Sustained effectiveness of occipital nerve stimulation in drug-resistant chronic cluster headache.

BACKGROUND: Drug-resistant chronic cluster headache (drCCH) is a devastating condition for which various invasive therapeutic procedures have been tempted without any satisfactory effect. Recent studies suggest that occipital nerve stimulation (ONS) could be an efficient preventive treatment of drCCH. OBJECTIVE: We conducted a prospective pilot trial of ONS in 8 subjects suffering from drCCH with encouraging results at 15 months. However, studies on a larger population with a longest follow-up were warranted. METHODS: We recruited 15 patients with drCCH according to the previously published criteria of intractability. They were implanted with suboccipital stimulators on the side of their headache. Long-term follow-up was achieved by questionnaires administered during a headache consultation and/or by phone interviews. RESULTS: Mean follow-up time post surgery is 36.82 months (range 11-64 months). One patient had an immediate post-operative infection of the material. Among the 14 remaining patients, 11 (i.e., ∼80%) have at least a 90% improvement with 60% becoming pain-free for prolonged periods. Two patients did not respond or described mild improvement. Intensity of residual attacks is not modified by ONS. Four patients (29%) were able to reduce their prophylaxis. The major technical problems were battery depletion due to the use of high current intensities (N = 9/14, 64%) and immediate or delayed material infection (N = 3/15, 20%). Significant electrode migration was only seen in 1 patient. Clinical peculiarities during the ONS follow-up period were side shift with infrequent contralateral attacks (N = 5/14, 36%), and/or isolated ipsilateral autonomic attacks without pain (N = 5/14, 36%). Two patients found ONS-related paresthesias unbearable: one had his stimulator removed, and the other switched it off although he was objectively ameliorated. Subjectively, 9 patients are very satisfied by ONS and 3 patients moderately satisfied. Effective stimulation parameters varied between patients. CONCLUSIONS: Our long-term follow-up confirms the efficacy of ONS in drCCH, which remains a safe and well-tolerated technique. The occurrence of contralateral attacks and isolated autonomic attacks in nearly 50% of ONS responders may have therapeutic and pathophysiological implications.

Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study.

BACKGROUND: Occipital nerve stimulation (ONS) has raised new hope for drug-resistant chronic cluster headache (drCCH), a devastating condition. However its mode of action remains elusive. Since the long delay to meaningful effect suggests that ONS induces slow neuromodulation, we have searched for changes in central pain-control areas using metabolic neuroimaging. METHODS: Ten drCCH patients underwent an 18FDG-PET scan after ONS, at delays varying between 0 and 30 months. All were scanned with ongoing ONS (ON) and with the stimulator switched OFF. RESULTS: After 6-30 months of ONS, 3 patients were pain free and 4 had a ≥ 90% reduction of attack frequency (responders). In all patients compared to controls, several areas of the pain matrix showed hypermetabolism: ipsilateral hypothalamus, midbrain and ipsilateral lower pons. All normalized after ONS, except for the hypothalamus. Switching the stimulator ON or OFF had little influence on brain glucose metabolism. The perigenual anterior cingulate cortex (PACC) was hyperactive in ONS responders compared to non-responders. CONCLUSIONS: Metabolic normalization in the pain neuromatrix and lack of short-term changes induced by the stimulation might support the hypothesis that ONS acts in drCCH through slow neuromodulatory processes. Selective activation in responders of PACC, a pivotal structure in the endogenous opioid system, suggests that ONS could restore balance within dysfunctioning pain control centres. That ONS is nothing but a symptomatic treatment might be illustrated by the persistent hypothalamic hypermetabolism, which could explain why autonomic attacks may persist despite pain relief and why cluster attacks recur shortly after stimulator arrest. PET studies on larger samples are warranted to confirm these first results.

Intensity dependence of auditory evoked potentials during light interference in migraine.

Migraine patients show interictally a strong intensity dependence of auditory evoked cortical potentials (IDAP) and a lack of habituation of evoked potentials. Photic drive on high-frequency flash stimulation is another well-known interictal feature in migraineurs, associated with alpha-rhythm hyper-synchronisation. We compared therefore the influence of light stimulation on IDAP in healthy volunteers (HV) and migraine patients. A continuous flash stimulation was delivered during the recording of auditory evoked potentials at suprathreshold increasing stimulation intensities. IDAP was measured as the amplitude/stimulus intensity function (ASF) slope. In HV, the ASF slope decreased during flash stimulation, whereas, on average, there was no significant change in migraineurs. A closer analysis of migraineurs disclosed two subgroups of patients with no detectable clinical differences: one, the largest, in which the ASF slope was normal at baseline, but increased during light stimulation, the other with an increased ASF slope at rest and a decrease during light interference. Visual sensory overload is able to increase IDAP in the majority of migraineurs, which contrasts with HV. We hypothesise that this could be due to hyper-synchronisation of the alpha rhythm because of photic drive and possibly thalamo-cortical dysfunction. A minority of migraineurs have, like HV, an IDAP reduction during light interference. They are, however, characterised, unlike most HV, by a high IDAP at baseline. Besides underscoring the pathophysiological heterogeneity of migraine, these results suggest that light interference might improve the phenotyping of migraine patients who have a normal IDAP in the resting condition.

Nitroglycerin sensitises in healthy subjects CNS structures involved in migraine pathophysiology: evidence from a study of nociceptive blink reflexes and visual evoked potentials.

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1 h and 4 h after administration of NTG (1.2 mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. We found a significant decrease in nBR pain and reflex thresholds both 1 and 4 h post-NTG. At the 4 h time point R2 latency was shorter (p=0.04) and R2 response area increased (p<0.01) after NTG but not after placebo. Habituation tended to become more pronounced after both NTG and placebo administration. There was a significant amplitude increase in the 5th VEP block (p=0.03) at 1h after NTG and in the 1st block (p=0.04) at 4 h. VEP habituation was replaced by potentiation at both delays after NTG; the change in habituation slope was significant at 1h (p=0.02). There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs.