Commentary on Leone M et al., Lessons from 8 Years' Experience of Hypothalamic Stimulation in Cluster Headache

Abstract

Commentary on Leone M et al., Lessons from 8 years' experience of hypothalamic stimulation in cluster headache n this issue, Leone et al. review the world experience with deep-brain stimulation (DBS) of the ipsilateral posterior hypothalamic region for medically intractable cluster headache (CH). The article is from the centre that pioneered this procedure and that has the greatest experience to date (16 patients). Results and physiological findings from 50 patients are described. Data from some of these patients were transmitted to the authors as personal communications. The procedure is fascinating in many respects. It is one of a number of new DBS applications that have been proposed based on findings from functional brain imaging. The target was selected as the region that has altered metabolic activity during a CH attack, as measured using H2 15 O-positron emission tomography. The time course for wash-in and wash-out of benefit has been formally studied in only one patient published thus far (1), but based on this and anecdotal observations, the time course for wash-in and wash-out of several weeks suggests long-term changes in synaptic efficacy may be taking place. The mechanism underlying its effectiveness, in those patients where it is effective, is not totally clear. The authors point out that in experimental animals, facial sensation may be conveyed to the hypothalamus by neurons of the trigeminohypothalamic tract, and that nociceptive inputs to the trigeminal nucleus caudalis can be modulated by differential regulation of orexin A and B receptors in the posterior hypothalamus. The authors mention several times that the procedure is now 'established' in the treatment of CH, but not all would agree with this. As shown in table 1, different centres performing this procedure have consistently shown that up to 50% of patients are non-responders. Formal blinded controlled studies have not been done. Our own experience now includes eight CH patients with at least 1 year's follow-up. Five of our eight patients are considered 'responders' based on a 50% reduction in either headache frequency or intensity, comparing headache diaries at last time point, compared with the preoperative baseline. Of the three non-responders, two in fact no longer use the device. For this invasive therapy to become accepted, a better predictor of outcome must be found, to avoid operating on patients who will receive no or minimal benefit. Predictors of outcome could potentially be found in detailed analysis of headache characteristics, responses to medication, or functional imaging features.

Deep brain stimulation for cluster headache

“…21 Of eight patients implanted in California, five demonstrated a greater than 50% reduction in headache intensity or frequency by at least one year of follow-up; however, none have been reported as pain free. 22,23 Most recently a multi-centre series of six patients implanted in Germany reports three patients almost pain free and three treatment failures. 24 Additional presented abstracts not published in detail and unpublished cases are reported elsewhere.…”

“…29 This may be explained by the location of the electrode tip posterior to the mammillo-thalamic tract, believed by some to represent anterior periaqueductal grey rather than posterior hypothalamus. 22 In general, outcomes are variable but clearly the procedure can be startlingly effective. Three out of five studies have operated on 6 to 8 patients and reported a 50% or greater success rate, defined as either pain free or having a greater than 50% improvement in frequency or intensity of headaches.…”

‘Dual’ occipital and supraorbital nerve stimulation for primary headache

“…The study of dual stimulation for CCH should also be considered, because high responder rates (compared with ONS) may prevent some patients having to consider deep brain stimulation (DBS) (16,17), which would be a definite advantage as DBS carries a risk of serious adverse events (18). However, DBS may still be offered to some patients who fail to respond to PNS, or if DBS continues to offer a greater chance to become pain free/almost pain free.…”

Deep Brain Stimulation for the Treatment of Aggressive Behaviour: Considerations on Pathophysiology and Target Choice

“…The reported efficacy of both the VC/VS and the pHyp targets led us to consider the possible structure connecting the 2 above-mentioned DBS target regions. The only well-described anatomical bundle of fibres connecting these 2 areas is the mesolimbic pathway, a dopaminergic pathway primarily connecting the VTA (located in the so-called “posterior hypothalamic region” defined by Starr [14]) with the nucleus accumbens, part of the VS complex.…”

“…Some disputations about the fact that the pHyp target of Sano et al [13] be at the level of the diencephalon-mesencephalic junction (the “posterior hypothalamic region”) [14] or definitely in the ventral tegmental area (VTA) have to be considered [15,16] in order to better understand the anatomical substrate of the disorder.…”