Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

Recently, functional imaging data have underscored the crucial role the hypothalamus plays in cluster headache, one of the most severe forms of primary headache. This prompted the application of hypothalamic deep brain stimulation. Yet, it is not apparent how stimulation of an area that is thought to act as a pace-maker for acute headache attacks is able to prevent these attacks from occurring. We addressed this issue by examining 10 operated chronic cluster headache patients, using H215O-positron emission tomography and alternately switching the hypothalamic stimulator on and off. The stimulation induced activation in the ipsilateral hypothalamic gray (the site of the stimulator tip), the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We additionally observed deactivation in the middle temporal gyrus, posterior cingulate cortex, and contralateral anterior insula. Both activation and deactivation are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission and notably in acute cluster headache attacks. Our data argue against an unspecific antinociceptive effect or pure inhibition of hypothalamic activity. Instead, the data suggest a hitherto unrecognized functional modulation of the pain processing network as the mode of action of hypothalamic deep brain stimulation in cluster headache.

[1]  K. Sano,et al.  Posteromedial Hypothalamotomy in the treatment of tractable pain,. , 1975, Confinia neurologica.

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

[3]  V. Cox,et al.  Analgesia for formalin-induced pain by lateral hypothalamic stimulation , 1991, Brain Research.

[4]  Tipu Z. Aziz,et al.  Deep brain stimulation for pain relief: A meta-analysis , 2005, Journal of Clinical Neuroscience.

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

[6]  N. Raskin,et al.  Headache May Arise From Perturbation of Brain , 1987, Headache.

[7]  P. Goadsby.  Pathophysiology of cluster headache: a trigeminal autonomic cephalgia , 2002, The Lancet Neurology.

[8]  A. May.  Headache: lessons learned from functional imaging. , 2003, British medical bulletin.

[9]  B. Lumb,et al.  Inhibitory effects evoked from the anterior hypothalamus are selective for the nociceptive responses of dorsal horn neurons with high- and low-threshold inputs. , 1997, Journal of neurophysiology.

[10]  Karl J. Friston,et al.  A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. , 2004, Brain : a journal of neurology.

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

[12]  R. Vertes,et al.  Descending projections of the posterior nucleus of the hypothalamus: Phaseolus vulgaris leucoagglutinin analysis in the rat , 1996, The Journal of comparative neurology.

[13]  Karl J. Friston,et al.  Functional neuroanatomy of the human brain: positron emission tomography--a new neuroanatomical technique. , 1994, Journal of anatomy.

[14]  R. Moore,et al.  Circadian rhythms: basic neurobiology and clinical applications. , 1997, Annual review of medicine.

[15]  Krishna Kumar,et al.  Deep brain stimulation for intractable pain: a 15-year experience. , 1997, Neurosurgery.

[16]  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.

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

[18]  N. Dafny,et al.  Lateral hypothalamus: Site involved in pain modulation , 1996, Neuroscience.

[19]  Sebastiaan Overeem,et al.  The hypothalamus in episodic brain disorders , 2002, The Lancet Neurology.

[20]  R R Tasker,et al.  Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study. , 2000, Journal of neurosurgery.

[21]  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.

[22]  A. Randich,et al.  Vagal afferent modulation of nociception , 1992, Brain Research Reviews.

[23]  G. Mazars,et al.  [Results of the stimulation of the spinothalamic fasciculus and their bearing on the physiopathology of pain]. , 1960, Revue neurologique.

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

[25]  G. Broggi,et al.  Deep Brain Stimulation for Intractable Chronic Cluster Headache: Proposals for Patient Selection , 2004, Cephalalgia : an international journal of headache.

[26]  J. Stein,et al.  Thalamic field potentials during deep brain stimulation of periventricular gray in chronic pain , 2002, Pain.

[27]  P. Ferroli,et al.  STIMULATION OF THE POSTERIOR HYPOTHALAMUS FOR TREATMENT OF CHRONIC INTRACTABLE CLUSTER HEADACHES : FIRST REPORTED SERIES , 2003 .

[28]  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.

[29]  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.

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