Question: "Recently I was reading about the University of Miami's work with biofeedback in the treatment of stroke. How useful do you think this is in the overall treatment of stroke?"

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Question: "How helpful is the drug Aricept with memory loss in stroke?"

Answer: Aricept is a medication that has been approved for use in Alzheimer's disease. It acts by increasing the level of a naturally occurring chemical neurotransmitter, acetylcholine. Its effectiveness in Alzheimer's disease has been modest, with a minority of patients experiencing a minor improvement in mental functioning. Its use in stroke is less well studied. Some doctors have begun to try it in the setting of dementia due to multiple small strokes, but no one has reported major benefit in this setting. Fortunately, the drug itself seems relatively free of serious side effects.

Answer: The reported incidence of clinical depression ranges from one-quarter to two-thirds of stroke patients. Understandably, a grievous loss of neurologic function may be sufficient cause for depression, but beyond that, there is evidence that stroke in certain regions of the brain may give rise to depression more often than stroke in other areas. As a generalization, patients with left-hemisphere strokes are more prone to depression than patients with right-hemisphere strokes.

Stroke-related depression is important to recognize, because it may adversely affect one's functional recovery. For example, in a recent study of patients with comparable neurological deficits, depressed patients were more impaired in physical activity and language functioning than were the non-depressed, even two years after the event.

Treatment of depression after stroke must be individualized, but the best results are achieved by a combination of anti-depressant medications along with the loving support and encouragement of friends and family.

Answer: The thalamus is an important switching station for sensory information in the central nervous system. Damage to this area (or in the nearby parietal lobe) can lead to a distortion of sensory signals such that the brain perceives the incoming information as pain rather than as, say, touch or pressure or vibration. Stroke is probably the most common cause of thalamic pain syndrome. The disorder is difficult to treat. Commonly-used medications include anti-epileptic and anti-depressant agents, but these are often ineffective. I am not aware of any controlled studies using acupuncture in this setting. In some studies, acupuncture has been reported to improve functional recovery from stroke in terms of balance, mobility skills and activities of daily living. I cannot be optimistic that it would help thalamic pain, but I think there is little harm in trying it. Most patients with this sort of problem will be best served by referral to a multi-disciplinary pain clinic, where a variety of treatment approaches, including acupuncture, may be considered.

Answer: Frozen shoulder, adhesive capsulitis in medical jargon, is a condition that arises in association with prolonged immobility of the arm. Its incidence peaks after age 50, and women are more commonly affected than men. Frozen shoulder occurs in a variety of conditions, but stroke is clearly a predisposing factor when it causes a loss of strength that inhibits regular arm motion. The pathological mechanism by which frozen shoulder develops is unclear, though it appears to be an inflammatory process. Diagnostic tests are usually negative, but x-rays, arthrograms, MRI and bone scans may be useful in ruling out problems resembling this disorder.

Frozen shoulder generally has three phases: 1) pain and increasing stiffness; 2) decreased pain, but marked stiffness and limitation of shoulder movement---hence, the term "frozen"; 3) gradual recovery or "thawing" with improvement of motion and reduction of pain. Each phase lasts from several to many months. Recovery in less than six months is rare, but most patients eventually regain full motion of the shoulder.

Treatment usually involves physiotherapy and medication. Local corticosteroid injections, nerve blocks, and transcutaneous nerve stimulation may be useful. In refractory cases, manipulation of the shoulder under general anesthesia is sometimes used, but surgery is usually not indicated.

Answer: Neurological deficits caused by stroke are maximal about the time of stroke onset. Nearly all stroke survivors improve to some extent in the weeks and months that follow. Yet, how the brain recovers after stroke is not well understood. Uninjured brain cells may "take over" functions that were previously performed by the damaged cells. The basis for such an adaptation is thought to be the same as that underlying normal learning and memory, processes that depend upon a physiological phenomenon called long-term potentiation (LTP). This involves a strengthening of the communication effectiveness between nerve cells.

Nerve cell communication, in turn, depends on neurotransmitters, and these are affected by amphetamine. In laboratory animals, amphetamine enhances LTP, memory retrieval, and recovery from brain injury. Thus, it is attractive as an adjunct treatment in patients recovering from a stroke. Other agents also accelerate recovery from brain injury in the experimental setting. These include norepinephrine, caffeine, and L-dopa. In fact, more than 150 drugs have been reported as potentially beneficial to stroke patients. To date, however, none has been proven to be effective by careful clinical study.

The dark side of this picture is that medications may have detrimental effects on recovery from brain injury. Among the potentially harmful agents are: benzodiazepines, haloperidol, prazosin, clonidine, phenytoin and phenobarbital. For now, most authorities recommend that drugs be stopped whenever medically possible during the recovery period. With further research, we may one day be able to provide rational and effective combinations of therapy for patients rehabilitating from stroke and other causes of brain injury.

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Question: How long does recovery from stroke take? Can it continue for more than six months?

Answer: The greatest degree of recovery from stroke occurs in the first six months. It is also during this period that rehabilitation is most helpful. I think it is fair to say, however, that recovery can continue for a much longer period. Clearly, learning is a life-long process, and recovery from stroke is in a sense a kind of re-learning how to do things, perhaps in a different way. Just as each of us can continue to learn new ways of coping with life's frustrations, so stroke survivors can continue indefinitely to learn ways of working around their limitations.

It is important to instill this attitude in patients during the first six months. Thereafter, much of the work can probably be done by the patient and family, independent of formal rehabilitative therapy. From a psychological perspective, stroke survivors should be encouraged never to give up or to stop trying. If they do, the belief that they will never get any better becomes a self-fulfilling prophecy.

Answer: The first successful transplant of a human organ, a kidney, was done in 1950. Since then, organ transplantation has become relatively common. About 20,000 a year are done in the United States. Besides the kidney, transplantable organs and tissues include heart, lung, liver, pancreas, cornea and bone marrow. Transplantation of brain tissue has lagged behind. This is partly because a basic ethical requirement for transplantation is that either the donor has an organ to spare (in the case of paired organs like kidneys) or the donor is brain dead and no longer in need of the vital organ in question. Each potential donor has only one brain and transplanting dead tissue after brain death hasn't seemed very likely to help anyone.

Brain tissue transplantation has been done in people with Parkinson's disease, an illness that afflicts restricted portions of the brain in a fairly regular manner. Final judgment about the safety and effectiveness of this procedure is still pending, but ethical concerns have been raised, as the tissue transplanted typically comes from aborted fetuses. In June of this year, researchers at the University of Pittsburgh circumvented these ethical concerns in performing a new type of transplant on a stroke victim.

Rather than transplanting formed tissue, millions of nerve cells were injected into a restricted area of damage deep inside the brain. This was done via a needle inserted in a small hole drilled in the skull. The cells were not from aborted fetuses. Rather, they were produced in the laboratory. They were derived from a rare testicular cancer that had been removed from a young man. The cells in this kind of cancer are similar to those in an embryo. Remarkably, treatment of the cells with retinoic acid causes them to develop into nonmalignant mature nerve cells.

This is clearly preliminary work. The Pittsburgh researchers plan to do the procedure in 12 patients with a severe stroke in the area of the brain called the basal ganglia. It will be months before they make a final report. It will be years before such a procedure could be widely available. To date, however, results in animal models are encouraging.

Answer: Urgent treatment of an acute stroke with t-PA, a clot-dissolving medication, has the potential to completely prevent the permanent brain damage that a stroke might otherwise cause. Unfortunately, it also has the potential to cause serious, even fatal bleeding within the brain. In a large clinical trial at leading stroke centers around the country, t-PA's benefit/risk ratio seemed favorable. For treated patients, the absolute increase in no-disability outcomes was about 12%, while the absolute increase in significant brain hemorrhage was about 6%. Even allowing for the greater number of hemorrhages, treated patients were less likely to die or have a disabling stroke than those not treated with t-PA.

Whether these good results can be generalized to hospitals with less experience and expertise is a matter of concern, however. T-PA is a two-edged sword, with potential for both good and for harm. Patient selection and rapid treatment are the keys to its successful use. With this concern in mind, the Colorado Acute Stroke Network (CASN) was formed in January of 1996 for the purpose of monitoring the outcomes of t-PA treated patients in Colorado. CASN is sponsored by the Rocky Mountain Stroke Association, in collaboration with the National Stroke Association and the Colorado-Wyoming Chapter of the American Heart Association.

I am happy to report that, to date, the results in Colorado are at least as good as those reported in the leading national stroke centers. However, only about 1% of the stroke patients in Colorado received t-PA during the first two years that is was available. The use of t-PA is an important breakthrough in stroke treatment, but it remains underutilized. CASN is now working on ways to increase the use of t-PA for stroke patients while continuing to monitor outcomes.

Addendum (10/10/2000): CNI, in conjunction with the American Stroke Association and several other metro Denver organizations is participating in Operation Stroke, a metro-wide program to improve the utilization of acute stroke treatments.

Answer: Improving one's physical well being after stroke is not so different from improving one's physical well being in other circumstances. It involves proper diet, exercise, adequate sleep, and avoidance of harmful substances. Among the most important factors after a stroke is the rehabilitation effort. For months after a stroke, the body and brain do their best to compensate for the deficit. Physical rehabilitation can help the process along. In a sense, improvement after stroke is a matter of relearning new ways of doing old things. Practice and exercise can improve physical skills in anyone, including stroke patients. There are no short cuts, though, no pills that will take the place of hard work.

Memory improvement also requires effort. Some centers have established "cognitive rehabilitation" programs, in principle analogous to physical rehabilitation. There is controversy as to how well these work. Many doctors and insurance plans don't feel they are of proven value. Unfortunately, it seems that we know much less about rehabilitating the mind than we do about rehabilitating the body. There are no medications that are greatly helpful in improving memory following stroke. Drugs such as donepezil have shown modest improvement of cognitive performance in Alzheimer's disease, and a recent report in the Journal of the American Medical Association (1997; vol 278; p1327) suggested some benefit from Gingko Biloba in both Alzheimer's and stroke-related cognitive problems. Ask your doctor whether either of these seems appropriate for you.

Answer: Aneurysms are balloon-like dilations of arteries. They may occur in many areas of the body, including the brain. Because blood flowing though arteries is under high pressure, aneurysms are prone to rupture and cause serious, often fatal bleeding. Surgery for a brain aneurysm is a challenging undertaking. To keep the aneurysm from rupturing, various techniques are utilized, including placing a clip across the aneurysm, plugging the aneurysm with a coil, wrapping the aneurysm, or blocking off the parent artery. These procedures require great technical skill, but complications can occur--even in the most skilled of hands. Among these complications is stroke, which can result from inadvertently blocking off a small artery in the process of obliterating the aneurysm. Stroke may also occur independent of surgery as a consequence rupture of the aneurysm. Blood leaking from an aneurysm can cause a spasm of nearby blood vessels. This spasm can be severe enough to cause a stroke.

Catheters in the heart are often used to monitor aspects of the cardiac output and circulation. Occasionally, in treating very large aneurysms, surgeons elect to control the circulation with a brief period of cardiac arrest and profound hypothermia. This requires that patients be placed on cardiopulmonary bypass machines.

Answer: These questioners seek practical assistance with perceptual problems, but they ask also about a subject that is much deeper. The questions posed for this column are always challenging, but these two go beyond neurology and into the domain of cognitive neuroscience, where - I must admit - I am out of my depth. The questioners seek to know something about the mind, not just something about the brain. Each of these questions could easily be the subject of a book or a seminar.

Everyone knows that the brain is complex and incompletely understood, but let's put things in quantitative terms. The number of nerve cells (neurons) in the human brain is somewhere between 10 and 100 billion. The number of connections among the neurons (synapses) is on the order of 100 trillion. The variety of combinations in which these connections may be activated is virtually infinite.

One may think of brain function as consisting of three aspects: input systems, output systems, and between these two, processing systems. What we understand best about the brain are the input and output systems. What we understand least are the processing systems. Unfortunately for our understanding, processing systems make up considerably more than 90% of the brain. To adequately answer the current questions, we need to know a lot more about processing than we do now. We understand pretty well how sensory signals (visual, auditory, tactile, etc.) get into the brain, but what happens there to allow us to perceive and act on those signals is only beginning to unfold.

Areas of the brain that process primary sensory information communicate widely with other areas that process and manipulate the information. Out of this, perception emerges, an awareness of what it is that we sense. If the central processing is disturbed, the primary sensation may be registered correctly, but one may be unable to make anything of it. For example, lesions in the visual processing area in the rear of the brain can cause blindness, even though the eyes and the optic nerves are working perfectly. With a spatial perceptual defect, one may lose the awareness of - and the ability to attend to - certain areas of the space surrounding him. For example, a lesion of the right parietal lobe can cause one to neglect or ignore everything to his left, including the left side of his own body.

Alternatively, if the central processing areas are intact but the input from primary sensation is disrupted (a selective sensory deprivation), the central processing areas may still try to "fill in the gaps" to make some sense of signals that they are no longer receiving from the primary sensory input. In doing so, one may experience illusory images or perceptions. For example, one who becomes blind because of a problem with the eyes may still experience visual sensations or may even have well-formed visual hallucinations.

Understanding something about these curious phenomena is perhaps the first step to finding a practical way of working around them, but no general solution exists. Strategies tailored to each individual's need are required. Specialists in physical medicine and rehabilitation along with neuropsychologists are the professionals best qualified to help, but even they are hampered by the fragmentary state of our current knowledge about these conditions.

Clearly, more research is needed, and I am pleased to report that our neuropsychology colleagues at the University of Denver are actively investigating the perceptual problems of stroke survivors. For those of you who wish to learn more about this research, I urge that you contact Dr. Catherine Reed at 303-871-4622 (fax 303-871-4747).