ATI NEUROSTIMULATOR SYSTEM for cluster headaches Autonomic Technologies Inc.

Cluster Headaches- overview “Suicide” Headaches Painful and debilitating- interferes with normal daily functioning Symptoms: excruciating pain typically located above one eye, swelling, redness or tearing of the eye, drooping eyelid , facial redness and sweating Cyclical pattern of attacks with or without remission Autonomic Technologies Inc.

Cluster Headaches- overview Autonomic Technologies Inc.

Cluster Headaches- pathophysiology Trigeminal Nerve Pathway Sphenopalatine Ganglion Autonomic Technologies Inc.

Cluster Headaches- pathophysiology TRIGEMINAL NERVE PATHWAY Trigeminal Nerve- responsible for sensation of the face (sensory fibers produce feelings of touch, temperature and pain) Three Branches *Maxillary Branch Ophthalmic Branch Mandibular Branch Autonomic Technologies Inc.

Cluster Headaches- pathophysiology TRIGEMINAL NERVE PATHWAY Responsible for 1. Autonomic (Involuntary) Symptoms: (eye drooping and tearing, stuffed or running nose, swelling, sweating, ect) 2. Pain - Neurotransmitters - Vasodilators Autonomic Technologies Inc.

Cluster Headache- pathophysiology SPHENOPALATINE GANGLION (SPG) Large, extra-cranial parasympathetic ganglion Located deep in the face, behind the nose (on each side) Autonomic Technologies Inc.

Cluster Headache- pathophysiology SPHENOPALATINE GANGLION (SPG) The SPG mediates functioning of the trigeminal nerve fibers that innervate the face Role in severe headache pain has been studied for over 100 years- many therapies target the SPG Autonomic Technologies Inc.

Treatment Options Drugs - Intranasal anesthetics (Lidocaine) - Injectable medications (Sumatriptan) Disadvantages: systemic side effects, dangerous for patients with cardiovascular risk factors, patients can become immune, don’t decrease attack frequency Inhaled Oxygen Disadvantages: impractical and inconvenient, doesn’t decrease attack frequency Deep Brain Stimulation Disadvantages: surgical risk, internal bleeding, infection Autonomic Technologies Inc.

ATI NEUROSTIMULATOR SYSTEM Autonomic Technologies Inc.

Implanted Neurostimulator System Contains a neurostimulator body, a lead and a fixation plate Neurostimulator Body - Small size, 1.5 grams in weight and 5 mm in thickness - Implanted in the gum above the second molar using oral surgery - Programmed by a physician - Rechargeable Lead - Extends from the neurostimulator body to the SPG - 6 electrodes stimulate the SPG nerve bundle (ganglion) Fixation Plate - Anchored to the zygomatic process of the maxilla (cheekbone) Autonomic Technologies Inc.

ATI NEUROSTIMULATOR SYSTEM Autonomic Technologies Inc.

Implant Procedure Prior to the surgery, patient gets a CT scan Surgery done by oral surgeon under general anesthesia (minimally invasive) Small incision made in the mouth in the upper gum Neurostimulator is implanted and incision is closed Autonomic Technologies Inc.

Patient Control of Neurostimulator Patients control their own neurostimulator as needed Use a remote control device Autonomic Technologies Inc.

How it works! High frequency stimulation (120 Hz) of the SPG paralyzes maxillary nerve sensory fibers, thus relieving sensation of pain in its peripheral targets Possible Mechanisms 1. Acute relief- physiological block of parasympathetic efferents to trigeminal nerve 2. Long term relief- depletion of stored NT in parasympathetic efferents to trigeminal nerve Autonomic Technologies Inc.

Neurostimulator Device Benefits Acute Pain Relief Reduction in Cluster Attack Frequency *68% of patients experienced clinically significant improvements in acute head disability, headache frequency, or both Quality of life improvements 75% of patients reported clinically significant improvements in both their physical and mental quality of life Autonomic Technologies Inc.

Neurostimulator Device Complications Surgical Side Effects Swelling or discomfort in mouth and gums Pain in face, cheek, gum, mandible, nose or incision site Tooth pain or sensitivity Hematoma Seroma Infection (incision site infection) Autonomic Technologies Inc.

Neurostimulator Device Complications Neurostimulation Side Effects Sensory Disturbances (81% of patients) Mild paresis of muscles around naslabial fold Dry eye, tearing or tenderness in mouth Serious Adverse Events Neurostimulator lead misplacement Neurostimulator lead migration Neurostimulator explantation Autonomic Technologies Inc.

Why Use this Device? Clinical Benefits - Relieves cluster attack pain - Reduces frequency of cluster attacks - Improves quality of life Advantages over other options - Practical and portable - Unlimited use daily - No systemic side effects - Can be used by patients with cardiovascular symptoms or vascular disease Autonomic Technologies Inc.

Why Use this Device? Autonomic Technologies Inc.

Current Availability Currently available in Germany and Denmark only Prescription Required Cost? Autonomic Technologies Inc.

Patient Protocols Following Oral Surgery Hospital Stay: 1-2 days Avoid rapid bending, twisting or weight lifting for 6-8 weeks Avoid touching or putting pressure on the implant site Autonomic Technologies Inc.

Patient Protocols Life with your ATI Neurostimulator Almost all normal activities can be resumed Can pass through metal detectors and full body X-ray machines Can get a full body MRI Use the device for as long as needed! Discuss cluster headache medication changes with your doctor Autonomic Technologies Inc.