Lessons From 8 Years' Experience of Hypothalamic Stimulation in Cluster Headache

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.

[1]  A. Straube,et al.  Quantitative Sensory Testing in Cluster Headache: Increased Sensory Thresholds , 2006, Cephalalgia : an international journal of headache.

[2]  Eric E. Abrahamson,et al.  The posterior hypothalamic area: chemoarchitecture and afferent connections , 2001, Brain Research.

[3]  J. Olesen The International Classification of Headache Disorders , 2008, Headache.

[4]  G. Broggi,et al.  Acute hypothalamic stimulation and ongoing cluster headache attacks , 2006, Neurology.

[5]  G. Broggi,et al.  Hypothalamic stimulation for intractable cluster headache: Long-term experience , 2006, Neurology.

[6]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[7]  M. Leone,et al.  A Review of Hormonal Findings in Cluster Headache. Evidence for Hypothalamic Involvement , 1993, Cephalalgia : an international journal of headache.

[8]  J. Schoenen,et al.  Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. , 2005, Brain : a journal of neurology.

[9]  G. Schaltenbrand,et al.  Einführung in die stereotaktischen Operationen : mit einem Atlas des menschlichen Gehirns = Introduction to stereotaxis, with an atlas of the human brain , 1959 .

[10]  Karl J. Friston,et al.  Correlation between structural and functional changes in brain in an idiopathic headache syndrome , 1999, Nature Medicine.

[11]  J. Ellrich,et al.  Impaired thermal perception in cluster headache , 2006, Journal of Neurology.

[12]  G. Broggi,et al.  Stimulation of occipital nerve for drug-resistant chronic cluster headache , 2007, The Lancet Neurology.

[13]  Till Sprenger,et al.  Hypothalamic Deep Brain Stimulation in Positron Emission Tomography , 2006, The Journal of Neuroscience.

[14]  A. Loewy Forebrain nuclei involved in autonomic control. , 1991, Progress in brain research.

[15]  A. May Cluster headache: pathogenesis, diagnosis, and management , 2005, The Lancet.

[16]  Richard S. J. Frackowiak,et al.  Posterior hypothalamic activation in paroxysmal hemicrania , 2006, Annals of neurology.

[17]  P. Goadsby,et al.  Hypothalamic activation after stimulation of the superior sagittal sinus in the cat: a Fos study , 2004, Neurobiology of Disease.

[18]  C. Büchel,et al.  Functional magnetic resonance imaging in spontaneous attacks of SUNCT: Short‐lasting neuralgiform headache with conjunctival injection and tearing , 1999, Annals of neurology.

[19]  P. Ferroli,et al.  Hypothalamic Deep Brain Stimulation for the Treatment of Chronic Cluster Headaches: A Series Report , 2004, Neuromodulation : journal of the International Neuromodulation Society.

[20]  T. Sand,et al.  Thermal Sensitivity in Unilateral Headaches , 1998, Cephalalgia : an international journal of headache.

[21]  Pietro Cortelli,et al.  Effect on Sleep of Posterior Hypothalamus Stimulation in Cluster Headache , 2007, Headache.

[22]  G. Manzoni Male Preponderance of Cluster Headache is Progressively Decreasing Over the Years , 1997, Headache.

[23]  L. Watkins,et al.  Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients , 2007, The Lancet.

[24]  J. Schoenen,et al.  Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study , 2007, The Lancet Neurology.

[25]  G. Broggi,et al.  Long-term follow-up of bilateral hypothalamic stimulation for intractable cluster headache. , 2004, Brain : a journal of neurology.

[26]  B. Barbiroli,et al.  Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy , 2006, Neurology.

[27]  J. Lirng,et al.  Reduction in hypothalamic 1H-MRS metabolite ratios in patients with cluster headache , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[28]  N. Barbaro,et al.  Chronic stimulation of the posterior hypothalamic region for cluster headache: technique and 1-year results in four patients. , 2007, Journal of neurosurgery.

[29]  I. Garza Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series , 2009 .

[30]  S. Naccarato,et al.  Prevalence and incidence of cluster headache in the Republic of San Marino. , 2003 .

[31]  A. May,et al.  Specific hypothalamic activation during a spontaneous cluster headache attack , 2004, Neurology.

[32]  G. Nappi,et al.  Double Blind Comparison of Lithium and Verapamil in Cluster Headache Prophylaxis , 1990, Headache.

[33]  C. Sherrington Integrative Action of the Nervous System , 1907 .

[34]  E. Fliers,et al.  The Human Hypothalamus: Basic and Clinical Aspects , 2004 .

[35]  T. Bartsch,et al.  Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area , 2004, Pain.

[36]  P. Cortelli,et al.  Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients , 2007, European journal of neurology.

[37]  Timothy Edward John Behrens,et al.  Connectivity of an effective hypothalamic surgical target for cluster headache , 2007, Journal of Clinical Neuroscience.

[38]  R. Leak,et al.  The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems , 2001, Neuroreport.

[39]  A Franzini,et al.  Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. , 2001, The New England journal of medicine.

[40]  M. Leone,et al.  Coexistence of TACS and Trigeminal Neuralgia: Pathophysiological Conjectures , 2006, Headache.

[41]  Krishna Kumar,et al.  Headache Secondary to Deep Brain Implantation , 1998, Headache.

[42]  Dudley H. Davis,et al.  Textbook of Stereotactic and Functional Neurosurgery , 1998 .

[43]  R. Burstein,et al.  Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. , 2000, Journal of neurophysiology.

[44]  A. Loewy Chapter 12 Forebrain nuclei involved in autonomic control , 1991 .

[45]  R. Lipton,et al.  A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. , 1997, Brain : a journal of neurology.

[46]  K. Jellinger,et al.  Central autonomic network: functional organization and clinical correlations , 1998 .

[47]  Massimo Leone,et al.  Deep brain stimulation in headache , 2006, The Lancet Neurology.

[48]  Christian Büchel,et al.  Hypothalamic activation in cluster headache attacks , 1998, The Lancet.

[49]  J. Roberts,et al.  Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord , 2001, Neuroscience.

[50]  G. Broggi,et al.  Spontaneous neuronal activity of the posterior hypothalamus in trigeminal autonomic cephalalgias , 2007, Neurological Sciences.

[51]  P. Ferroli,et al.  Stimulation of the Posterior Hypothalamus for Treatment of Chronic Intractable Cluster Headaches: First Reported Series , 2003 .

[52]  J. Brobeck The Integrative Action of the Nervous System , 1948, The Yale Journal of Biology and Medicine.