Neurostimulation Jeffrey R. Scott, Ph.D.

Brain Anatomy

Video – Brain Anatomy

Conditions – Essential Tremor Essential Tremor A tremor of unknown cause (usually of the hands and head) that develops in older people; often mistaken for Parkinsonism but is not life- threatening and can usually be kept under control.

Conditions – Essential Tremor Who is afflicted with Essential Tremor (ET)? Essential tremor is the most common movement disorder, affecting an estimated five million people in the U.S. Some figures estimate that one in 20 people over age 40 and one in 5 people over age 65 have ET. While ET can occur at any age, it most often strikes for the first time during adolescence or in middle age (between ages 40 and 50). What Are the Symptoms of Essential Tremor? The primary symptoms associated with essential tremor include: - Uncontrollable shaking that occurs for brief periods of time - Shaking voice - Nodding head - Tremors that worsen during periods of emotional stress - Tremors that get worse with purposeful movement - Tremors that lessen with rest - Balance problems (in rare cases)

Conditions – Dystonia Dystonia Abnormal tonicity of muscle, characterized by prolonged, repetitive muscle contractions that may cause twisting or jerking movements of the body or a body part.

Conditions – Dystonia What are the symptoms? - Include involuntary muscle contractions that cause repetitive movements or distorted postures - Begin in a single area, such as your foot, hand or neck - May occur during a specific action, such as handwriting - May worsen with stress, fatigue or anxiety - May become more noticeable over time Eyelids. Rapid blinking or involuntary spasms causing your eyes to close (blepharospasm) can make you functionally blind. Neck. In cervical dystonia, contractions cause your head to twist and turn to one side, or pull forward or backward, sometimes causing pain. Face, head and neck. In craniofacial dystonia, your face, head or neck muscles are affected by contractions. Oromandibular dystonia affects your jaw movement or tongue and may cause slurred speech or difficulty swallowing. Vocal cords. Some forms of dystonia affect muscles that control your vocal cords (spasmodic dysphonia), causing a tight or whispering voice. Hand and forearm. Some types of dystonia only occur while you're conducting a repetitive activity. In musician's dystonia, your ability to play a specific instrument may be impaired. In writer's cramp, your hand and forearm muscles are affected while you're writing. Dystonia also may occur during other specific tasks.

Conditions – Parkinson’s Disease Parkinson’s Disease A progressive nervous disease occurring most often after the age of 50, associated with the destruction of brain cells that produce dopamine and characterized by muscular tremor, slowing of movement, partial facial paralysis, peculiarity of gait and posture, and weakness.

Conditions – Parkinson’s Disease What are the symptoms? - Tremor. Your tremor, or shaking, usually begins in your limb, often your hand or fingers. You may notice a back-and-forth rubbing of your thumb and forefinger, known as a pill-rolling tremor. One characteristic of Parkinson's disease is tremor of your hand when it is relaxed (at rest). - Slowed movement (bradykinesia). Over time, Parkinson's disease may reduce your ability to move and slow your movement. This may make simple tasks difficult and time-consuming. Your steps may become shorter when you walk, or you may find it difficult to get out of a chair. Also, your feet may stick to the floor as you try to walk, making it difficult to move. - Rigid muscles. Muscle stiffness may occur in any parts of your body. The stiff muscles can limit your range of motion and cause you pain. Impaired posture and balance. Your posture may have become stooped, or you may have balance problems as a result of Parkinson's disease. - Loss of automatic movements. In Parkinson's disease, you may have a decreased ability to perform unconscious movements, including blinking, smiling or swinging your arms when you walk. You may no longer gesture when talking. Speech changes. You often may have speech problems as a result of Parkinson's disease. You may speak softly, quickly, slur or hesitate before talking. Your speech may be more of a monotone, rather than with the usual inflections. Writing changes. Writing may appear small and become difficult.

Conditions – OCD Obsessive Compulsive Disorder An anxiety disorder characterized by recurrent and persistent thoughts and feelings and repetitive, ritualized behaviors.

Conditions – OCD What are the obsessive symptoms? OCD obsessions are repeated, persistent and unwanted ideas, thoughts, images or impulses that you have involuntarily and that seem to make no sense. These obsessions typically intrude when you're trying to think of or do other things. Obsessions often have themes to them, such as: - Fear of contamination or dirt - Having things orderly and symmetrical - Aggressive or horrific impulses - Sexual images or thoughts - Obsession symptoms and signs may include: - Fear of being contaminated by shaking hands or by touching objects others have touched - Doubts that you've locked the door or turned off the stove - Thoughts that you've hurt someone in a traffic accident - Intense stress when objects aren't orderly or facing the right way - Images of hurting your child - Impulses to shout obscenities in inappropriate situations - Avoidance of situations that can trigger obsessions, such as shaking hands - Replaying pornographic images in your mind - Dermatitis because of frequent hand washing - Skin lesions because of picking at your skin - Hair loss or bald spots because of hair pulling

Conditions – OCD What are the complusive symptoms? OCD compulsions are repetitive behaviors that you feel driven to perform. These repetitive behaviors are meant to prevent or reduce anxiety related to your obsessions. Compulsions typically have themes, such as: - Washing and cleaning - Counting - Checking - Demanding reassurances - Performing the same action repeatedly - Orderliness - Compulsion symptoms and signs may include: - Hand washing until your skin becomes raw - Checking doors repeatedly to make sure they're locked - Checking the stove repeatedly to make sure it's off - Counting in certain patterns - Arranging your canned goods to face the same way

Conditions – Depression Depression Severe despondency and dejection, accompanied by feelings of hopelessness and inadequacy. A condition of mental disturbance, typically with lack of energy and difficulty in maintaining concentration or interest in life.

Conditions – Depression What are the symptoms? - Feelings of sadness or unhappiness - Irritability or frustration, even over small matters - Loss of interest or pleasure in normal activities - Reduced sex drive - Insomnia or excessive sleeping - Changes in appetite — depression often causes decreased appetite and weight loss, but in some people it causes increased cravings for food and weight gain - Agitation or restlessness — for example, pacing, hand-wringing or an inability to sit still - Irritability or angry outbursts - Slowed thinking, speaking or body movements - Indecisiveness, distractibility and decreased concentration - Fatigue, tiredness and loss of energy — even small tasks may seem to require a lot of effort - Feelings of worthlessness or guilt, fixating on past failures or blaming yourself when things - aren't going right - Trouble thinking, concentrating, making decisions and remembering things - Frequent thoughts of death, dying or suicide - Crying spells for no apparent reason - Unexplained physical problems, such as back pain or headaches

Pharmaceutical Options Parkinson’s Disease Levodopa (also called L-dopa) is the most commonly prescribed and most effective drug for controlling the symptoms of Parkinson's disease, particularly bradykinesia and rigidity. Levodopa is transported to the nerve cells in the brain that produce dopamine. It is then converted into dopamine for the nerve cells to use as a neurotransmitter.

Video – Parkinson’s Disease / Dopamine

Pharmaceutical Options Depression Adapin (doxepin) Anafranil (clomipramine) Aplenzin (bupropion) Asendin (amoxapine) Aventyl HCI (nortriptyline) Celexa (citalopram) Cymbalta (duloxetine) Desyrel (trazodone) Effexor XR (venlafaxine) Emsam (selegiline) Etrafon (perphenazine and amitriptyline) Elavil (amitriptyline) Endep (amitriptyline) Lexapro (escitalopram) Limbitrol (amitriptyline and chlordiazepoxide) Marplan (isocarboxazid) Nardil (phenelzine) Norpramin (desipramine) Oleptro (trazodone) Pamelor (nortriptyline) Parnate (tranylcypromine) Paxil (paroxetine) Pexeva (paroxetine) Prozac (fluoxetine) Pristiq (desvenlafaxine) Remeron (mirtazapine) Sarafem (fluoxetine) Serzone (nefazodone) Sinequan (doxepin) Surmontil (trimipramine) Symbyax (fluoxetine and olanzapine) Tofranil (imipramine) Triavil (perphenazine and amitriptyline) Viibryd (vilazodone) Vivactil (protriptyline) Wellbutrin (bupropion) Zoloft (sertraline)

What is Deep Brain Stimulation? DBS Deep brain stimulation (DBS) is a surgical treatment in which a device called a neurostimulator delivers tiny electrical signals to the areas of the brain that control movement / or other functions.

What is Deep Brain Stimulation?

DBS Components

DBS Electrode Selection * The negative electrode exerts the therapeutic effect Lead Electrodes Bipolar Unipolar off (-) off (+) positive off (+) (-) off

DBS Electrodes (Mono/Bipolar) Bipolar stimulation can limit the spread and is beneficial to shaping field of stimulation

DBS - Stimulation Parameters Rate (Hertz) number of pulses per second Pulse Width (  sec) duration of each stimulus Amplitude (Volts) intensity of stimulation

Patient Management DBS programming goal Deliver the therapy to the brain target of interest and avoid stimulation of surrounding structures Typically, initial programming of DBS is weeks after DBS electrode implant Subsequent programming can be every 2-8 weeks for the first 3 months, and then every 3-6 months thereafter Commonly takes 6 months to obtain the best settings Many patients will require concurrent medication adjustments

Is it safe? Why do it? Offers hope to severely impaired patients when symptoms are intractable despite optimal medication and other available therapies. > 22 years of safety > 80,000 DBS Implants worldwide >3000 published articles on DBS With proper patient selection, there is improvement seen with: Standard scales/measures of disease Quality of life measures Co-morbid conditions Medication intake Chronic care costs

Is this FDA Approved? Essential Tremor – Approved in 1997 Parkinson’s Disease – Approved in 2002 Dystonia – Approved in 2003 (HDE) OCD – Approved in 2009 (HDE) Depression – Clinical Trials Ongoing - Pending Approval HDE (Humanitarian Device Exemption)

Treatment Targets Vim Thalamus: Essential Tremor Subthalamic Nucleus: Parkinson’s disease and Dystonia Globus Pallidus: Parkinson’s disease and Dystonia

Good DBS Parkinson’s Candidate Clear diagnosis of idiopathic Parkinson’s disease Atypical Parkinson’s or Parkinson’s like syndromes do not improve with surgery Good response to levodopa with levodopa challenge showing at least 33% improved UPDRS motor score Issues include one or more of the following 1) Significant Motor fluctuations and/or disabling dyskinesia 2) Disabling tremor despite optimal medication treatment 3) Medication Intolerance Stable cognition (absence of significant dementia) Realistic expectations and good family support No co-morbid psychiatric/behavioral problem Greater than 5 years of disease duration

Poor DBS Parkinson’s Candidate Significant dementia or cognitive impairment Neuropsychological compromise Untreated depression, anxiety, psychosis, or other co-morbid psychiatric illness Unable to cooperate during surgical procedure Unable to cooperate during programming visits Unrealistic expectations of outcomes Co-existing medical problems that significantly increase risks of surgery Uncontrolled heart disease, lung disease, cerebrovascular disease, uncontrolled hypertension, or diabetes. Significant structural abnormalities detected by brain MRI that would pose higher risk of brain surgery Additional features suggesting poor candidates for parkinsonism Minimal or absent response to levodopa (L-Dopa) Atypical Parkinsonian syndromes

Video – DBS Surgery

Video – DBS Surgery – Awake / Why?

Video – DBS Targets for Therapy

Video – Treatment of Depression

Neurostimulation Jeffrey R. Scott, Ph.D.