STROKE

An Integrative Oriental Medicine Approach To Treatment & Management

J. E. Williams, OMD, L.Ac., FAAIM

Course Objectives

1. Understand clinical aspects of stroke.

2. Understand place of acupuncture in stroke rehabilitation.

3. Learn evidence-based approach to stroke treatment.

4. Learn safe and effective integrative medicine model for stroke recovery.

5. Establish outcome model for stroke therapy.

Course Outline

• Physiologic basis for stroke• Role of OM in stroke rehabilitation• Evidence for acupuncture in stroke therapy• Chinese medicine view of stroke• Treatment methodology• Drug interactions• Demonstrations and practicum

INTRODUCTIONStroke Prevention, Treatment, and Recovery

Incidence of Stroke

• New or recurrent strokes affect about 780,000 Americans every year.

• Someone in the U.S. has a stroke every 40 seconds. • 4th leading cause of death in the U.S.• 4% of U.S. adults will have a stroke. • The annual cost of stroke care is predicted to increase from

$71.55 billion in 2010 to $183.13 billion.• Stroke incidence is projected to increase the most among

Hispanic men between now and 2030, and the cost of treating stroke in Hispanic women is expected to triple.

• 90% of stroke patients have residual disability.• While age is the major risk factor, people who have a stroke are

likely to have more than one risk factor.

Demographics

• Age: 72% are over age 65• Gender: More common in men, but women account for

about 6 in 10 stroke deaths.• Race: African-American men have more than twice the

incidence of stroke than Caucasians. Hispanics and blacks not only have a higher rate of stroke incidences, but experience worse outcomes.

STROKE PREVENTION

CONTROLLABLE RISK FACTORS:

High Blood Pressure Atrial Fibrillation Diabetes Smoking High Cholesterol Metabolic Syndrome Atherosclerosis Circulation Problems Alcohol Inactivity Obesity Anabolic Steroid Use

CT scan slice of the brain showing a right-hemispheric ischemic stroke.

MAJOR RISK FACTORS

• Hypertension• Atrial fibrillation• Diabetes• Hyperlipidemia• Symptomatic carotid

stenosis• Migraine with aura

Atrial Fibrillation (AF)

• Rapid, irregular artial rhythm – may be episodal or continuous:• Palpitations• Weakness, effort intolerance• Vague chest discomfort• Dyspnea• Presyncope

• Diagnosis is by ECG, and blood tests (thyroid function, glucose, lipids)• Main Risk: stroke (7%)• Other Concerns: lower cardiac output (10%)• Complicated by rheumatic valvular disorder, hyperthyroidism,

hypertension, diabetes• Etiology: hypertension, cardiomyopathy, valvular disorders,

hyperthyroidism, and binge alcohol drinking (“holiday heart”)• Treatment: heart rate control with drugs, prevention of embolism with

anticoagulants, cardioversion procedure

Definition

Sudden onset of a neurologic deficit from a vascular mechanism:• 85% ischemic• 15% primary hemorrhage

(subarachnoid and intraparenchymal)

• Transient ischemic attack (TIA) “mini stroke”

Figure 1a.  (a) Schematic of brain involvement in acute stroke shows a core of irreversibly infarcted tissue surrounded by a peripheral region of ischemic but salvageable tissue

referred to as a penumbra.

Srinivasan A et al. Radiographics 2006;26:S75-S95

©2006 by Radiological Society of North America

Pathophysiology & Clinical Features

• Most often due to embolic occlusion of large cerebral vessels in the heart, aortic arch, or carotid arteries.

• Abrupt and dramatic onset with focal neurological symptoms.

• Rarely experience pain.• Presentation is based on area of brain involved.

TYPICAL SIGNS AND SYMPTOMS

• Abrupt onset of hemiparesis, monoparesis, or quadriparesis• Acute hemisensory loss• Complete or partial hemianopia, monocular or binocular visual

loss, or diplopia• Visual field deficits• Dysarthria• Ataxia• Vertigo• Nystagmus• Aphasia• Sudden decrease in the level of consciousness

Conditions That Mimic Stroke

• Brain tumors• Seizures• Migraine• Other conditions (viral or bacterial infections,

gastrointestinal distress, thyrotoxicosis)

Flow chart shows an acute stroke imaging protocol

Srinivasan A et al. Radiographics 2006;26:S75-S95

©2006 by Radiological Society of North America

Ischemic Stroke

IMAGING STUDIES

• Non-contrast CT scan of the head within first few hours• Diffusion-weighted MRI also used within minutes after

onset• Other imaging studies:

• Angiography• Ultrasonography• Echocardiography

STROKE THERAPIES

• Thrombolytic therapy: Thrombolytics restore cerebral blood flow among some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic deficits.

• Antiplatelet agents: The International Stroke Trial and the Chinese Acute Stroke Trial (CAST) demonstrated modest benefit from the use of aspirin in the setting of acute ischemic stroke.

• Mechanical thrombolysis: Involves the endovascular treatment of acute ischemic stroke.

• Neuroprotective therapies: Many under investigation but few have shown benefits.

Drugs Used for Stroke

• Anticoagulant agents: Not used for hemorrhagic stroke and studies do not support use in acute ischemic stroke

• Thrombolytic agents: Tissue plasminogen activator (tPA) for ischemic stroke.

• Antiplatelet agents: Aspirin – up to 325 mg per day• Neuroprotective agents: Lots of interest but no approved

therapies - http://emedicine.medscape.com/article/1161422-overview#aw2aab6b3

Drugs That Can Cause Stroke

• Sumatripan, the migraine drug (Intensive Care Med, 1995; 21: 82-3). • Beta blockers (Revist Clinica Espan, 1993;192: 228-30). • Nefedipine (causing cortical blindness) (BMJ, 1992; 305: 693). • Chemotherapy or hormones given during chemotherapy (Am J Clin Onc, 1992; 15:168-

73). • Contraceptive pill (Acta Neurol Belg, 1992;92: 45-7). • Oral anticoagulant therapy (The Lancet, 1991; 338: 1158). • Nasal decongestants (J Neurol, Neurosurg & Psychiatry; 1989; 52: 541-3). • Blood pressure lowering drugs (Med J Australia, 1987; 146: 412-4). • Phenylpropanolamine, a drug available over the counter in weight loss, nasal congestants

and cold preparations (Am J Emerg Med, 1987; 5: 163-4). • Recreational drugs, like Ecstacy, cocaine, and methamphetamines (European Neuro, 1995;

35: 193; South Med J, 1995; 88: 352-4; Europ Neuro, 1994; 34: 16-22). • Anabolic steroids (Neuro, 1994; 44: 2405-6). • Streptokinase/subcutaneous heparin therapy, combination therapy, (Circulation,1995; 92 :

2811-8) and recombinant tissue type plasminogen activator (Circulation;1991; 83: 448-59).

• Anticoagulant medication (Arch of Neuro, 1985; 42: 1033-5). • Ingesting hydrogen peroxide (Stroke; 1994;25: 1065-7).

Hormone Replacement

• Reduces risk of coronary heart disease (Hodis HN, Mack WJ 2013)

• Estrogens offer neuroprotective effects (Liu R, Yang SH 2013)

• N Engl J Med. 2012 Jun 14;366(24):2316-8. doi: 10.1056/NEJMe1204769.Hormonal contraceptives and arterial thrombosis--not risk-free but safe enough. Petitti DB.

• Lancet Neurol. 2012 January; 11(1): 82–91.Menopause and Stroke: An Epidemiologic Review. Lynda Lisabeth, PhD and Cheryl Bushnell, MD

• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615462/

Lab Tests

• Lipids – VAP profile• Glucose• Hemoglobin A1c• Homocysteine• C-Reactive Protein,

cardiac/hsCRP• Lipoprotein(a)• Fibrinogen• lipoprotein phospholipase

A2 (Lp-PLA2) - PLAC® Test

• MTHFR gene mutations

Cardiovascular Risk Marker Profile

Cholesterol

Triglycerides

Low-Density Lipoprotein (LDL)

High-Density Lipoprotein (HDL)

Glucose

Hemoglobin A1c

Homocysteine

C-Reactive Protein

Vitamin D, 25-Hydroxy

Vitamin B12

Vitamin B-12 (cobalamin) plays a role in making DNA, and helps keep nerve cells and red blood cells healthy. It is necessary for managing homocysteine levels in the body.

Iron

VAP Lipid Profile

• Comprehensive lipid analysis• Provides stratified lipid-associated CVD risks• Supports personalized preventative care

Lipoprotein(a)

RISK VALUESDesirable < 14 mg/dL (< 35 nmol/l)

Borderline 14 - 30 mg/dL (35 - 75 nmol/l)

High 31 - 50 mg/dL (75 - 125 nmol/l)

Very high > 50 mg/dL (> 125 nmol/l)

LabCorp Reference Interval: <75 nmol/LAtherotech Desirable Level: <10 mg/dL (= “optimal” level)

Fibrinogen

• Fibrinogen is a protein produced by the liver that helps stop bleeding by encouraging blood clot formation.

• Association between elevated fibrinogen levels and increased risk for atherosclerotic vascular disease.

• Reference interval: 193−507 (LabCorp)

PLAC® Test http://www.plactest.com/

• Predicts risk of acute heart attack or stroke more accurately than do traditional markers of cardiovascular risk.

• Measures levels of the enzyme lipoprotein phospholipase A2 (Lp-PLA2).• Lp-PLA2 triggers a chain of events resulting in endothelial dysfunction in the

blood vessel wall that sets the stage for atherosclerosis, plaque accumulation, and rupture.

• Lp-PLA2 is found in high concentration in atherosclerotic plaques that are ready to rupture, causing heart attack or stroke.

• Lp-PLA2 reflects inflammation in the atherosclerotic plaque and its activity is associated with macrophages.

• Levels of Lp-PLA2 rise in individuals at risk for acute heart attack and stroke.• As sensitive and more specific for acute cardiovascular risk than other more

widely used cardiovascular risk markers.• To monitor response to diet, statins, and other treatments.

Normal range < 200 ng/dL

MTHFR Gene Mutation

• The official name of this gene is “methylenetetrahydrofolate reductase.”

• At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria.

• Most common 2 mutations are A1298C and C677T each refer to variants in a MTHFR gene in our DNA.

• Around 30% of Europeans, 10% of Africans, and 50% of Chinese people have the C677T version of the MTHFR gene.

http://www.youtube.com/watch?v=QRHif2aVPvw#t=64

Solving stroke one piece at a time.

Putting the Pieces Together

CHINESE MEDICINEHow the ancients viewed stroke

Degree of Attack

• Mild: Wind attacking network channels – Zhong Luo

• Moderate: Wind attacking channels – Zhong Jing

• Severe: Wind attacking organs – Zhong Fu & Zhong Zang

TCM Etiology

• Yin deficiency of liver and kidney failing to control yang: lack of qi and blood, and too much rising heat Age plays a significant role

• Explosive anger damaging liver yin• Chronic stress and emotional repression causing liver qi

stagnation, transforming to heat, stirring up liver wind• Excess alcohol and fatty foods• External “wind” attacking channels and vessels• Excess yang constitution associated with hyperactivity of

liver yang

Point Selection

• Classic Basic Points:• Ren Zhong GV26• Jia Che ST6• Bai Hui GV20• He Gu LI4

• For “Tense” Type:• GV26 + GV20• Bleed 12 “well points”• Yong Quan KI1

• For “flaccid” Type:• CV4, 6, 8, 17• ST36• GV4, 26, 20• BL 15, 23

Dr. Shi Xue-min’s Points

• PC6, GV26, SP6• Neiguan confluent point 8 extra meridians and luo point of

the PC channel• Renzhong is the confluent point of the GB channel, controls

yang of the whole body• Sanyinjiao nourish liver and kidney

• Additional Points: HT1, LU5, BL40, LI4, GB20, TH17, GB12

Variation of Strategies

• Based on affected side• Based on associated

organ and/or meridian dysfunction

• Scalp needling• Local area needling• Electro-stimulation• Point selection of

different masters

ACUPUNCTURE FOR STROKEFrom Art to Science

Acupuncture Contradictions

• No known contradiction for using acupuncture for stroke patients after initiation emergency measures.

• Precaution with anticoagulants and antiplatelet drugs. • Precaution in older and very weak patients.

Research: PubMed 547 Citations for Acupuncture and Stroke

• Clinical experience is favorable for improving stroke patient outcomes.

• Patient reports are favorable for improvement in wellbeing, anxiety, and pain in post-stroke recovery.

• Earlier studies were favorable for use of acupuncture to treat post-stroke symptoms and to support recovery

• Recent studies do not support efficacy of acupuncture for sub-acute stroke or post-stroke recovery. (Sze FK, et al 2002)

• Acupuncture may help motor recovery in chronic stroke survivors. (Zhang H, et al 2013)

Figure 4. PET (positron emission tomography) images reveal an abnormal pattern of neural activation (right) during a finger manipulation task (see Figure 3) performed by the stroke-affected hand of patients who had experienced a stroke to the motor cortex in one hemisphere of the brain (lesion). Abnormal neural activity (in the premotor cortex and the supplementary motor area) on the unlesioned side of the brain suggests that these areas have learned to compensate for the damaged motor cortex on the lesioned side. Performance of the task by the unaffected hand shows a normal pattern of activity (left).

http://www.americanscientist.org/my_amsci/restricted.aspx?act=pdf&id=2900445295912

Brain Plasticity and Recovery from Stroke 200

Brain Plasticity Theory

Brain Plasticity & Neurorestorative Therapies in Stroke Recovery

Brain Plasticity and Stroke RehabilitationThe Willis Lecture. Stroke. 2000; 31: 223-230 Barbro B. Johansson, MD, PhDhttp://stroke.ahajournals.org/content/31/1/223.long

• Enriched environmental setting including more social interactions• Growth factors: fibroblast growth factor (bFGF), nerve growth factor (NGF),

insulin growth factor-1 (IGF-1)• Brain immune cell modulating factors • Neuroregenesis and stem cells

Auton Neurosci. 2010 Oct 28;157(1-2):9-17 Epub 2010 May 7.Neurotrophins and acupuncture. Manni L, et al

The aim of this review is to report recent findings and ongoing studies on the effects of acupuncture on endogenous biological mediators, in particular on neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Acupuncture is a therapeutic technique and is a part of Traditional Chinese Medicine (TCM).

Neurol Res. 2008 Nov;30(9):985-9. The influence of electro-acupuncture on neural plasticity in acute cerebral infarction. Ren L, et al.

To observe the effect of electro-acupuncture (EA) on dendritic spine and ephrin-A5 and to investigate the action of EA on neural plasticity after acute cerebral ischemic infarction. It is possibly the regulation of the ephrin-A5 expression by which EA treatment improves the neural plasticity at the peri-infarct cerebral cortex in acute cerebral ischemia rat. There may be a time window in EA treatment for acute cerebral ischemia.Acupuncture & Brain Plasticity

Evid Based Complement Alternat Med. 2012. Effects of Electroacupuncture at Head Points on the Function of Cerebral Motor Areas in Stroke Patients: A PET Study. Fang Z, et al.

Positron emission tomography (PET) is used to observe the cerebral function widely and is a good method to explore the mechanism of acupuncture treatment on the central nervous system. By using this method, we observed the cerebral function of 6 patients suffering from ischemic stroke after receiving EA treatment at Baihui(GV20) and right Qubin(GB7). We concluded that EA was very helpful for the cerebral motor plasticity after the ischemic stroke.

• “Glucose metabolism changed significantly on primary motor area (M1), premotor cortex (PMC), and superior parietal louble (LPs)”.

INTEGRATIVE THERAPIES

Healthy Lifestyle

• Plant-based, anti-inflammatory diet• Regular exercise• Stress management

• “Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing ischemic stroke.”

• Neurologia. 2012 Epub 2011 Sep 3.• Guidelines for the preventive treatment of ischaemic stroke and

TIA . Update on risk factors and life style.

Dr. Weil’s Anti-Inflammatory Food Pyramid

Foundational Nutritional Supplements

• Omega-3 Fatty Acids, high EPA 1,000 mg • Folic Acid as L-5-Methyltetrahydrofolate 400 mcg• Alpha Lipoic Acid 200 mg• Vitamin B6 as Pyridoxal-5’-Phosphate (P5P) 50 mg• Vitamin B12 as methylcobalamin 1,000 mcg• Vitamin E, high gamma with mixed tocopherols 400 IU• Selenium as selenomethionine 200 mcg• Coenzyme Q10 250-600 mg• Multivitamin and mineral with polyphenols

Antioxidants

“...reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a common underlying mechanism of many neuropathologies.”

Curr Med Chem. 2008;15(4):404-14.Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging.Slemmer JE, Shacka JJ, Sweeney MI, Weber JT.

Antioxidant reduce cell damage by countering the dangerous effects of free radicals produced when the body processes oxygen:

• Vitamins C, E, A• Betacarotene• Glutathione• SOD

Lowering CRP

• Wild blueberry (vaccinium angustifolium)

• Cranberry (vaccinium macrocarpon) Pomegranate (punica granatum) 50 mg whole fruit extract standardized to contain 40% punicosides

• Lipolytic Enzymes• Serrapeptase, Nattokinase, Lipase

• Protease Enzymes• Protease (derived from Serratia, B. subtilis

and A. oryzae)

Specialized Supplements

• Lumbrokinase 600,000 IU (40 mg): 1-2 capsules daily with or without food

• Serrapeptase Enzyme (Peptizyme SP®) 10 mg (providing 20,000 units of proteolytic enzyme activity): 1 capsule three times daily without food

• Nattokinase NSK-SD (soy) 2000 FU (100 mg): 1 soft gel capsule twice daily with or without food

Use with caution. May be contraindicated with concurrent Coumadin use.

Benefits of Exercise

• Elevated Aerobic Fitness Sustained Throughout the Adult Lifespan Is Associated With Improved Cerebral Hemodynamics (2013)

• Phys Ther. 2013 Promoting Neuroplasticity for Motor Rehabilitation After Stroke: Considering the Effects of Aerobic Exercise and Genetic Variation on Brain-Derived Neurotrophic Factor. Mang CS, Campbell KL, Ross CJ, Boyd LA.

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ACUPUNCTURE QUALITY MONITORS: HealthSouth

Help Patients Prevent All Forms of Cardiovascular Disease

“Up to 80 percent of all strokes can be prevented—start reducing

risk now.”

Clinical Strategies

• Evaluation & Diagnostics• Management of Risk Factors: lower blood pressure,

lower homocysteine, lower CRP, improve vitamin D3 status, normalize thyroid function

• Lifestyle Modifications: stop smoking, reduce alcohol or stop drinking, regular moderate exercise, plant-based anti-inflammatory diet

• Acupuncture• Consider herbal therapies

Case Study: StrokePage 66

40-year-old male executive, non-smoker, healthy diet, black belts in karate and hapkido. Only one of two professional football players to suffer a massive heart attack during a game. Fully recovered.

Onset was severe headache, unrelenting for 6-8 hours. Tried acupuncture without relief. MD prescribed prednisone without relief. At 12 hours, numbness in thumb and first finger. Rapidly progressed to hemiparesis. ER diagnosed ischemic stroke.

Patient requested acupuncture in hospital, which was denied. Within a week after discharge, he was brought to my office in a wheel chair. Treatments were every other day for one month, then twice weekly for three months. Patient made consistent and steady progress. Within two years, achieved 95% full use of upper limbs, and 100% use of lower limbs and speech. Slight memory impairment persisted, but by the end of four years he had full normal cognitive ability.

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Integrating Therapies

Integrative Medicine including

Acupuncture

Physical Medicine

Western Emergency Medicine