Chronic cluster headache neuromodulation MILAN ITALY ANGELO FRANZINI MASSIMO LEONE CARLO MARRAS GIOVANNI TRINGALI GIANNI BROGGI SELECTION CRITERIA ORBITAL REGION PAIN BOUTS (VIOLENT UNBEARABLE) OCULAR VEGETATIVE SYMPTOMS DAILY PAIN ATTACKS LASTING ALMOST 1 YEAR DRUGS INEFFECTIVE INCLUDING TRIPTANS AND STEROIDS Refractoy to sphenopaltine ganglion procedures saggital The original coronal observation axial PET-activity (functional change) voxel based morphometry (structual change) Figure: PET-activity in 9 patients during the acute cluster headache attack (upper row) and structual grey matter changes using voxel based morphometry in 19 patients (lower row). Sano K. 1970 Franzini et al. 2003 May A. 1999 The Sano graphic reconstruction of electrodes tracks and the fusion between RM and postoperative CT with electrodes implanted within the posterior hypothalamus The first clinical result STIMULATION 180 Hz PARAMETERS 90 usec 1-2.5 Volts STEREOTACTIC COORDINATES AND TECHNICAL PROBLEMS The AP(y) value of the target coordinates is affected by “errors” due to the midbrain orientation and shape variability( 1-4 mm) Correction of the AP(y) error INTRAOPERATIVE EVOKED RESPONSE • -Vertigo, ocular movement disturbances(>3V.) • -Sense of fear(>4V.) – Bipolar stimulation at the target The frequency of single unit action potentials is about 15-16 Hz 100 ms Neuronavigator + dedicated stereotactic atlas Hypothalamic DBS benefits intractable CCH (18 implants) N. of attacks/month 1-5 years follow-up 200 responders patients 180 Implant 160 140 120 100 mean ± SE 80 60 40 20 0 2 4 6 8 -1 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 months DBS ipotalamica per la Cefalea a Grappolo e TACs– Data base, Istituto Neurologico C.Besta 2005 Before surgery HYPOTHALAMIC NEUROMODULATION IN 2 years after surgery CCH AND SUNCT SEEMS TO BE THE MOST 4 years after surgery PROMISING APPLICATION OF DBS IN A REFRACTORY PAINFUL CONDITION 100 90 80 70 60 50 40 30 20 10 0 pain bouts HYPOTALAMIC DBS “BENEFITS” CCH AND SUNCT Chronic Cluster headaches became episodic and the number of pain bouts is so considerably reduced allowing a quite normal life REALLY ONLY 6 OUT 18 PATIENTS (27%) ARE “CURED” COMPLETELY FREE FROM PAIN BOUTS 4/22 patients resulted absolutely non responders 20% A young female patient with bilateral Hypothalamic implant Had a normal pregnancy and a sound newborn 2003 : a new therapy for an otherwise refractory disease has been introduced 2005 :The Italian experience is confirmed FIVE PATIENTS = TWO NON RESPONDERS (40%) Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series T Bartsch , MO Pinsker , D Rasche , T Kinfe , F Hertel , HC Diener , V Tronnier , HM Mehdorn ,J Volkmann , G Deuschl & JK Krauss University Hospital Schleswig-Holstein, Kiel, University Hospital Schleswig-Holstein, Lübeck, SHG-Klinik, Idar-Oberstein, University of Essen, Essen, Medical School Hannover, Hannover, Germany SIX PATIENTS : THREE NON RESPONDERS ( 50%) SUNCT Short-lasting, Unilateral, Neuralgiform headache attacks with Conjunctival injection and Tearing Pain attacks are similar to cluster headache but are shorter and Much more frequent ( even 100 attacks per day ) Deep brain stimulation to relieve drug-resistant SUNCT Massimo Leone, MD 1 *, Angelo Franzini, MD 2, Giovanni D'Andrea, MD 3, Giovanni Broggi, MD 2, Gerardo Casucci, MD 4, Gennaro Bussone, MD 1 Received: 4 February 2005; Accepted: 27 March 2005 Leone M et al. Ann Neurol 2005, in press May A et al. Lancet 1998 Responsiveness of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing to hypothalamic deep brain stimulation. Lyons MK, Dodick DW, Evidente VG. 1 Departments of Neurological Surgery and, 2 Neurology, Mayo Clinic Arizona, Pheonix, Arizona. J Neurosurg. 2008 Sep 26. SUNCT SUNCT (f-MRI) SUNCT - DBS May et al. Ann Neurol 1999 Leone M et al. Ann Neurol 2005 Sprenger etal. Cephalalgia 2004 THE STIMULATION OF THE POSTERIOR HYPOTHALAMUS RESULTED UNEVENTFUL IN CHRONIC NEUROPATHIC PAIN OF THE FACE 3 patients POSTERIOR HYPOTHALAMIC STIMULATION IN MS PATIENTS AFFECTED FROM TRIGEMINAL NEURALGIA RELIEVED ONLY PAIN PAROXYSMS IN THE FIRST BRANCH OF THE TRIGEMINAL NERVE 5 PATIENTS In 3 of these patients RF retrogasserian Thermorhizotomies were performed to obtain pain relief in the II and III branches I branch DBS II III branches TRZ CGRP VIP Modified from Silberstein, Lipton & Goadsby 2002 Effect on Sleep of Posterior Hypothalamus Stimulation in Cluster Headache Roberto Vetrugno, MD, PhD; Giulia Pierangeli, MD; Massimo Leone, MD; Gennaro Bussone, MD; Angelo Franzini, MD; Giovanni Brogli, MD; Roberto D'Angelo, MD; Pietro Cortelli, MD; Pasquale Montagna, MD CHRONIC CLUSTER HEADACHE Central versus peripheral neuromodulation Posterior hypothalamus promotes activation/inhibition of Trigeminal Nucleus Caudalis neurons Bartsch et al. Pain 2004; 109: 367–8 Ipotalamo e dolore - Leone M. 2005 CGRP C1 C2 inputs VIP Modified from Silberstein, Lipton & Goadsby 2002 CENTRAL VERSUS PERIPHERAL NEUROMODULATION IN CHRONIC CLUSTER HEADACHE 100,00% 90,00% 80,00% 70,00% 60,00% 50,00% 40,00% 30,00% 20,00% 10,00% 0,00% Hypothalamus GON expectancy of therapeutic effect within the third month of neurostimulation 2 FREE EXTENSION LEAD FOR DBS 1 DUAL CHANNELS IPG (KINETRA) “ GATES ” FOR NEUROMODULATION OF THE TRIGEMINAL-AUTONOMIC SYSTEM AND RELATED PAINFUL SYNDROMES SPG Long term results All the patients ( 7/22) who had the IPG exhausted requested the immediate replacement RESULTS • 70 % reduction of days with pain bouts • No clinically relevant side effects (sympathotonic orthostatic hypotension revealed by instrumental 24hrs monitoring)) • Withdrawal of steroids and triptans • Return to normal life of responders (70%) • Low doses drugs prophylaxys (29%) verapamil, methysergide, valproate, topiramate, gabapentin,pizotifen,indomethacin. Non Responders = 30% RESPONDERS CONCLUSIONS 70% 18 pts limits • Long time-lapse between surgery 60% 5 pts and pain bouts reduction ( 10- 60 days ), suggesting a neurotransmitters modulation or a 50% 6 pts neuronal network reset Non responders ? 11pts (30-50%) 75% 4 pts Peripheral neuromodulation ? ? 1 patient Thanks for attention.