Stroke: present treatment and research part 1.

Hippocrates, the father of medicine, first recognized stroke 2400 years ago as being associated with early onset of paralysis, termed apoplexy. Johann Jacob, in 1620, was the first to recognize post mortem bleeding in stroke patients (National Institutes of Health, 1999). For unknown reasons, in the last decade incidence of stroke has been on the upswing. While it is uncertain why, excellent progress has been made in understanding the causes of stroke and treatment of stroke through physical therapy.

This article is a continuation in a series on the causes and treatment of severe disabilities. Two previous papers were published on spinal cord injury (Petrofsky 2000a, b). In this article, the history and etiology of stroke are discussed, as well as research into potential interventions to reduce the occurrence and heal the injury after stroke. Evidence-based research for present treatment is presented.

Etiology of Stroke

While stroke can affect the young, it is the single largest cause of paralysis in the elderly and is the third largest killer of adults after heart attacks and cancer. Incidence of stroke has been climbing since 1992 after a 25-year decline. In 1999 alone, the American Heart Association estimated that 600,000 Americans suffered strokes; about 100,000 of which were second attacks. There are about 4.4 million stroke survivors today in the United States (National Health and Nutrition Examination Survey III 1994, American Heart Association, 1999). Of those who have survived stroke, 70% were unable to perform their job functions; 20% needed assistance with ambulation, and 33% needed assistance for activities of daily living (ADL) (National Health and Nutrition Examination Survey III 1994, American Heart Association, 1999). Sixty percent of strokes occur in women (American Heart Association, 1999). The total cost of stroke in the United States is estimated at 43 billion dollars per year, with direct medical costs accounting for approximately 2 billion dollars per year (National Institutes of Health, 1999).

Stroke can be caused either by a clot (86%) or a hemorrhage from a ruptured blood vessel (see Figure 1) (Macdonell, 1992, National Health and Nutrition Examination Survey III 1994, American Heart Association, 1999). The hemorrhage can occur due to an artery with a weak wall which breaks open due to a crack or that simply leaks. Plaque encrusted arteries can burst when blood pressure is high, causing massive bleeding. Blood can collect in the substance of the brain (intracerebral) or in the membranes surrounding the brain (subarachnoid) (National Institutes of Health, 1999).

[FIGURE 1 OMITTED]

Figure 2, for example, is a woman who had a stroke after minor surgery. She is a professional psychologist who now can work only part time due to paralysis of one arm and one leg. She is the exception to the rule, since she has been able to return to at least limited employment.

[FIGURE 2 OMITTED]

A third type of stroke, called a Transient Ischemic Attack (TIA), looks like a stroke, but only lasts for a short period of time and then resolves (National Institutes of Health, 1999). Although new techniques and treatments in therapy have done much in the past decade to improve both clinical and home therapy, new emerging technologies may impact stroke in ways unimaginable 10 years ago. This research has taken two different paths--research that someday could lead to preventing stroke or healing the injury, and research to improve function and increase general health (see Figure 2).

Causes of Nerve Damage

Primary Damage

When blood vessels are blocked in the brain, or blood vessels rupture, circulation is no longer available to deliver oxygen to nerve cells. If blood flow is only partially blocked, then there may be few, if any, symptoms. A typical example would be partial blockage of arteries occurring due to calcium deposits. This is called anoxic anoxia (Maiese, 2001).

Recent studies show that obesity, smoking, and diabetes are among factors predisposing someone to stroke (American Heart Association, 2003). These stressors cause a generalized inflammatory response in the body by activating a DNA transcription protein, NFK Beta. This protein activates genes on DNA causing a massive release of inflammatory chemicals called cytokines and endothelial adhesion factors causing increased formation of blood clots (Mattson 1997). This generalized body inflammation makes people more susceptible to stroke. New therapies are targeting ways to block cytokines to reduce the chance of stroke (Cohen, et al., 2003). Damage to autonomic nerves with disorders such as diabetes, increase cytokines and reduce blood flow to the point where the chance of stroke is even higher (Cohen, et al., 2003).

A total loss of oxygen delivery, as with a complete blockage of the circulation, is defined as ischemic anoxia (Maiese, 2001). The area fed by the clogged artery is surrounded by an area called the ischemic penumbra, where there is poor but some oxygen delivery. This region is said to have anemic anoxia (Maiese, 2001).

Inside nerve cells, where there is a total circulatory block, a process develops called ischemic cascade (National Institutes of Health, 1999). When mitochondria no longer have oxygen with which to react, they produce toxic substances called oxygen free radicals (National Institutes of Health, 1999). One of the most common free radicals is a chemical called nitric oxide, a chemical normally released in many cells in the body. In nerve cells, it aids in control of metabolism and in killing bacteria. In smooth muscle cells, it is the intermediate controlling blood flow (Dreier, et al., 1998). When coupled with low pH (the cell becomes acid when anoxic), nitric oxide becomes cytotoxic (Maiese, 2001 ; Back, 1998; Dreier, et al., 1998). It reacts with hydrogen peroxide in the cell, producing peroxynitrate, a super oxide that damages the cell further and can fractionate DNA, attack mitochondria and membranes of other cell organelles. With the nucleus and other areas damaged, the cell membrane can no longer maintain its normal balance of ions. Toxic amounts of sodium, calcium, and other ions now enter the cell. Interior damage is made worse with high cellular calcium. Calcium, like pH, activates many free radicals and increases cellular damage.

The ischemic cell also releases glutamate and other excitatory amino acids outside the cell. Normally, these neurotransmitters are released to mediate communication among nerve cells. Released excitatory amino acids in large quantities can lead to neuronal over-excitation and damage of other nerve cells. Glutamate can damage other cells in several ways. First, it is believed that when glutamate over activates a type of glutamate receptors called NMDA receptors, calcium is allowed to enter otherwise healthy cells in large quantities. Calcium regulates many cellular processes. It activates certain proteases (calpains). Proteases destroy other proteins having regulatory roles in nerve cells. Over activation of proteases may damage important parts of the cell including the mitochondria and the nucleus. When exposed to high levels of calcium, mitochondria produce high levels of free radicals in otherwise healthy nerve cells. These free radicals damage these cells (National Institute of Neurological Diseases and Stroke, 1999). Glutamate also allows ions such as sodium to enter cells, causing swelling and potential membrane damage. A massive glutamate release may not damage otherwise healthy cells. If cells are suffering from anemic anoxia, glutamate can severely damage a cell that other-wise may go uninjured.

After stroke, the first cells began to die after 4-5 minutes. This number is small. Since treatment within a few hours can halt further damage, the implication is that the process of cell death takes hours to complete (National Institutes of Health, 1999). Recent studies show much of the initial damage can be reversed if chemicals, as described, are released in the first 6 hours of injury (Maiese, 2001).

Secondary Damage

In the next few hours, exposure to glutamate, nitric oxide, peroxynitrate, other free radicals and excitatory amino acids damages neighboring nerve cells. This is called secondary damage. Free radicals can attack lipids in the membranes (free radical lipid peroxidation) (Braughler & Hall, 1989). Nitric oxide also can damage nerve cells when reacting with other substances in the cell (Pasqualin, 1988).

These processes make survival difficult. If circulation can be restored in a few hours, these cells can be saved. If nitric oxide or glutamate can be reduced, or pH can be increased, the cell's probability of survival increases (National Institutes of Health, 1999).

Damage to blood vessels triggers inflammatory and immune responses within the affected area. Leucocytes first arriving at the site of injury mediate this process. These white blood cells move by a process called diapadesis, moving through walls of the blood vessels and into the brain causing more damage. One type of leukocyte, called monocytes, release inflammatory chemicals like cytokines, interleukins, and other agents causing the blood clot in the vessels to be more difficult for the body to retract. Over time, cells not initially damaged but with marginal blood flow and subjected to chemical or white cell attack may die (National Institutes of Health, 1999).

After about 3 days, T-cells, macrophages, and monocytes enter the central nervous system (CNS). Macrophages, monocytes, and microglia cells release regulatory chemicals that may help or hinder recovery from injury. Potentially beneficial substances released by these cells include the cytokines, TGF-beta and GM-CSF (transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor) and several other growth factors. Harmful substances include cytokines such as TNF-alpha and IL-1-beta (tumor necrosis factor-alpha and interleukin-1-beta) and chemicals such as super oxides and nitric oxide that may contribute further to oxidative damage. Further, circulation to healthy nerves in the area of damage may become more impaired after initial injury due to free radical oxidation of blood vessels serving the spinal cord or brain.

Programmed Cell Death 

The most perplexing part of understanding cell death alter stroke is a process called programmed cell death (see Figure 3)(Love, et al., 2000; Maiese, 2001). Programmed cell death (PCD), is an important part of growth and development to remodel the nervous system (Lo, et al., 1995). However, after a neurological injury, it can cause death to otherwise healthy neurons and increase the paralysis from a stroke. Research seems to indicate PCD is caused by the breaking apart (fragmentation) of DNA due to activation of an enzyme called PARP in otherwise healthy neurons (Martin, et al., 1995). Exposure of the cells to excessive nitric oxide, peroxynitrate, and some anoxia cause DNA to fragment and cells to die (Vincent & Maiese, 1999; Martin, et al., 1995; Rimon, et al., 1997). Like initial cell death in fully anoxic cells, pH must be abnormally low in these cells (Maiese, 2001). DNA is damaged directly by an enzyme called an endonuclease. There are several enzymes in this class that can be activated with nitric oxide and either low pH or high [Ca.sup.++] (Vincent & Maiese, 1999). Days after a stroke, neurons start to die due to destruction of their DNA.

[FIGURE 3 OMITTED]

Another cause of nerve cell death is from supporting cells around nerves called glia cells. Glia cells are found throughout the brain and contain gap junctions. After a variety of types of neuronal injury, glia cells produce chemicals released through their gap junctions and into the cerebral spinal fluid. Like a messenger of death, these chemicals move to the surrounding area and can kill otherwise healthy cells (Lin, et al., 1998). Cells that die may in themselves not have sustained injury. The process of glia cells promoting cell death in otherwise healthy cells is called glia fratricide. Research in using gap junction blockers such as halothane, a surgical anesthetic, may lead to a means of reducing damage after stroke.

Research to Prevent or Heal injury From Stroke

The most effective way to prevent an injury is to stop stroke from occurring. In a recent study (Jeppesen, et al., 1996) it was shown that if testosterone, a naturally occurring steroid hormone in men, drops significantly as men age, the chance of stroke increases greatly. Hormone replacement therapy in men and women has also been shown to reduce incidence of stroke in women. Estradiol and other estrogen analogs have been shown to have a neural protective effect in various parts of the brain, especially from ischemia and glutamate release (Harukuni, et al., 2001).

There has been a large body of research in recent years focusing on relationship between high cholesterol and stroke. Cholesterol is a waxy substance produced by the liver and is the basis for the production of all steroid hormones in the body. The liver is fully capable of producing all the cholesterol needed in the body (National Institutes of Health, 1999).

The high density, high molecular weight proteins are harmful for the circulatory system, therefore, leading to high risk of stroke. Lipoproteins must be controlled in the diet. The low-density lipoproteins are associated with a lower risk of stroke (National Institutes of Health, 1999). Serum cholesterol levels above 200 mg% increase the risk of stroke (National Institutes of Health, 1999).

A new class of cholesterol lowering drugs called statins inhibits HMGcoA reductase, an enzyme involved in the synthesis of cholesterol. By lowering blood cholesterol, these drugs lower the likelihood of stroke by 24% (Bucher, et al., 1998). While some of these drugs are expensive, their beneficial effects, especially when combined with a diet low in cholesterol, have had an impact in reducing the incidence of stroke (American Heart Association, 1999).

Hypertension is a leading factor causing the rupture of blood vessels and subsequent stroke. New drugs and therapies attempt to reduce blood pressure to reduce the risk of stroke. Where blood pressure is the highest, such as in the southeast United States, incidence of stroke is 2 times higher than in the rest of the country (National Institutes of Health, 1999). With hypertension alone, the risk of stroke is 4-6 times greater (National Institutes of Health, 1999). Persistently high blood pressure above 120/90 mmHg is considered a risk factor for stroke (National Institutes of Health, 1999).

If the stroke cannot be prevented, then perhaps it is possible to stop the clot from causing damage in the acute phase, the first few hours after the injury. Drugs have been developed to remove clots occurring after a stroke.

In June, 1996, the United States Food and Drug Administration (FDA) approved use of a new drug, t-PA (tissue plasminogen activator), for patients who have a stroke, (Haley, 1997). The drug Activase has shown previous success in cardiac patients (Callas, et al., 1998). It was believed that it must be given within three hours of stroke. (Brott, et al., 1992). Recent evidence from the clinical trial Proact-2 indicates the window may be as long as 6 hours (Callas, et al., 1998). Activase works by dissolving blood clots in the brain. In a multi center study, it was shown to dramatically reduce paralysis after stroke in 14% of stroke patients who were treated (Marler, 1995). Researchers who developed Activase estimated that 60% of the 400,000 Americans who have strokes are eligible for this drug; however, the drug had severe side effects in 6% of users who developed severe bleeding in the brain and died. Without the drug, 20% of the people would have died anyway. When comparing the 20% death rate without the drug to the 6% death rate with, the gain of 14% makes the drugs a good choice in lowering the overall rate of death.

Another downside to the drug t-PA is the cost. The cost per dose is as high as $2,200. However, researchers and the National Institute of Neurological Diseases and Stroke still argue for its use and safety (Haley, 1997; Marler, 1995).

Interestingly, t-PA's occur naturally in the body (Jeppesen, 1999). If the body builds up antigens to t-PA, risk of stroke increases in both men and women (Jeppesen, et al 1999). In recent studies, it has been shown that individuals, who have a normal high immunity for natural t-PA are at high risk to stroke (Zunker, et al. 1999). There are a number of research projects underway with the intent of developing antigens in the body to t-PA to reduce the risk of stroke.

Damage Can Be Limited by Experimental Drugs

One way of reducing injury following stroke is by blocking damaged cellular biochemical pathways. Damage to lipids in membranes of nerves can be minimized by glucocorticoids such as methylpregnisilone (Watson, 1998). Antioxidants such as vitamin E also can reduce injury by blocking free radical oxidation (Young, 1996; Hall, 1990). Glucocorticoids also reduce brain edema to reduce damage to the brain further after stroke. Neuroprotective agents also may be used in the future to bolster strength of nerves to secondary damage and prevent further injury (Wurtman, 1999). Another class of drugs blocks formation of one free radical, nitric oxide, and potentially reduces nerve injury further (Riddell & Owen, 1999; Moroz, et al., 1998). Nitric oxide inhibitors have been shown to reduce neuronal death, especially in blocking programmed cell death in neurons (Dreir, et al., 1998). Other drugs, such as nitroproprionic acid, have been tested which may make the brain resistant to nitric oxide. (Brambrick, et al., 2000). Other drugs try to keep pH high to block the effect of free radicals (Maiese, 2001).

One drug being tested to reduce damage following stroke is clomethiazole. This drug is neuroprotective and attempts to limit damage if administered within 12 hours after stroke (National Institute of Neurological Disease and Stroke, 1999). It is a GABA (gamma amino butyric acid) agonist. GABA alters chloride conductance and blocks the effects of glutamate, which damages cells when anoxic. Currently, clomethiazole is being studied in both stroke and spinal cord injury models to determine if beneficial effects outweigh side effects (Lutsep & Clark, 1999, Farooque, et al., 1999).

Another member of this class of neuroprotective agents is Citacoline. This drug is administered for 12 weeks following stroke. It appears to have neuroprotective benefits and works as an aid to repair of neurons (Wurtman, 1999). The drug appears to have neuroprotective, neurorepair and neurocognitive effects and works by stabilizing cell membranes and reducing free radical generation (Clark, et al., 1999).

The FDA has recently approved a new drug to reduce the chance of a second stroke in patients (FDA, 1999). The new drug, Aggrenox, is a combination of aspirin and dipyridamole. Aggrenox was tested on 6602 patients and reduced risk of stroke by 36% for first strokes and 24.2 % for second and third strokes (FDA, 1999). The drug works by inhibiting platelets from forming clots, thereby potentially reducing the risk of a second attack (Hervey & Goa, 1999).

A number of different centers are testing hypothermia after stroke to reduce damage to the brain. Recent studies show that hypothermia must be accomplished within 10 days after stroke. The body is cooled to between 89 and 91[degrees]F Cooling is kept at this level for 24 hours. The procedure is being tried for patients with both thrombus and hemorrhagic stroke (Huang, et al., 1999; Kirkpatrick, 1999).

Hyperbaric oxygen is another form of therapy being investigated after stroke. This technique places the patient in a chamber with pressurized oxygen to allow more oxygen to reach damaged brain tissue. As described, there is an ischemic penumbra around poorly oxygenated brain cells. It is believed that supplying more oxygen to these areas may reverse some of the symptoms of stroke. While there is controversy over use of hyperbaric oxygen, a recent study has shown neurons dormant after ischemia to the brain regained blood flow and function after treatment with hyperbaric oxygen (Neubauer, 1998).

Hyperbaric oxygen is used to treat stroke around the world. While some patients respond well, others show little change. This technique remains useful, but the jury is still out as to why it only works on some people.

Where nerve cells have been destroyed after a stroke, regeneration of nerves in the brain may be possible in the future. Skin cells and other cells in the body regenerate. Nerves in the central nervous system, however, have shown little ability to regenerate until recent years (Z'Graggen, et al., 1998). For cells to regenerate they must be able to grow axons to the fight target cell and they must make functional contact to the target cell through a specialized structure called a synapse. To promote proper growth, the nerve cells need a combination of nerve growth factors and neurotrophic substances to direct the cell in the proper direction (National Institute of Neurological Disease and Stroke, 1996).

Regeneration is limited in the central nervous system due to the release of proteins in the myelin sheath surrounding nerves in the central nervous system which inhibit nerve growth. These inhibitory factors are controlled by a gene that has been recently discovered (National Institute of Neurological Disease and Stroke, 1996). While this benefits the nervous system by preventing new nerve growth late in human development, it also prevents regeneration (Bunge, 1991). Studies have shown the use of substances that block anti nerve growth factors allow nerves in the spinal cord to begin regeneration. In fact, in lab animals, this process has already led to full recovery following spinal cord injury (Werner, et al., 1998). Although these experiments were conducted on laboratory animals, human trials will take place at a future date. However, early results on lab rats were promising.

Another possibility is to graft neural tissue into the brain. Many studies have been conducted but have failed. Cells from other bodies are rejected by the host's immune system. To avoid this complication, genetic engineering may help allow DNA to be modified in nerve cells and cell lines to be laid out to allow nerve cells to differentiate and move toward their targets. The fact that cells are modified to be nerve cells should reduce rejection rate by the body. Recent research has shown that some adult cells in the central nervous system can divide and differentiate when placed in the proper environment (Tatagiba, 1997). Powerful drugs used in transplanting organs must be used to reduce incidence of rejection. The time may come in the future when the same may be feasible in humans (Neural Grafting, 1996). Tissue transplants have already seen immediate are effects in patients with Parkinson's disease, but results only seem to last approximately six months. Use of neural tubes in the spinal cord and grafting tissue allow nerve growth, yet little functional contact has been made. Further research in this area is needed.

Cells that are not rejected, and grow bridges, are from fetal tissue. If these cells are successful in curing stroke, a host of ethical issues must be addressed in the future.

Classification of Stroke and Type of Injuries

Symptoms of stroke vary with the area of the brain damaged and etiology of damage. If atherosclerotic plaques and hypertension lead to stroke, plaques branch into many arteries in the brain. Before the full stroke, there may be mini strokes (transient ischemic attacks), which last for short periods of time (Umphred, 1995). Blood clots eventually invade the arterial tree in the brain and, sometimes over hours, occlude an artery before full symptoms of stroke occur.

If an embolus breaks free from another part of the body or if there is a blood vessel rupture in the brain, the stroke is rapid and symptoms express themselves quickly. Exact symptoms depend on the area of the brain damaged.

Damage to the brain is often focused in one area. There are numerous arteries supplying the brain, and often a stroke is limited to the area served by that artery. If large arteries feeding both sides of the brain are involved, symptoms are seen on both sides of the body. Generally, smaller arteries are blocked only affecting one side of the body. Another factor is amount of collateral circulation in the part of the brain affected by a stroke. Collateral circulation refers to the notion that many areas of the body receive blood from several arteries, so if one is blocked, others still supply some blood. If there is good collateral circulation, effects of a stroke will be slight, but if there is poor collateral circulation, effect of a stroke is more severe.

One of the most obvious disorders associated with stroke is hemiplegia (paralysis on one side of the body). This is a common symptom of stroke, but only occurs if the artery to the motor centers on one side of the brain is blocked. Strokes can occur affecting other parts of the brain. But if a stroke, for example, affected the left motor cortex of the brain, then the right side of the body would be paralyzed. Along with this paralysis is the inability to feel on that side of the body, or at least some loss in sensation (sensory impairment). While movement can occur without the senses working properly, senses are used for coordination and fine tuning of movement making retraining in rehabilitation challenging after a stroke.

In the first few days after such a stroke, there is usually paralysis (i.e., lack of tone in the affected limb). As recovery progresses, there is a return of movements in some muscles, but inefficient patterns of control of the joints begins to develop causing poor balance and alignment of the body. The shoulder, for example, may hang (sublux) on the affected side causing compensation to correct for gravity on the other shoulder to keep the body vertically aligned. If a leg is paralyzed, hip muscles increase activity to lift the leg (hip flexors) excessively high with each step rather than the normal swing in gait used when the leg muscles are not paralyzed involving contraction of knee and ankle muscles.

The most severe problems that can occur are those of abnormal co-contraction of muscles. In many people who have a stroke, muscles such as the ones that move the elbow contract at the same time. For this joint, for example, if the biceps (flexor) and triceps (extensor) contract together, there can be no movement at the elbow. The same occurs at the shoulder and fingers causing the shoulder to be elevated, the elbow to be left flexed, and fingers flexed at rest. This hypertonic muscle activity and loss of coordinated control leaves the shoulder fairly useless.

The same can occur in the lower extremity. There can be mass flexion of muscles in a leg when the person attempts to walk. Lack of coordination between extensors and flexors causes severe compensation from other muscles, therefore resulting in severe deviations during ambulation. As the person tries to use the upper or lower limb, there can be an increase in tone in other muscles. In an attempt to walk, the affected arm may contract heavily. When this is coupled with sensory deficits, matters are even more severe. The person may be able to feel, but not localize from where the feeling is coming. The challenge in rehabilitation is to re-educate the motor system to break these patterns of synergy as much as restore purposeful movement.

Finally, a stroke may affect other areas of the body, as well. If the vertebral artery is blocked, there may be a loss of hearing or balance. Other arteries may cause loss of vision or memory. In short, symptoms may be minor or very severe with a stroke, and the challenge in rehabilitation is to allow as much recovery as possible. While there is great hope for the future for patients who have a stroke, once the paralysis occurs, today there are many techniques in physical therapy that can increase independence and the ability to adapt and live with paralysis. The second article in this series deals with present therapeutic techniques for stroke patients.

Definitions

Anoxic anoxia--partial blockage of blood vessels in the brain due to calcium deposits in arteries.

Clomethiazole--a drug that can protect nerve cells from damage after a stroke.

Glutamate--chemical released by nerve cells to communicate with other nerve cells.

Hemiplegia--paralysis of one side of the body.

Hemorrhage--a break in a blood vessel releasing blood into tissues such as the brain.

Ischemic cascade--a series of events that takes place in a nerve cell starting with lack of oxygen resulting in death of the nerve.

Monocytes--a type of white blood cell that helps fight infecting organisms.

Nitric oxide--a chemical produced in the body that is used to regulate blood flow, oxygen use, and kill invading bacteria.

t-Pa (tissue plasminogen activator)--a naturally occurring substance in the body that helps break up blood clots

Transient ischemic attack (TIA)--spasm in a blood vessel in the brain that brings on symptoms of a stroke, but heals over time.

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Jerrold Scott Petrofsky holds a BS degree in Biology, as well as a BS in computer engineering technology. He holds a PhD in physiology, an A J.D. and two honorary Doctorates. He is currently a professor at Loma Linda University, and holds the rank of Distinguished Professor of Research at Azuza Pacific University. Presently he is involved in basic science and clinical research at both Universities. Afsaneh Kazemi Petrofsky is a graduate of California State University at Long Beach with a science degree in Physical Therapy. She has been practicing for over 10 years. She began her career as head of out patient rehabilitation at the University of California in Irvine, CA. During her career at UCI, she developed protocols for the treatment of myofascial conditions, wound and burn conditions. She is presently conducting research as a co-investigator on a grant to reduce Trendelenburg through the use of EMG. Salameh Bweir graduated with a BS in Biology from Jordan University in Jordan. He has over 16 years of experience as a Physical Therapist and is the Director of the Physical Therapy Department in King Housein Medical Center in Jordan.