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Functional Neurosurgery and Anesthetic Considerations Susan M Ryan, Ph. D, MD Associate Clinical Professor Functional Neurosurgery and Anesthetic Considerations Susan M Ryan, Ph. D, MD Associate Clinical Professor Department of Anesthesia, UCSF 2006

What is Functional Neurosurgery? “Neurosurgery intended to improve or restore function by altering underlying What is Functional Neurosurgery? “Neurosurgery intended to improve or restore function by altering underlying physiology”

Areas of Functional Neurosurgery • • • Movement disorders Seizures Pain syndromes Psychiatric disorders Areas of Functional Neurosurgery • • • Movement disorders Seizures Pain syndromes Psychiatric disorders Peripheral nerve injuries

Areas of Expansion • Movement disorders • Seizures • Psychiatric disorders Areas of Expansion • Movement disorders • Seizures • Psychiatric disorders

Neurosurgical Techniques • Deep brain stimulation (DBS) • Selective ablation electrodes • Implantation viral Neurosurgical Techniques • Deep brain stimulation (DBS) • Selective ablation electrodes • Implantation viral vectors stem cells • Cranial nerve/ peripheral electrical stimulation

Functional Neurosurgery • Began in mid-1900’s • Eclipsed by effective medications • Now: Non-responders Functional Neurosurgery • Began in mid-1900’s • Eclipsed by effective medications • Now: Non-responders Advanced cases

Neurosurgical Techniques • Deep brain stimulation Best established use: Parkinson’s Disease • Vagal nerve Neurosurgical Techniques • Deep brain stimulation Best established use: Parkinson’s Disease • Vagal nerve stimulation Best established use: Seizure disorders

DBS/VNS Studies in Progress • • • Obesity Fibromyalgia Cluster headache Tourette’s Syndrome Depression DBS/VNS Studies in Progress • • • Obesity Fibromyalgia Cluster headache Tourette’s Syndrome Depression Obsessive Compulsive Disorder

DBS for Parkinson’s Disease DBS for Parkinson’s Disease

Clinical Features • ‘Pill-rolling’ tremor • Masked faces • ‘Cog-wheel’ rigidity • Festinating gate Clinical Features • ‘Pill-rolling’ tremor • Masked faces • ‘Cog-wheel’ rigidity • Festinating gate • Bradykinesia

Pathologic Features • Progressive neuronal death • Dopamine neurons of substantia nigra • Non- Pathologic Features • Progressive neuronal death • Dopamine neurons of substantia nigra • Non- dopamine populations in CNS and PNS • Bulbar function • Sympathetic chain • Parasympathetics of the gut

Basal Ganglia in PD Basal Ganglia in PD

Treatment • Medications • L-dopa + periph. inhibitor (Sinamet) • Dopamine agonists • MAO Treatment • Medications • L-dopa + periph. inhibitor (Sinamet) • Dopamine agonists • MAO inhibitors • COMT inhibitors • Amantadine

DBS Surgery • Goal: Improvement in PD symptoms • Tremor • Rigidity • Hypokinesia DBS Surgery • Goal: Improvement in PD symptoms • Tremor • Rigidity • Hypokinesia • Gait • Balance

DBS Surgery • Placement of stereotactic frame prior to procedure • MRI to confirm DBS Surgery • Placement of stereotactic frame prior to procedure • MRI to confirm coordinates

DBS Surgery • Stereotactic head frame attached to bed • Pt placed in sitting DBS Surgery • Stereotactic head frame attached to bed • Pt placed in sitting position

DBS Stereotactic Surgery • Drill hole in skull to allow electrode placement for recording DBS Stereotactic Surgery • Drill hole in skull to allow electrode placement for recording & stimulation

DBS Stereotactic Surgery • Electrode passed slowly to record single cells in nucleus of DBS Stereotactic Surgery • Electrode passed slowly to record single cells in nucleus of interest

DBS Stereotactic Surgery • Visual and auditory feedback of cell location and characteristics DBS Stereotactic Surgery • Visual and auditory feedback of cell location and characteristics

DBS Stereotactic Surgery • Listening for cell response during leg movement DBS Stereotactic Surgery • Listening for cell response during leg movement

DBS Surgery • • Find best location within the nucleus Place stimulating electrode Close DBS Surgery • • Find best location within the nucleus Place stimulating electrode Close burr hole, remove frame Induce general anesthesia • Tunnel leads • Place generator in upper chest wall • Wait to activate stimulator in outpatient setting

Anesthesia: DBS Generator placement • General anesthesia for generator placement • No particular anesthetic Anesthesia: DBS Generator placement • General anesthesia for generator placement • No particular anesthetic Propofol or inhaled agent work well Avoid dopamine antagonists Avoid demerol Muscle relaxants OK • Prevent or treat emergence hypertension • Not much pain in post-op setting

PD: Specific Issues • Risk of exacerbation Consider intraoperative continuation of medications • Hemodynamics PD: Specific Issues • Risk of exacerbation Consider intraoperative continuation of medications • Hemodynamics may be labile Degeneration of sympathetic ganglia Dopamine-related hypotension, hypovolemia

PD: Specific Issues • Airway or pulmonary compromise • Upper airway obstruction • Dysarthria PD: Specific Issues • Airway or pulmonary compromise • Upper airway obstruction • Dysarthria and history of choking • Restrictive ventilatory pattern • Aspiration risk

Patients with Existing DBS • DBS is usually on 24/7 for PD pts • Patients with Existing DBS • DBS is usually on 24/7 for PD pts • May be off at night in other conditions • Consider turning off prior to surgery

DBS: Surgical Risks • Intracerebral hemorrhage • Venous air embolism • Emotional lability DBS: Surgical Risks • Intracerebral hemorrhage • Venous air embolism • Emotional lability

DBS: Surgical Risks Intracerebral hemorrhage • Monitor patient for neurologic changes • Risk: 1. DBS: Surgical Risks Intracerebral hemorrhage • Monitor patient for neurologic changes • Risk: 1. 6% per lead • Avoid hypertension Keep SBP < 140 Consider arterial line Antihypertensives: labetalol, hydralazine

DBS: Surgical Risks Venous air embolism • Early detection • Communicate with surgeon • DBS: Surgical Risks Venous air embolism • Early detection • Communicate with surgeon • Support blood pressure • Provide O 2 • Airway plan

DBS: Surgical Risks Emotional Lability • Usually no treatment needed • Consider sedation PRN DBS: Surgical Risks Emotional Lability • Usually no treatment needed • Consider sedation PRN

DBS Outcomes Bilateral DBS of STN: • N = 49 • Assessed at 1, DBS Outcomes Bilateral DBS of STN: • N = 49 • Assessed at 1, 3, and 5 years • Assessed on and off meds and stimulation (Krack, et al, NEJM 349, 2003)

DBS Outcomes • Stimulation alone: significant improvement • Synergy between meds and stimulation • DBS Outcomes • Stimulation alone: significant improvement • Synergy between meds and stimulation • Allows decrease in medication doses • Improvement in L-dopa dyskinesias • Akinesia, speech, and freezing of gait all worsened (Krack, et al, NEJM 349, 2003)

DBS vs Medical Therapy • Randomized-pair trial: • DBS + optimized medical tx • DBS vs Medical Therapy • Randomized-pair trial: • DBS + optimized medical tx • Optimized medical tx • 75% of pairs favored DBS + meds Quality of life Severity of motor sxs off medication (Deuschl et al, NEJM, 355, 2006)

DBS: other motor diseases • Essential tremor • Dystonia • More sedation during MRI DBS: other motor diseases • Essential tremor • Dystonia • More sedation during MRI

DBS and Tourette’s • Motor/speech tics • Up to 1% school age children • DBS and Tourette’s • Motor/speech tics • Up to 1% school age children • 1/3 persist into adulthood

DBS for Tourette’s (Visser-Vandewalle, J. Neurosurg 99: 2003) DBS for Tourette’s (Visser-Vandewalle, J. Neurosurg 99: 2003)

DBS and Psychiatric Disease • Depression • Pilot in 2005 • 4/6 patients improved DBS and Psychiatric Disease • Depression • Pilot in 2005 • 4/6 patients improved >50% on testing • Currently at least 3 ongoing NIH trials • 10 to 20 patients per study

Vagus Nerve Stimulation Vagus Nerve Stimulation

Vagus: Mixed Sensory and Motor • 20% efferent: parasympathetic control of the heart and Vagus: Mixed Sensory and Motor • 20% efferent: parasympathetic control of the heart and gut viscera • 80% afferent: extensive connections to limbic and higher cortical systems • Animal studies VNS: EEG changes and seizure cessation

Vagal Nerve Stimulation • Approved device made by Cyberonics • Chronic, intermittent stimulation to Vagal Nerve Stimulation • Approved device made by Cyberonics • Chronic, intermittent stimulation to cervical vagus • Prevents and aborts seizures

Vagal Nerve Stimulation • Typical settings: • Automatic: 30 sec stimulation q 5 min Vagal Nerve Stimulation • Typical settings: • Automatic: 30 sec stimulation q 5 min • Additional manual: if pt feels aura, may wave wand over generator to activate stimulator

Vagal Nerve Stimulation • Results from 3 studies: • Significant decrease in seizures: 24%-35% Vagal Nerve Stimulation • Results from 3 studies: • Significant decrease in seizures: 24%-35% • Controls: low-level stimulation • Seizure frequency decreased further over time • Decreased medication doses

VNS Surgery • Performed under general anesthesia • Leads wrapped around L vagus in VNS Surgery • Performed under general anesthesia • Leads wrapped around L vagus in neck • Only L, and only unilateral • Generator placed upper left chest

Final Electrode/tether Placement Anchor Tether Positive Electrode Negative Electrode Final Electrode/tether Placement Anchor Tether Positive Electrode Negative Electrode

VNS Surgery • Possible intraop complications with lead testing: • Arrhythmias- transient sinus arrest VNS Surgery • Possible intraop complications with lead testing: • Arrhythmias- transient sinus arrest • Labile hemodynamics • Airway obstruction (vocal cord stimulation)- if not intubated

VNS Surgery • Surgical complications: • Infection: 2. 9% • Hoarseness or temporary vocal VNS Surgery • Surgical complications: • Infection: 2. 9% • Hoarseness or temporary vocal cord paralysis: 0. 7% • Hypesthesia or lower left facial paralysis: 0. 7%

VNS Surgery: Chronic Side Effects • Hoarseness • Cough • Paresthesias • Dyspepsia • VNS Surgery: Chronic Side Effects • Hoarseness • Cough • Paresthesias • Dyspepsia • Disrupted sleep • Worsening sleep apnea

VNS: Anesthesia • Pre-op considerations: • Take usual seizure medications • CBC, electrolytes • VNS: Anesthesia • Pre-op considerations: • Take usual seizure medications • CBC, electrolytes • EKG • cardiac medications?

VNS: Anesthesia • May use local, MAC, or GA • Usually GA- no restriction VNS: Anesthesia • May use local, MAC, or GA • Usually GA- no restriction on agents • Endotracheal tube • Blood loss is minimal

VNS: Anesthesia • Anti-seizure medications induce hepatic enzymes-- higher anesthetic doses? • Post-op seizures VNS: Anesthesia • Anti-seizure medications induce hepatic enzymes-- higher anesthetic doses? • Post-op seizures are common- be prepared • Incidence of transient vocal cord paralysis

Chronic VNS • Turn off for other surgery • Restart in recovery Chronic VNS • Turn off for other surgery • Restart in recovery

VNS for Depression • Seizure pts with VNS: happier over time! • N = VNS for Depression • Seizure pts with VNS: happier over time! • N = 60 pts • previously failed numerous treatments • 2 weeks on meds only • 2 weeks stim adjust + meds • 8 weeks fixed stimu + meds

VNS for Depression • Open label study: • 30. 5% of patients responded with VNS for Depression • Open label study: • 30. 5% of patients responded with significant decrease in depression rating scale • 15% full remission • Substantial functional improvement, even in non-responders

VNS for Depression • Placebo controlled study: • • N= 225 VNS-responding patients: 15% VNS for Depression • Placebo controlled study: • • N= 225 VNS-responding patients: 15% Placebo-responding patients: 10% Lower levels of stimulation • Much to figure out, although now FDA approved

Other ongoing VNS studies • Cervical VNS: • • PTSD Panic disorder OCD Rapid-cycling Other ongoing VNS studies • Cervical VNS: • • PTSD Panic disorder OCD Rapid-cycling bipolar disorder • Bilateral diaphragmatic VNS • Morbid obesity

Functional Neurosurgery • DBS • Targets stimulation based on neuroanatomy. Tailors stim to the Functional Neurosurgery • DBS • Targets stimulation based on neuroanatomy. Tailors stim to the disorder. • Invasive. • Requires neurosurgery • VNS • Simultaneous stimulation of multiple tracts & nuclei. • No specific target. Same stimulation for a number of disorders. • Much less invasive. Does not require neurosurgeon. • Procedure in search of an application?