 4 electrode plots (Medtronic 3587A Resume II) on the side of the headache. Results in the first 8 patients were summarized after a mean follow-up of 15.1 months. Two patients were pain-free, 3 had a reduction of attack frequency by 90%, 2 by 40%, while another patient did not tolerate the paraesthesias induced by ONS and switched the stimulator off. No major side effects were reported. Hence,

we included 7 additional patients. Their long-term follow-up (up to 5 years ONS) confirms the

excellent efficacy and tolerance of ONS: 11 patients have a ≥ 90% improvement in attack frequency and 60% have pain-free periods of several months. ONS has no significant effect

on pain intensity of remaining attacks. Clinical peculiarities associated with the treatment are non painful autonomic attacks on the cluster side, and transient switching of attacks to the

opposite side. The most frequent side effects were battery depletion and replacement (64%) as well as immediate or delayed local infections of the implanted material (20%). Only 29%

of patients were able to reduce their preventive drug treatment.

We studied the mechanisms of action of ONS in two ways: first with

neurophysiological recordings (algometry and nociception-specific blink reflex), and second

with functional neuroimaging (positon emission tomography with 18-FDG). These studies show for the first time that the posterior hypothalamus, known to be hyperactive during attacks, is hypermetabolic between attacks in rCCH patients. Moreover, they suggest that

ONS exerts its benefit through slow central neuromodulation of the “pain neuromatrix”, and via activation of the perigenual anterior cingulate gyrus that is involved in a top-down

opioidergic pain control system. ONS has no detectable antinociceptive effect on spinal trigeminal nucleus and does not modify the hypothalamic hypermetabolism, which probably

explains the recurrence of attacks within days after stimulator arrest.

To summarize, we have demonstrated in an open, non-controlled but prospective

long term study the therapeutic efficacy and good tolerance of ONS as a preventive treatment of rCCH. This neuromodulation method has the advantage of being minimally

invasive, riskless, and devoid of serious side effects. Our neurophysiological and neuroimaging studies of its mechanisms of action show that ONS acts on pain control

systems, but not on the posterior hypothalamus that is supposed to be more causally related to the occurrence of cluster attacks and autonomic symptoms.

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