Childhood Cancers: Brain Tumors – Signs and Symptoms, Diagnosis and Treatment

Primary brain tumors—those that start in the brain rather than spread there from other parts of the body—are the most common “solid” tumors children get and are second only to leukemia in their overall incidence. They pose a major treatment challenge that has to be met by the coordinated efforts of a variety of health care professionals, including specialists in pediatric neurosurgery, radiation therapy, and oncology, as well as neuroradiologists and neuropathologists. Significant emotional stresses and problems may occur, requiring intervention by specialized health care professionals.

Every year, about 3,100 children in the United States are diagnosed as having brain or spinal cord tumors. Many tumors are controllable or curable with treatment, and over half of the children diagnosed with brain tumors will live more than five years. Every child’s therapy should be aggressively planned with the intent to cure if possible. This is true even in situations where the same tumor occurring in an adult would not likely be cured.

As is true of all pediatric cancers, but especially with brain tumors, most advances in treatment have been produced by clinical trials of new therapies. The National Cancer Institute (NCI) oversees a large cooperative group of almost all the children’s hospitals in the country—the Children’s Oncology Group (COG)—which develops new treatment protocols for children with brain tumors. These protocols generally represent the most advanced and promising methods of treatment.

Types Brain tumors are classified by the appearance of their cells under the microscope (histopathology) and their location in the brain. The types that occur in children are generally similar to those seen in adults, although there are a few types that are much more common in children.

There is a structure in the back part of the brain, a rooflike membrane called the tentorium. This is just above the cerebellum (the portion of the brain having to do with balance and coordination) and the brain stem. There are significant differences in the types of tumors occurring above and below this membrane, as well as in the methods used to make a diagnosis and follow the results of therapy.

About half the brain tumors in children occur below the tentorium, most being in the cerebellum or the nearby cavity called the fourth ventricle. This area of the skull cavity is the posterior fossa. Tumors in this region include astrocytomas, medulloblastomas, ependymomas, and brain stem gliomas.

The area above the tentorium, which makes up most of the brain, is called the supratentorial region. Tumors in this area include astrocytomas, cerebral neuroblastomas (primitive neuroectodermal tumors [PNET]), ependymomas, craniopharyngiomas, meningiomas, germ cell tumors, optic nerve gliomas, pineal tumors, and choroid plexus tumors.

There may be many different names for these tumors, especially as newer classification systems are more descriptive or accurate.

How It Spreads Brain tumors rarely spread outside the central nervous system but can spread within the brain and the spinal cord.

What Causes It Unknown, although some genetic disorders have been associated with an increased risk.

Screening

There are no effective screening measures.

Common Signs and Symptoms

Brain tumors are often difficult to diagnose because their signs and symptoms may mimic those of other common childhood disorders. Symptoms related to the increased pressure in the brain as the tumor expands include irritability, failure to thrive, headache, nausea, vomiting (which may or may not accompany nausea), and seizures. Symptoms related to the tumor’s location and the pressure it puts on nearby structures include weakness or changes in sensation in various parts of the body, difficulties in coordination or balance, vision and speech problems, and seizures.

Diagnosis

Physical Examination

• Complete neurologic examination.

• Evaluation for optic tract glioma includes neuro-ophthalmological testing, including visual fields. Subtle changes in the tumor that may not be apparent with CT or MRI scanning can be measured in this way. Young children may have a test called visual-evoked response for diagnosis and follow-up.

Blood and Other Tests

• Bone marrow may be analyzed for tumors that spread outside the central nervous system (medulloblastomas).

• For tumors that may spread to the spinal cord or through the cerebrospinal fluid (medulloblastomas, ependymomas, intracranial germ cell tumors, pineal tumors, cerebral neuroblastomas, or primitive neuroectodermal tumors [PNET]), spinal fluid is examined for malignant cells.

• For intracranial germ cell tumors, tumor markers including alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are measured in the blood and cerebrospinal fluid. The same markers are also measured in pineal tumors to exclude the possibility of a malignant germ cell tumor.

Imaging

• Imaging has conventionally been done by CT scan for the brain and myelography for the spinal cord. Recently, MRI imaging with gadolinium enhancement has been shown to be extremely sensitive, useful, and simpler for both the brain and spinal cord.

• Images of the entire brain and spinal cord should be done for tumors that may spread to the spinal cord (medulloblastomas, ependymomas, intracranial germ cell tumors, pineal tumors, cerebral neuroblastomas, PNET).

• Bone scans and bone marrow examinations are sometimes done in medulloblastoma because this tumor may spread outside the central nervous system, especially to bone and bone marrow.

Biopsy

• Tumors of the brain stem, the medulla, and the pons (brain stem glioma) may be biopsied. The procedure is risky. They cannot be removed surgically (radiation therapy is the standard treatment). Stereotactic needle biopsy techniques may enable biopsy to be done when it could have an effect on treatment—for example, if it is not certain that a mass in this area is malignant, if the tumor grows outward and protrudes into the ventricles, or if there is a need to remove part of the tumor because of pressure symptoms.

• Biopsy of optic tract glioma is not always possible because it is difficult to expose the area surgically.

Staging

There are no generally useful staging systems for most brain tumors, although some are classified according to grade. With brain stem glioma, for example, tumors in the higher region—the midbrain—are more likely to be lower grade and have a higher chance of long-term survival than tumors lower down in the pons and the medulla (40 percent versus less than 20 percent).

A variety of staging systems have been used for medulloblastoma. The Children’s Oncology Group has divided this tumor into low and high stages groups. Essentially, low stage implies smaller tumors without metastases, in which the tumor remaining after surgery is smaller than 1.5 cubic cm. High stage refers to larger tumors with evidence of metastatic spread or brain stem involvement, and tumors larger than 1.5 cubic cm remaining after surgery.

Treatment Overview

Treatment includes surgery, with or without radiation therapy, and for some tumors, chemotherapy. Radiation therapy of pediatric brain tumors is very complex and should be carried out in facilities with extensive experience.

Chemotherapy has recently shown some activity in children with brain tumors. Children with high-stage medulloblastoma are treated with maximal surgical resection followed by radiation therapy and chemotherapy to prevent relapse. There is great interest in using chemotherapy after surgery as the only therapy in children under age three, since radiation therapy to the brain in this age group may seriously impair brain development.

Clinical Trials All children with brain tumors should be considered for entry into clinical trials. This form of cancer is rare in children, and trials offer the advantage of the pooled experience of pediatric cancer centers around the country.

Pediatric clinical trials are designed in two ways. One method divides the children into two groups, with one receiving the best currently accepted standard treatment and the other receiving the new therapy that appears promising. The other method is to evaluate a single new treatment in all patients and then compare the results with those obtained with existing therapy, often in the same institution.

Treatment by Tumor Type

Medulloblastoma

Medulloblastoma is the most common malignant brain tumor of childhood, accounting for approximately 20 percent of all primary childhood central nervous system tumors. It arises in the cerebellum and may spread to adjacent tissues. It can also spread via the cerebrospinal fluid to the rest of the brain or to the spinal cord and very rarely to sites outside the nervous system. If it occurs elsewhere in the brain, it is called primitive neuroectodermal tumor (PNET).

Standard Treatment An attempt is made to surgically remove as much tumor as possible. Studies are done during and after the operation to define the risk of relapse, and treatment is given according to the best estimate of low-stage or high-stage disease.

For low-stage disease, standard therapy after surgery is a high dose of radiation to the tumor area and a lower dose to the entire brain and spine. Lowering the dosage of radiation to reduce problems with nervous system development reduces the chance for cure. Children under three should be entered in studies that use chemotherapy and probably delayed or modified radiation therapy.

Treatment of high-stage disease involves chemotherapy in addition to surgery and radiation therapy similar to that given in low-stage disease.

These patients should be considered for entry into clinical trials to establish the best combination and sequence of chemotherapy.

Five-Year Survival About 60 percent

Recurrent Cancer Medulloblastoma that recurs after radiotherapy should be considered for treatment with investigational protocols using new agents. Fewer than one-third of those patients respond, and long-term control of disease is unusual.

Cerebellar Astrocytoma

These are generally low-grade tumors occurring in the cerebellum. Spread is unusual.

Standard Treatment The primary treatment is surgical removal of the tumor, which is successful in removing the entire tumor in most cases. In contrast to most other brain tumors, some patients with microscopic and even larger residual tumor after surgery may survive a long time without any symptoms or tumor growth even without postoperative therapy. This may be significant because a second operation may produce neurological problems.

The use of radiation therapy for patients with astrocytoma depends on the anatomic location and extent of tumor and whether it is resectable or not. Radiation therapy is indicated for unresectable tumors (midbrain and thalamic lesions).

Ten-Year Survival About 80 percent

Recurrent Cancer Cerebellar astrocytoma that recurs is treated, if possible, with another surgery. If this is not possible, local radiation is used. If it recurs in an area where it can’t be removed and has already received maximum radiation, chemotherapy should be considered. Since there is little information available about the role of chemotherapy, Phase I and Phase II clinical studies should be considered.

Infratentorial Ependymoma

These tumors arise from the cells lining the fourth ventricle (a cavity within the brain), as well as those lining a cavity in the center of the spinal cord. They can occur anywhere in the brain or spinal cord, but 60 percent of them start in the part of the brain in the back of the skull, the posterior fossa. The prognosis depends on the grade and size of the tumor and the degree of spread. These tumors may spread via the spinal fluid pathways.

Standard Treatment Surgical excision followed by high-dose radiation to the back part of the brain is the usual treatment. The tumor can be completely removed surgically in about 30 percent of cases. Radiotherapy to the entire brain and spinal cord is controversial, being used most commonly in high-grade tumors.

There is no clear benefit for adjuvant chemotherapy, although consideration should be given to using chemotherapy to delay or modify radiation therapy in very young children.

Five-Year Survival 25 to 60 percent

Recurrent Cancer This tumor is seldom controlled permanently if it recurs after surgery and radiotherapy. About one-third of patients respond to cisplatin, so Phase I and II clinical trials should be considered.

Brain Stem Glioma

Tumors arising in the brain stem are often astrocytomas, tumors of neuron-support cells. These are also referred to as brain stem gliomas. They may be low, intermediate, or high grade. The majority of these tumors growing in the brain stem cannot be removed surgically.

Standard Treatment The usual treatment is high-dose radiation therapy (over 5,500 cGy). Higher doses may be possible using twice-daily (hyperfractionated) treatment.

The role of chemotherapy is not well defined. Occasionally, patients may be candidates for surgical removal. Children younger than three may be given chemotherapy to delay or modify radiation therapy to reduce the risk of neurologic impairment.

Two-Year Survival Varies with site and grade of tumor

Investigational Chemotherapy before the standard radiotherapy treatment

Recurrent Cancer There is no standard therapy for recurrent brain stem glioma. These children cannot have surgery and have already received maximum radiation therapy, and there are no standard chemotherapy drugs that have significant results. They should be entered in a Phase I or Phase II clinical drug trial.

Cerebral Astrocytoma

 Low Grade

These tumors may sometimes be completely removed surgically, in which case they have a favorable prognosis. These tumors spread by extension to the adjacent brain and sometimes occur in multiple sites.

Standard Treatment The treatment for low-grade supratentorial astrocytoma is surgery. If the tumor cannot be completely removed, radiotherapy is given after the operation. In some centers, radiotherapy is withheld until progression of disease is shown. The role of chemotherapy is not defined, but initial results are promising.

Five-Year Survival 50 to 80 percent

Recurrent Cancer Patients may benefit from chemotherapy if tumors recur after maximum surgery and radiation therapy. No standard agents have a high degree of response, although cyclophosphamide (Cytoxan), cisplatin (Platinol), and the nitrosoureas may be useful. Carboplatin (Paraplatin) has shown promise. Consideration should be given to clinical trials.

Cerebral Astrocytoma

 High Grade

Sometimes called anaplastic astrocytoma or glioblastoma multiforme, these tumors often grow rapidly and involve portions of the brain that cause major neurological problems.

Standard Treatment Treatment includes surgery, radiation therapy, and chemotherapy. Radiation is given after as complete a surgical resection as possible to an area that encompasses the entire tumor and sometimes the whole brain.

A Children’s Cancer Group (CCG) study with radiation therapy and three chemotherapy agents (vincristine [Oncovin]+ lomustine [CeeNU] + prednisone) produced a 46 percent survival of five years compared with 18 percent for children treated with radiation therapy alone. Again, children under the age of three may receive chemotherapy to delay or modify radiotherapy. A number of clinical trials are evaluating the role of newer chemotherapeutic agents.

Two-Year Survival Less than 25 percent. The prognosis may be better if the tumor can be totally removed. Younger patients and those with lower-grade tumors may do better.

Recurrent Cancer Chemotherapy is given if relapse occurs after radiation therapy. Since no standard agents have a high degree of activity, entry in a clinical trial should be considered.

Supratentorial Ependymoma

These ependymomas arise outside the posterior fossa (back of the skull), usually within and adjacent to the ventricles.

Standard Treatment Surgery followed by radiation therapy is the usual treatment. In low-grade tumors, the primary tumor area is given radiation. With high-grade tumors, the entire brain and spinal cord are treated.

Adjuvant chemotherapy is under evaluation. Consideration should be given to its use in very young children to delay or modify radiation therapy.

Two-Year Survival About 40 percent

Investigational Various radiotherapy trials, with and without chemotherapy

Recurrent Cancer This tumor is seldom controlled if it recurs after surgery and radiation therapy, although one-third of patients respond to cisplatin. Phase I and II clinical studies should be considered.

Craniopharyngioma

These benign tumors arise in the central portion of the brain and produce problems primarily because of their location. Since they are benign, metastasis is unknown.

Standard Treatment Surgery is the treatment of choice and produces a high rate of control in most patients. For recurrent unresectable tumors, radiotherapy is recommended. There is no reported role for chemotherapy.

Ten-Year Survival About 80 percent

Intracranial Germ Cell Tumor

Germ cell brain tumors—there are a number of subtypes—usually arise in the central portion of the brain. Under the microscope, they resemble more common germ cell tumors of the testis and ovary. The prognosis relates to the cell type and is especially favorable in patients with germinoma.

Standard Treatment The role of surgery is usually a biopsy to establish the diagnosis, since the location of these tumors usually prevents complete removal. Germinoma may be treated with radiation therapy to the brain and spinal cord, with high doses to the tumor and somewhat lower doses to the rest of the nerve tissue. There is emerging evidence that local radiation therapy plus chemotherapy produces equivalent cure rates.

Advanced or disseminated germinomas, as well as the various germ cell tumors other than germinomas, are usually treated with radiation to the brain and spinal cord. There are several views about the dosage and areas that should be treated.

Nongerminoma germ cell tumors may respond to a variety of chemotherapeutic agents, including bleomycin, cisplatin, etoposide, cyclophosphamide, and vincristine. The role of adjuvant chemotherapy, in addition to radiation, is not yet determined for these tumors that arise within the brain, although chemotherapy is extremely effective in these tumors elsewhere in the body.

Survival Variable

Recurrent Cancer Intracerebral germ cell tumors may be responsive to the same type of chemotherapy combinations used against germ cell tumors in other locations—PVB (cisplatin + vinblastine + bleomycin) and VAC (vincristine + dactinomycin + cyclophosphamide).

If the tumor recurs after treatment with these programs, Phase I and II clinical studies should be used to try to find agents that may be useful in treating this tumor, which is often responsive to chemotherapy.

Pineal Region Tumors

Three principal groups of tumors—germ cell tumors, pineal parenchymal tumors, and astrocytomas—account for tumors in this region. The pineal parenchymal tumor resembles medulloblastoma, but it develops in the region of the pineal gland in the center of the brain. The prognosis depends upon the size of the tumor and its degree of spread.

Standard Treatment The usual treatment is radiation therapy. There is some controversy about the possibility of surgical removal, although biopsy is recommended whenever possible to establish a diagnosis. A high dose of radiation is given to the tumor, with a lower dose to the brain and spinal cord.

Studies are exploring the role of chemotherapy for poorly differentiated pineal tumors, although well-differentiated tumors may be treated with simple local radiation therapy. Young children may be given chemotherapy to delay or modify the radiation treatments.

Two-Year Survival Less than 50 percent

Optic Tract Glioma

These tumors grow along the optic tracts of the brain that carry visual impulses. They are low-grade and slow-growing astrocytomas that produce visual symptoms.

Standard Treatment Radiation therapy is the usual treatment for optic tract gliomas that are growing. Some tumors that do not appear to be growing and have no symptoms may be carefully observed without treatment as long as they are stable.

Chemotherapy has not been used as an adjuvant to radiation therapy as part of standard treatment, but the previous considerations about the risks of radiation in children under the age of three apply. The use of vincristine and other drugs of relatively low toxicity has enabled radiation therapy to be delayed in more than 80 percent of children and is being further evaluated.

Five-Year Survival Over 75 percent

Cerebral Neuroblastoma (Supratentorial Primitive Neuroectodermal Tumor, or PNET)

There are a variety of names for these tumors. They are poorly differentiated tumors, which microscopically may have features of various primitive tumors of other cell types. Prognosis depends upon the extent of disease.

Standard Treatment The usual treatment is high-dose radiation therapy. Many radiation oncologists also radiate the entire brain and spinal cord because of this tumor’s tendency to spread to the rest of the central nervous system through the cerebrospinal fluid. Chemotherapy has been used in several clinical trials, especially in younger children. It appears to produce good control and has particular value in younger children to delay or avoid the use of radiation therapy and its consequences. Carboplatin may be a particularly useful drug.

Two-Year Survival 30 to 50 percent

Treatment Follow-Up

• Repeated clinical evaluation, emphasizing initial neurologic signs and symptoms.

• Repeated CT or MRI scanning.

• Repeated studies of any other abnormal tests, such as cerebrospinal fluid and visual fields.

• Since radiotherapy can affect growth hormone production and brain development, careful endocrine and neurologic follow-up is very important.

The Most Important Questions You Can Ask

• What type of brain tumor does my child have?

• How does it usually behave?

• What is the chance of cure?

• What is the standard treatment and how successful is it?

• Should radiotherapy be used? When?

• Should chemotherapy be used? When?

• If the treatment is not completely effective or my child relapses later, what else can be done?

Pharmacology and Herbal Supplements for Brain Improvement

The United States Pure Food and Drug Act became law on June 30, 1906. This legislation mandated the federal inspection of meats and banned the sale of adulterated food products and poisonous drugs. In 1938 the Federal Food, Drug, and Cosmetic Act established the United States Food and Drug Administration (FDA). This agency was given the responsibility for ensuring the safety of food, pharmaceuticals, and cosmetics and, subsequently, was empowered to assess and verify drug efficacy. Given these and other legislative mandates, a drug candidate must now undergo years of rigorous laboratory animal and human testing before the manufacturer gains FDA approval for sale to the general public.

Hundreds of millions of dollars are needed to cover the costs associated with meeting FDA criteria for a single, new drug product. Among these requirements is detailed information on its chemical and pharmacological properties. Convincing evidence must be submitted that the compound is safe and efficacious at the recommended dose. Side effects and toxicities must be identified, including information on potential interactions with other drugs that may be taken by the patient. The intended use must be defined precisely on the basis of clinical research results. Data are required on the purity and stability of the manufactured product. After a drug is approved, federal inspectors routinely monitor its production and use to ensure product consistency and appropriate marketing.

Given these safeguards, it is not necessary for consumers to be concerned about the safety and effectiveness of prescription or over-the-counter medications. While not all drugs are effective in all patients, and there can be idiosyncratic responses, consumers can reasonably assume that if an FDA approved product is taken as directed it will likely display some efficacy as a treatment for their condition and that they will be alerted to potential side effects. Accurate information on the limitations of use and possible toxic reactions is usually obtained from the health care provider and is readily available in the manufacturer’s description of the product and in other forums.

The situation is different for herbal supplements. Given their growing popularity in the 1980s, Congress needed to decide whether these products should be subject to federal regulations covering foods or drugs. In the United States this resulted in the Dietary Supplement Health and Education Act of 1994. As this legislation defined these products as food supplements, producers are not required to provide proof of safety or any health benefit before offering them for sale. While a statement regarding safety must be submitted to federal authorities, the burden of proof is on the government to raise questions about possible dangers associated with use. If the government registers no objection within a specified period, the product may be sold. Given the lack of regulation and oversight, those selling such products are forbidden to refer to them as drugs and to advertise any therapeutic benefit. To comply with this requirement, product labels often contain a disclaimer indicating it is not to be used to diagnose, treat, cure, or prevent any disease. As a practical matter, however, broad, misleading claims about the therapeutic benefits of dietary supplements are commonly encountered, especially on the Web.

The number and popularity of these products has continued to expand, with more than $5 billion in sales in the United States in 2009. Because of growing concerns about product contaminations and the quality of the ingredients used to manufacture some supplements, new regulations were enacted in 2003 to allow government inspectors access to company manufacturing records to monitor quality control. However, it cannot be assumed that all herbal product manufacturers routinely undergo such inspection given the number of companies, the fact that many are located abroad, and the shortage of FDA personnel. The absence of federal requirements regarding safety and efficacy, and the minimal manufacturing oversight, leaves the consumer responsible for assessing the potential risks and benefits of these products. Besides a paucity of objective research data, this determination is complicated by the fact that neither the potential user nor the manufacturer can always be sure of the number and type of biologically active constituents in these extracts. This makes it difficult to assess what effect the supplement may have on otherwise healthy individuals, let alone those with a chronic or acute illness, those taking prescription medications, or who are undergoing other kinds of treatments, such as radiation therapy.

When developing new drugs, safety and efficacy issues are addressed by basic and clinical pharmacologists. To this end, pharmacologists consider a number key principles. While this task is simplified when examining a single, purified substance, these same principles can be applied, although to a more limited extent, to plant extracts when deciding whether a product might be of benefit. The information contained in this post is intended to provide a broad overview of these basic pharmacologic principles and to define terms and concepts useful in making an informed judgment about the potential utility of an herbal product. The aim is to help the consumer think like a pharmacologist when considering the possible use of a dietary supplement. Although the quality and quantity of the publicly available research data are limited for these products, an understanding of these principles and terms will enable the consumer to make a more informed decision about the potential value of a particular product.

 

The Brain as a Drug Target – Herbal Supplements

Transmitters are chemicals synthesized in neurons. Two dozen or so chemical substances have been identified as brain neurotransmitters. These agents are the primary means of communication between brain cells. Transmitter vocabulary is limited, however, in that a given agent either enhances or decreases the firing of an adjacent neuron. By affecting the excitability of the neuron, transmitters influence the way the receptive cell modifies the activity of neighboring neurons. In most cases the transmitter is stored in packets, called vesicles, in the nerve terminal (refer to Figure 4.1). When the neuron is stimulated an impulse travels along the axon causing the vesicles to fuse with the presynaptic axon terminal membrane, to open, and then to discharge the stored transmitter into the synapse (refer to Figure 4.1). Once released, the transmitter diffuses across the synaptic cleft and attaches to its receptors on the adjacent postsynaptic neuron. Typically, the postsynaptic membrane is located on the dendrites of an adjacent cell. Attachment of the transmitter to its receptor enhances, in the case of excitatory neurotransmitters, or inhibits, in the case of inhibitory neurotransmitters, the activity of the postsynaptic neuron. If the neuron is stimulated, the impulse generated facilitates the release of the neurotransmitter from its axon terminals to transmit a signal, which is either excitatory or inhibitory, to adjacent neurons. By slowing the firing of the receptive neuron, inhibitory transmitters decrease transmitter release from the adjacent cell which, in turn, influences the firing of neighboring neurons. Thus, overall brain activity represents a delicate balance between excitatory and inhibitory transmitters.

Besides being localized on postsynaptic membranes, neurotransmitter receptors may be found on presynaptic terminals. When activated these presynaptic receptors slow the release of a transmitter from that terminal by causing intracellular biochemical changes that reduce vesicular attachment to the membrane. Thus, if an excessive amount of neurotransmitter is being liberated from a presynaptic nerve terminal, some will leak out of the synapse and stimulate the presynaptic receptors, slowing further transmitter release in an attempt to return the system to equilibrium. It is also possible that an axon from a neighboring neuron may synapse with a presynaptic, rather than postsynaptic, membrane. This is referred to as an axo-axonic, as opposed to axo-dendritic, synapse. If there is an axo-axonic interaction the rate of transmitter release from a terminal is regulated not only by the firing rate of that neuron, but also by the activity of an adjacent cell releasing its transmitter onto the presynaptic receptors.

Once a neurotransmitter activates its receptor it is released back into the synapse. Some transmitters are destroyed by metabolizing enzymes located at or near the synapse. Many are also transported back (reuptake) into the presynaptic terminal where they may be metabolized intracellularly or re-stored in vesicles for future use.

The elements involved in synaptic transmission provide many targets for manipulating this process pharmacologically. For example, brain neurotransmitter function can be modified by agents that inhibit the synthesis, metabolism, or storage of neurotransmitters, or their reuptake into the presynaptic terminal. Agents are also known that enhance the release of certain neurotransmitters. Commonly drugs, and possibly natural products, directly interact with neurotransmitter receptors, either activating (agonists) or blocking (antagonists) these sites. Brain neurotransmission is also affected by drugs that interact with neuronal ion channels or ion transporters. The passage of ions across the neuronal membrane is essential for transmitting nerve impulses and for maintaining a healthy intracellular environment. Activation of some receptors can affect ion channel activity or ion transport, thereby modifying cellular excitability and stability. Likewise, chemical agents can modify brain function by attaching directly to these sites.

There are many other potential drug targets in neuronal tissue besides those involved directly with chemical neurotransmission. Included are enzymes, such as kinases and phosphatases, responsible for modifying protein function, and intracellular receptor systems, such as those for certain hormones, which regulate gene expression in the cell nucleus.

The Gifts of Eden – Herbal Supplements for Brain

Adam wasn’t hungry and was apprehensive about the potential consequences of eating the forbidden fruit. He was, however, convinced the plant material could provide benefits beyond its nutritional value. On the one hand, God told him that its consumption would be fatal, while the serpent contended the plant would impart new knowledge. Both were right. After eating the fruit Adam lost his home and immortality, and was made aware of the concepts of good and evil. He would need this new knowledge to survive in the world outside of Eden.

Besides its allegorical importance for Jews, Christians, and Muslims, this biblical account provides lessons for those interested in the therapeutic benefits of herbal supplements, also known as nutritional, dietary, or food supplements. Defined as a product that contains a vitamin, mineral, herb or other botanical, an amino acid, an extract, or any combination of these materials, the United States government considers dietary supplements to be foods rather than drugs. This has significant implications with regard to their regulation and the assurances provided to consumers. Because of this categorization, potential users must obtain on their own objective data about these products. The aim of this website is to provide such information.

The most fundamental question pertaining to dietary supplements is whether there is any evidence that they provide benefits beyond possible nutritional value. Written some 2,500 years ago, the Genesis account of Adam’s introduction to these products indicates that humans have been familiar with the possible mystical and therapeutic powers of plants for quite some time. Moreover, the Old Testament account demonstrates that then, as now, there was uncertainty, and therefore risk, associated with the consumption of plants and plant products for religious, therapeutic, or, as in Adam’s case, educational purposes.

The fruit consumed by Adam is unknown. In Old English, the word “apple” is simply a synonym for fruit. Regardless, when tempted to eat the plant product, Adam was at a distinct disadvantage to today’s consumer. There was no historical record on its possible effects and no scientific data on its safety. Moreover, as the basic principles of pharmacology, the science of drugs, had not yet been established, he was unable to assess these properties himself. Rather, Adam had to rely solely on the word of others.

The constraints experienced by Adam remained for thousands of years until written records were maintained on the medicinal value of plants. More centuries passed before chemists were able to identify, and pharmacologists objectively study, the therapeutically active constituents in plant and animal products. Only during the past century has research revealed the diseases and disorders that are most responsive to these constituents, and to define precisely the appropriate doses to maximize safety and effectiveness in most individuals.

Anecdotal accounts about the potential benefits of dietary supplements have existed for thousands of years. Evidence includes pollen grains found on Neanderthal (Homo neanderthalensis) graves that were from plants lacking showy flowers, such as the yarrow (Achillea millefolium). It is inferred that these plants were placed there not for adornment, but to provide the departed a supply of medications in the afterlife.1 This concept is based, in part, on the fact that many of the plants deposited on Neanderthal gravesites were subsequently described as therapeutics in early medical books, indicating that word of their therapeutic powers was passed on for millennia. For example, yarrow is mentioned in the Assyrian Herbal (800 BC), one of the oldest listings of therapeutically active plant products,2 as well as in the Ebers papyrus (1500 BC) from Egypt. The Greek poet Homer described in The Iliad (800 BC) the use of yarrow to cure wounds, as did the Roman naturalist Pliny the Elder in his writings during the first century AD.3

A conservative estimate is that plants have been used as therapeutics at least since the appearance of modern man, some 200,000 years ago. It seems reasonable that as early humans foraged for food they would accidently discover the curative powers of some plants or take note of the fact that consumption of a certain type of seed, root, or fruit produced discernable effects on mood, sensory input, or alleviated general aches and pains. Indeed, as a species, humans are indebted to the many thousands of forgotten ancestors who became ill or died in the process of identifying plants and animals suitable for consumption. Thus, through trial and error, early man was able to identify plants that possess useful medicinal properties.

In addition to using plants to cure disease, they were also consumed in the ongoing quest for immortality. Recipes for “elixirs of life” were described in ancient writings. An example is the Epic of Gilgamesh, the story of a Sumarian hero that was recorded in 2000 BC.4 After many travails, Gilgamesh obtained the plant of immortality from deep in the sea. Unfortunately for Gilgamesh, the plant was subsequently stolen by a serpent. This tale has many of the features of the biblical account of Adam and Eve. In the end, Gilgamesh returned home to Sumer to, like the rest of us, spend the remainder of his days as a mortal, awaiting the inevitable.

As in Genesis, ancient medical texts demonstrate that plant products have been used for therapeutic purposes for millennia. During most of this time no concerted effort was made to understand the reason for their effectiveness, or, in modern terminology, their mechanism of action. The first recorded attempts to synthesize therapeutics were made by European alchemists during the Middle Ages.5 Besides their efforts to transform base metals into gold, the alchemists were interested in what made substances therapeutically useful as they wanted the power to transform basic materials into drugs. They were hindered in this quest, however, by the prevailing theories about the nature of matter and the causes of disease.

From the time of Aristotle to the seventeenth century, the use of plants in European medicine was based on the idea that all nature was composed of four basic elements: earth, air, fire, and water. Disease resulted from an imbalance of bodily humors. It was believed this imbalance could be countered by one or more of the four plant classes—cold, dry, hot, and wet—that corresponded to the four basic elements of nature. Mixtures of plants, usually from the same class, were preferred over a single specimen for treating medical conditions. For example, combinations of “cold” plants were used to treat fevers. Given these theories, drug discovery remained an empirical enterprise for thousands of years, with the identification of active plants and plant products left solely to chance.

 

By the seventeenth century, belief in the Aristotelian four elements was being challenged, most notably by the Irish chemist Robert Boyle.6 Boyle understood that the precise identification and classification of the basic elements of nature were absolutely essential for understanding the universe, including drug actions. Thanks to his efforts, and those of many others, modern chemistry emerged in the nineteenth century. This made it possible to isolate, chemically define, and study the biological responses to plant constituents. As a result of these efforts, drugs were identified in plants that were first discovered by our distant ancestors. Many of these compounds, or their chemical derivatives, are still used today.

Given the historical records, and contemporary scientific data, there is no question that plants produce an abundance of substances that provide benefits beyond their nutritional value. However, not all plant constituents have been isolated and properly tested for effectiveness, and, unlike drugs, there is no government requirement that a manufacturer demonstrate effectiveness before marketing an herbal supplement. Like Adam, the consumer must rely on the word of others about the benefits of these products.

This website is designed to address this issue by providing basic information needed to assess the potential therapeutic value of plant products. Included are fundamental principles of pharmacology and about how drugs and natural products can affect various organs and organ systems. Explanations and examples are provided about what determines whether an ingested substance will find its way into the bloodstream, and then to the targeted site in the body at a concentration sufficient to have a beneficial effect. Other topics include the ways in which natural products may influence the blood levels of other substances, including drugs, and the likelihood that such interactions may diminish the effectiveness of prescription medications or alter normal body chemistry.

While the principles described apply to all dietary supplements and drugs, emphasis is placed on factors that relate especially to herbal supplements purported to influence brain function. Individual posts are devoted to a discussion of selected nutritional supplements that are said to enhance memory, or to aid in the treatment of depression, anxiety, insomnia, and alcoholism. These products were chosen because the promised benefits can be difficult to quantify and are more subject to influence by the power of persuasion than is the case with other therapeutics. This is why the use of such substances has been exploited over the centuries by shamans to maintain their social standing, and by charlatans for monetary gain.

The properties of these products are described in the context of the basic principles of pharmacology and the results of scientific studies, both human and laboratory animal, aimed at determining effectiveness and mechanism of action. The approach taken in objectively evaluating these products can be used by the reader as a guide for assessing the information available on any dietary supplement. This work is intended for those who are curious about the potential benefits and risks associated with the use of food supplements. The information provided will be of particular value for individuals who, like Adam, are interested in how drugs and natural products affect us for good and evil.

Herbal Supplements for Brain -Transforming Plants into Gold

Other prehistoric evidence suggesting the use of plants for medicinal purposes includes the discovery of valerian root in caves inhabited 35,000 years ago by Cro-Magnon.8 As the valerian root grows horizontally along the surface of the ground, it would be easily noticed and harvested for its nutrient and medicinal value.

Life Care Planning for Acquired Brain Injury – Case study and Conclusion (III)

A 32-year-old client was riding a motorcycle that was hit by a car. At the time of the interview, 3 years postinjury, he stated that he did not remember the incident or anything a couple of weeks prior to the incident. Following the incident, his first consistent memory is approximately 2 to 3  months later. He was treated for 2 months in an acute care hospital and then for 5 months in a brain injury rehabilitation hospital. The client was diagnosed with severe TBI with physical and cognitive deficits, including ventriculoperitoneal shunt and orthopedic injuries requiring extensive care.

Neuropsychological testing results concluded that the client had sustained a very severe TBI. Testing revealed reduced intellectual capacity of one standard deviation, perhaps slightly more, below preinjury levels. His primary deficit is in visual/motor problem solving. He is able to sight read beyond a high school level. He has significant deficits in mathematical calculations, with overall performance at a level much lower than expected given his preinjury educational level. No anomia was noted, and he is able to mildly retrieve words without perseveration or intrusive errors. He has significant difficulty with fine motor coordination, with reduced range in the left upper extremity. He has significantly improved executive function from prior testing, which is the most promising part of the overall evaluation, although he continues to exhibit occasions of temper outbursts. He has moderately to severely impaired short-term memory, especially with verbal short-term memory given the absence of consolidation of information. He has a positive affect, although he has times of unhappiness/frustration, and is basically functioning in a more adaptive manner.

He has a young daughter and must be supervised when with her. His wife is supportive and has quit work to be his caregiver. He must have someone available for assistance with judgment, safety, food preparation, and financial commitments. Work is not a reasonable goal, although volunteer activities part-time would be therapeutic.

LIFE CARE PLAN

Note: For purposes of this plan, the following initials are placed in parentheses according to their respective recommendations:

JP   = Jeffrey Preston, MD, physiatrist

MC = Michael Cathy, MD, psychiatrist

RH  = Robert Hampton, MD, ophthalmologist

IR   = Ian Raston, MD, hand surgeon

WW = William White, MD, internist

AP  = Amy Passy, PT, physical therapist

JH   = John Hurry, PsyD, neuropsychologist

RW = Roger Weed, PhD, life care planner

Routine Future Medical Care—Physician Only

Physiatrist (JP)

X-rays: left hip, knee, or shoulder (JP)

Head CT scan (JP) Head MRI (JP)

EEC (JP)

4  times/year to life expectancy 3 times/year to life expectancy 1 time/year to life expectancy Every 5 years to life 1 time/year to life expectancy

Monitor overall rehabilitation program and prevent/reduce complications, etc. Monitor development of expected degenerative joint disease Assess integrity of shunt Monitor structural changes to brain Assess brain wave activity due to high risk for seizures

$276-320/year at $69-$80/ visit (see Note 1)

Range: $609-1365/year at $203-455 each, 3 times/ year to life

CT scan: $2173-2296/year to life

MRI: $3016-4370 every

5 years to life

EEC: $854/year to life

Note 1: Dr. Preston states in his deposition that a personal computer is medically indicated for the client to include possible access for environmental control unit (ECU) or adaptive devices integration in the future.

Note 2: A one-time-only replacement cost for computer and related equipment/supplies is included in plan. Replacement after that is presumed to be consistent with use of a personal computer by the general population.

Note: The client has no competitive vocational potential. Volunteer activity is a best option for him to increase his sense of productivity and self-worth, and provide a sense of purpose. If professional services are required in the future to develop or cultivate an alternate volunteer program for the client, expect 20 to 40 hours for vocational counseling and related services, including vocational evaluation, labor market research, job site analysis, etc., at $75 to $89/hour. However, costs for these services are not included in the plan.

Architectural Considerations

(List considerations for home accessibility and modifications.)

The client currently lives with his wife and 2-year-old daughter in a ranch-style house that has been modified to accommodate him and generally appears appropriate for his current needs. A ramp has been constructed to the back door, which is the entrance the client uses to enter and exit the home, and grab bars have been installed in the bathroom. The front entrance has steps leading to the front door, although no handrail is available and the client demonstrates he generally is able to ascend and descend the stairs with difficulty in a modified fashion and with altered gait.

The client requires a one-story home with accessibility features and minimal, if any, stairs. If stairs, he requires handrails. See also home accessibility evaluation for one-time-only evaluation to assure the home is accessible both now and for the future as he ages and experiences an expected reduction in his physical capabilities.

Left total knee replacement (JP)

Left knee revision (JP) 2020 (age 50) Approximately 2030-2032 and every 10-12 years (average) thereafter to life expectancy

Initial knee replacement in 2020, then every 10-12 years (average) knee revision to life expectancy

Replacement in approximately 2020: $30,948

1st revision: $35,608 2nd revision: $34,378

Left total hip replacement (JP)

Left hip revision (JP) 2020 (age 50) Approximately 2030-2032 and every 10-12 years (average) thereafter to life expectancy

Initial hip replacement in 2020, then every 10-12 years (average) hip revision to life expectancy

Replacement in approximately 2020: $31,568

1st revision: $39,811 2nd revision: $37,479

*Expected cost for knee and hip replacement/revision includes surgeon fee and average hospital charges and does not include surgeon assistant fee, if applicable, anesthesiologist fee, or sub­acute or rehab unit stay. One case of a client similar in age to this client with diagnosis of degen­erative joint disease required total knee replacement at a cost of $40,733, inclusive.

Note 1: The physiatrist states he expects the client to require joint replacement in both left hip and left knee due to altered gait and increased wear and tear on his lower-extremity joints as well as expected degenerative joint disease. He states the severity of the degenerative joint disease depends on maintenance of the client’s weight and overall health and fitness.

Note 2: According to one orthopedic surgeon who performs knee and hip replacement surger­ies, knee and hip prostheses last on average 10 to 12 years (based on geriatric popula­tion); however, the client may require more frequent revision due to his young age at time of projected initial replacement and expected increased activity level (more so than geriatric activity level). See also Potential Complications.

Note 3: For purposes of future care planning and based on the physiatrist’s recommendation for initial hip and knee joint replacement at approximately age 50, presume two hip and knee revisions over the client’s lifetime at approximately age 60 to 62 and age 72 to 74.

Note 4: The orthopedic surgeon states joint revision surgeries are more difficult than the initial replacement surgery and each subsequent revision is more difficult than the previous one. Recovery also tends to take longer. However, no additional cost for extended recovery is included in plan totals for revision surgeries.

Note 5: Pain medication is expected to be needed following each joint revision surgery as well as probable anti-inflammatory medication. Exact kind, dose, and duration of medica­tion are unknown and no additional cost for medications is included in plan totals.

Note 6: Orthopedic visits following joint replacement/revision generally include one post-op visit (at no cost) plus three other visits at 3, 6, and 12 months postreplacement/postrevi­sion at $60 to $80/visit. Routine follow-up also includes AP and lateral x-rays of hip at $174.25/x-ray and knee at $261.25/x-ray at each post-op visit. Additional medical needs following joint replacement/revision likely include postoperative physical therapy and

probable long-term need for cane or walker for mobility assistance. Aqua therapy also may be indicated following joint replacement/revision.

Ventriculoperitoneal (VP) shunt revision (JP)

Approximately 2011 (15 years after initial shunt placement)

1  time only, assuming no complications

Neurosurgeon evaluation: $286 Revision surgery: $28,927

Note 1: The client was released from the care of his neurosurgeon in February 1998 to be fol­lowed by the physiatrist and return as needed if there were complications with his shunt or changes in his neurologic status. The physiatrist states it is probable the client will require at least one shunt revision over his lifetime due to expected complications.

Note 2: Expected cost for VP shunt revision includes surgeon fee and hospital charges only and does not include diagnostic studies that may be needed such as abdominal x-rays or head CT scan, or anesthesiology charges. See head CT scan, which may be used for diagnostic purposes at time of shunt revision.

Note: Potential complications are included for information only. No frequency or duration of complications is available. No costs are included in the plan.

Life Care Planning for Acquired Brain Injury – Classification and Complications (II)

Life Care Planning for Acquired Brain Injury – Anatomy of the Brain (I)

Life Care Planning for Acquired Brain Injury – Case study and Conclusion (III)

Brain injuries can be classified by a number of methods (Marshall et al., 1992; Teasdale et al., 1992). ABIs are generally classified as traumatic, anoxic/hypoxic-ischemic, vascular, or other.

Anoxic or hypoxic-ischemic brain injuries occur when areas of the brain do not receive enough oxygen. This is frequently the cause of secondary injury after a traumatic injury, but may also occur independently of trauma. The most frequent cause of hypoxic-ischemic brain injury is sec­ondary to myocardial infarction or heart failure. During resuscitative efforts for a heart attack, the brain may be deprived of oxygen for several minutes. Vascular brain injuries, commonly called strokes, most commonly occur as a result of thromboembolic phenomena. However, other types of vascular brain injuries include aneurysms, arteriovenous malformation, and spontaneous intracra­nial hemorrhages. Finally, injury to the brain may occur as a result of viral or bacterial infections, metabolic derangements, or tumors.

Traumatic brain injuries, the broadest category of ABI, may be further subdivided a number of ways. One of the most basic methods of subcategorization is to divide them between open or closed. Open injuries are those injuries in which there is disruption of the scalp and skull, creating the possibility that the brain may be contaminated by material from the outside environment. Penetrating brain injuries are a type of open injury, in which a foreign body (such as a bullet) passes through the skull and outer coverings of the brain into the brain tissue itself. Closed head injuries are those in which the skull remains intact and the brain is not exposed to the outside environment, although significant injury may occur from the impact of the brain against the inner part of the skull, or from shearing of axons secondary to rotational forces.

Medical professionals caring for survivors of brain injury will also classify the injuries based on severity. The most common, widely utilized method of classification is the Glasgow Coma Scale, a method that classifies injuries based on clinical presentation (see Table 13.1). A medical professional will rate the patient’s response in three separate areas: eye opening, motor response, and verbal response. The scale gives scores for each of the areas, which are summed to give a total score that can be used to rank the severity of the injury. Individuals who score 3 to 8 are said to have a severe injury, from 9 to 12 a moderate injury, and from 13 to 15 a mild injury. This information may be useful to predict the outcome and likelihood of long-term impairments (Clifton et al., 1993; Zafonte et al., 1996; Teasdale et al., 1998).

Other methods of rating injury severity are available but not as widely utilized. One alternative method of injury classification uses duration of posttraumatic amnesia as the best method of pre­dicting outcomes following TBI (Zafonte et al., 1997). Other methods of classification have tried to use radiographic findings, such as location and size of lesions on computed tomography (CT) or magnetic resonance imaging (MRI) (Teasdale et al., 1992). However, the correlation between radiographic findings and clinical presentation is often poor. Newer MRI techniques are now available in some areas, which have greater sensitivity to injured brain tissue and greater clinical correlation with functional status (Gerber, Weintraub, Cusick, Ricci, & Whiteneck, 2004).

Another broad categorization of brain injury is to divide between diffuse and focal brain inju­ries. Diffuse injuries are generally due to shearing injury of the axons and generally occur across a broad area of the brain. Focal injuries occur with trauma to one specific region of the brain. These two types of injury may occur concomitantly. In general, focal injuries result in shorter periods of unconsciousness than diffuse injuries. Individuals with diffuse injury, sometimes referred to as diffuse axonal injury (DAI), may have prolonged periods of unconsciousness from several days to weeks. In general, individuals with DAI have a prolonged recovery period compared to those with focal injuries (Bontke & Boake, 1991; Berker, 1996).

When a patient presents to the emergency room following TBI, the initial activities focus on life preservation. Often, concomitant injuries preclude addressing the brain injuries until later in the course of treatment. However, for those patients with severe injuries, the initial protocols involve rating the patient’s level of arousal using the Glasgow Coma Scale, and some form of neuroradio­graphic imaging. At this time, CT scan remains the preferred type of image, due to the relatively faster speed with which images can be obtained and the fact that the types of injury that require emergency surgical intervention show much more readily on CT than MRI. However, there is some discussion about whether newer MRI techniques are more sensitive to intracranial injury (Levin, 1992; Marshall et al., 1992; Rappaport et al., 1992; Piek, 1995; Horn & Zasler, 1996; Gerber, Weintraub, Cusick, Ricci, & Whiteneck, 2004).

Incomprehensible verbal utterances(Sum of score from each of three areas)

Note: A score with a T (e.g., 8T) means the patient was intubated for airway purposes and may be unable to fully respond.

Once the patient is stabilized, a more detailed assessment of the injury will occur, and further treatment may be recommended. For severe injuries, assessment by a neurosurgeon will usually occur. If there is evidence of specific, severe types of bleeding or increased pressure inside the head, surgery will be performed to evacuate the blood or alleviate the pressure. Sometimes an intracra­nial pressure monitor will be placed to accurately measure the pressure inside the brain.

Patients frequently require assistance with basic life functions. They may be placed on a mechanical ventilator to help them breathe. For prolonged management, sometimes a trache­otomy is performed to facilitate prolonged ventilator support. Additionally, for patients that are unconscious for prolonged periods of time, a feeding tube may be surgically introduced. Many patients with severe injury will also sustain injuries to other parts of their body as well. Surgical attention is often necessary during the early hospitalization to address fractures, damaged internal organs, internal bleeding, and other medical concerns.

While patients are still in the hospital, physical and occupational therapy referrals should occur to maintain joint range of motion and strength and to begin working on activities of self-care. The more severely injured patients should be referred to a rehabilitation facility following their acute hospitalization to begin the work of trying to be restored to their highest level of functioning. An assessment by a physiatrist, a medical doctor with training in physical medicine and rehabilitation (PM&R), is important during this phase to facilitate the coordination of services and medical treatment to promote the best outcome following TBI (Rosenthal, 1990; Almli & Finger, 1992; Bontke et al., 1993; Berker, 1996; Semlyen et al., 1998).

Patients will often require further medical and rehabilitation care after medical issues are stabilized (Cope, 1995). Several different levels of rehabilitation care are possible, and the best appropriate level of care depends on the acuity of the concomitant medical issues as well as the level of functioning of the patient (Evans, 1992; Mazmanian et al., 1993; Hall & Cope, 1995; Schmidt, 1997). Patients who cannot participate or tolerate several hours of therapy each day are most appropriately sent to a subacute rehabilitation program until they can tolerate a more aggressive therapy program. The most common level of rehabilitation care is acute inpatient reha­bilitation, where patients receive 3 or more hours of therapy a day from several different therapy disciplines (i.e., physical therapy, occupational therapy, speech therapy), as well as ongoing medical attention (Malec & Basford, 1996). Once patients are medically stable and safe to be managed at home, therapy efforts transition to an outpatient setting. Rehabilitation day programs are therapy programs designed for individuals who still need therapy from several different disciplines in a team format, but no longer need as close medical attention as individuals in the acute inpatient setting. Some individuals will not need the interdisciplinary model of therapy, but only require therapy from one or two disciplines; then single-service outpatient therapy is indicated.

An adept life care planner who works with survivors of brain injury must be aware of the potential medical complications that arise following brain injury and their impact on recovery, long-term function, and reintegration in the community. As the brain is the control center for all neurological processes in the body, injury to the brain can result in complications to almost every organ system. It is beyond the scope of this post to discuss all complications, although there are several common complications that we will describe (Kraus, 1984, 1991; Corrigan & Mysiw, 1988; Bigler, 1989; Bloomfield, 1989; Russell-Jones & Shorvon, 1989; Uomoto & Brockway, 1992; Bontke et al., 1993; Jore et al., 1993; Katz & Alexander, 1994; Kaufman et al., 1994; Piek, 1995; Cifu et al., 1996a).

Injury to the cranial nerves frequently occurs following TBI. As a result, patients may have dif­ficulty with basic sensory functions, such as vision, hearing, smell, and taste. Facial paresis is fre­quently seen, with resultant difficulty in oromotor functions, as in speaking, resultant dizziness, and balance disorders. This by itself may lead to problems with standing, walking, and transfers. It is very common for the olfactory nerve, the cranial nerve that controls sense of smell, to be dam­aged due to its structure, sometimes resulting in problems with eating and appetite. Fractures of the temporal bone, a part of the skull, can result in disruption of the cranial nerve associated with hearing, resulting in hearing impairment.

Many patients will have significant difficulty with vision problems following brain injury. Problems may range from inability to see objects in certain parts of the field of vision (sometimes referred to as a field cut) to blurry or double vision. This may be due to injury to the visual pathways within the brain, to injury to the nerves that control eye movements, or to injury to the eye itself. An evaluation by a neuro-ophthalmologist, a physician with training in neurological disorders that affect vision, is sometimes very helpful.

Endocrinology is the study of hormones and their function. Many hormones are regulated or secreted by the pituitary gland, a structure at the base of the brain. The pituitary can frequently be damaged during injury to the brain due to its location and structure. Common endocrine disorders following brain injury include syndrome of inappropriate diuretic hormone (SIADH), growth hormone deficiency, and irregularities of gonadal steroid production. Endocrinopathies are much more evident in women, because menstrual irregularities, as a result of altered pituitary- gonadal axis functioning, may persist for a year or longer after brain injury. This may also be a source of problems with infertility following injury.

Patients with severe TBI frequently have respiratory failure as sequelae of the initial trauma. As a result, patients often require mechanical ventilation with a breathing machine (ventilator). Sometimes physicians must perform a tracheotomy, or a surgically created hole, to allow the patient to breathe and to help prevent complications from prolonged ventilator management. Patients who are immobile for prolonged periods of time are at a higher risk for developing pneumonia. A pulmonary embolus, or a blood clot that lodges in the blood vessels of the lungs, is also a potential complication of prolonged immobility.

Direct effects of brain injury on the cardiovascular system are infrequent. However, immobility may lead to secondary complications over time. The most common is the formation of deep vein thromboses (DVTs) or blood clots in the veins. These clots can be potentially life threatening, as they can break free and lodge in the lung vessels causing a pulmonary embolus, as noted previously. DVTs may also result in postphlebitic syndrome, or a painful condition of inflammation of the veins. Another complication that may lead to cardiovascular injury is called central storming, in which abnormally high levels of stimulant hormones are released into the bloodstream, resulting in fevers, high heart rates, and high blood pressure. This phenomenon can result in heart injury to people who are susceptible.

Typical neurological problems include weakness, sensory deficits, and the previously mentioned cranial nerve problems. Individuals who have had a brain injury are at increased risk for develop­ing seizures. The presence of a penetrating brain injury, skull fracture, or significant amounts of subarachnoid blood increases the risk for seizures. The upper motor neuron syndrome is possibly the most frequently seen neurological complication after all forms of brain injury, with its constel­lation of symptoms of weakness, spasticity, and increased reflexes. Spasticity is a velocity-dependent increase in motor tone that is seen frequently following injury to motor nerves in the central ner­vous system. This is such a profound problem after brain injury that it will be discussed in detail later in the post. Additionally, cognitive and behavioral problems are frequent neurological com­plications and will also be discussed in more detail later.

Patients frequently exhibit dysphagia, or impairment in the ability to swallow, as a result of weak­ness of the pharyngeal muscles. Often, patients require the placement of a feeding tube to prevent aspiration of food and to allow for feeding while the pharyngeal muscles remain weak. Additional gastrointestinal problems may include incontinence secondary to neurological impairment of the muscles controlling bowel function or alternatively from cognitive impairment. Constipation is frequently seen due to the same alteration in neurological functioning of the bladder, or often due to medications.

Neurological control of the bladder may be impaired, resulting in incontinence. However, most cases of incontinence following brain injury are a result of disinhibition instead of true neurological impairment. Patients with neurological impairment of bladder function may retain urine, which can lead to other problems, including frequent infections of the urinary tract, infection of the kid­neys, and renal and bladder stones. Sexual dysfunction may also be an issue, although, again, these problems are predominately behavioral as opposed to physiological impairment of sexual function­ing. Frequently, sexual inhibition may occur as a result of altered body image due to impairments such as weakness, spasticity, or changes in physical appearance due to the injury, although more frequently, patients become sexually disinhibited due to injury to the areas of the brain respon­sible for control of impulsive behavior (Kreuter et al., 1998). Sexual functioning is an area that is
frequently overlooked by medical professionals. In women, infertility may occur secondary to the endocrine changes mentioned earlier.

Musculoskeletal complications are very common following brain injury. Injury to the motor nerves in the brain may result in the upper motor neuron syndrome, which consists of the constellation of symptoms of spasticity, weakness, and hyperreflexia. Areas of weakness can vary depending on where the injury is located in the brain. Due to the brain’s structural organization, injury on one side of the brain results in weakness on the opposite side of the body. Additionally, the weak side is frequently associated with spasticity. If unchecked, spasticity and immobility may ultimately result in contractures, which is tightening of the soft tissues and shortening of tendons around a joint resulting in a reduction in the patient’s mobility. As a result of associated trauma, patients with brain injuries also frequently have associated fractures, peripheral nerve injuries, or soft tis­sue injury that can also make rehabilitation difficult. An interesting musculoskeletal problem that sometimes occurs following TBI is heterotopic ossification, a condition in which bone is formed inappropriately in soft tissue areas. This problem, if left untreated, can result in ankylosis, or fusion of a joint, such that moving it is impossible. Extremity pain may also be a problem, due to inherent injury to the extremity or from neurological damage to the sensory pathways.

Injury to the brain can result in any number of changes in mental function, including changes in personality. The specific changes, of course, depend on the specific structures damaged. Very com­monly, brain-injured patients experience problems with memory, attention, and arousal, as well as difficulties with language and communication (Seel et al., 1997). Even patients who experience a relatively good recovery will often have subtle cognitive deficits that make returning to work or living independently difficult. A list of potential cognitive problems after TBI can be found in Table 13.2 (Groswasser & Stern, 1998).

Recovery from brain injury is a highly variable process. Severely injured patients recover in gen­eral along a set of stages, classified as the Rancho Los Amigos Scale of Cognitive Functioning (see Table 13.3). Patients do not always progress through each stage in a stepwise fashion; some patients may skip one or more stages. This scale has its greatest usefulness in communicating with other team members about the condition of the patient, although at times it is helpful for family members, particularly when patients are in an agitated state. Some families find it somewhat comforting to know that the agitated state is part of a normal recovery process following TBI.

Potential Cognitive Problems after TBI Rancho Los Amigos Scale of Cognitive Functioning—Revised Unresponsive: total assistanceComplete absence of change in behavior when presented any stimulus.Generalized response: total assistanceGeneralized reflex response to painful stimuli; may increase or decrease activity in response to repeated auditory stimuli; responds to external stimuli with generalized physiological changes; gross body movement; responses may be significantly delayed.Localized response: total assistanceWithdraws from painful stimuli; may turn away or toward auditory stimuli; may track object that passes across visual field or blink to visual threat. Responds inconsistently to simple commands; may respond to some people and not others.Agitated/

aggressive:

maximal

assistance

Alert, in heightened state of activity. Purposeful attempts to remove tubes and restraints; may exhibit aggressive or flight behavior. Emotionally labile, unable to cooperate with rehabilitation efforts. Verbalizations are incoherent and inappropriate to activity or environment.Confused-

inappropriate:

maximal

assistance

Alert, not agitated, disoriented. Frequent brief periods of nonpurposeful sustained attention. Severely impaired memory. Unable to learn new informtion. May demonstrate inappropriate use of external object. Able to converse on a social and automatic level for brief periods of time.Confused-

appropriate:

moderate

assistance

Inconsistently oriented to person, time, and place. Able to attend to highly familiar tasks in nondistracting environment for prolonged periods of time. Able to use memory aid with assistance. Begins to show carryover for relearned familiar tasks. Verbal conversations are appropriate in familiar and structured situations.Automatic-

appropriate:

minimal

assistance

Consistently oriented to person and place within highly familiar environments. Able to attend to highly familiar tasks in nondistracting environment for at least 30 minutes with minimal assistance to complete tasks. Minimal supervision for new learning. Shallow recall of personal activities. Superficial awareness of his/her condition but unaware of specific impairments and the limits they place on the ability to safely, accurately, and completely carry out household, work, and leisure ADLs.Purposeful-

appropriate:

standby

assistance

Consistently oriented to person, place, and time. Able to attend to and complete familiar tasks for 1 hour in distracting environment. Able to recall and integrate past and recent events. May be able to use memory aids with supervision; aware of impairments on a superficial level but needs assistance to undertake appropriate corrective action. May demonstrate low frustration tolerance, irritability, and become argumentative.

May be able to recognize socially inappropriate behavior and take corrective action with assistance.

Purposeful- appropriate: standby assistance on requestAble to independently shift back and forth between tasks and complete them accurately for at least 2 consecutive hours. Uses memory devices appropriately when reminded; may be able to initiate and carry out steps in familiar household, work, and leisure tasks with assistance when requested. Aware of and acknowledges impairments and disabilities when they interfere with task completion and takes appropriate corrective action with supervision when requested. May continue to have low frustration tolerance, irritability, and depression, but able to monitor social interaction more appropriately with only standby assistance. May be able to think about consequences of actions or decisions when requested.Purposeful-

appropriate:

modified

independent

Able to handle multiple tasks simultaneously in all environments but may require periodic breaks. Able to independently procure, create, and maintain own assistive memory devices. Independently initiates and carries out self-care, household, community, work, and leisure tasks, but may require more time or compensatory strategies to complete them. Able to independently think about the consequences of decisions or actions but may require more than the usual amount of time or compensatory strategies to select the appropriate decision or action. Social interactions are fairly consistently appropriate.

Most sources indicate that full neurological recovery of the brain following a severe injury takes approximately 1 year. Although this is a good estimate for most patients, there are certainly excep­tions, and some patients have demonstrated significant recovery even after 1 year. Researchers are learning more about the process of neuroplasticity and factors affecting better outcomes (Ginsberg et al., 1997; Pike & Hamm, 1997).

Impairments following brain injury may include almost any complication imaginable. However, there are certain impairments that occur with such regularity after TBI that they warrant special mention. These impairments are the main issues that cause long-term problems after brain injury. Any life care plan for a patient who is traumatically severely injured should be sure to address these particular issues.

¦    Weakness: Injury to the motor cortex or motor pathways may lead to weakness. Severe enough injury will result in paralysis. Weakness is usually the biggest factor affecting a person’s ability to perform activities of self-care, such as dressing, grooming, and feeding. It

may also impair an individual’s ability to walk and move about and, in extreme cases, may lead to the necessity of assistance with transfers.

¦     Spasticity: Spasticity, defined as “velocity-dependent increase in motor tone,” as mentioned earlier in the post, often remains a huge obstacle to independence after a brain injury. Spasticitiy is manifested clinically as an involuntary “tightening” of the muscles, resulting in difficulty moving a joint through normal range of motion. Spasticity is often associ­ated with weakness and further complicates the patient’s ability to move and perform activities of self-care. Furthermore, severe spasticity places the patient at risk for a number of other complications, such as contractures and skin breakdown. Much of the medical treatment following TBI centers around the prevention and treatment of spasticity. A number of medical interventions in the treatment of spasticity have become available in recent years. Aside from oral medications and therapeutic interventions such as splint­ing, casting, bracing, and range-of-motion exercises, patients are frequently treated with a variety of injections for spasticity. These may include nerve blocks using ethanol or phenol or, more commonly now, botulinum toxin injections. A newer treatment device, the intrathecal pump, may be surgically implanted to provide a higher concentration of medicine for spasticity directly at the level of the spinal cord, where it is most effective. The advantage to this technique is that it allows greater control over the administration of medicine, while avoiding many of the side effects associated with oral administration of medication. This treatment is not for everyone, however, and should be discussed with the patient’s doctor. Finally, various surgical techniques may be used, usually as last-resort efforts, for treatment of spasticity. These include various tendon-lengthening procedures, rhizotomy, or cordotomy.

¦     Behavioral problems: Although other issues may be more of a focus of medical treatment, it is often behavioral issues that prevent successful community reintegration and return to gainful employment. Patients may have low frustration tolerance, impaired judgment, and, in many cases, emotional lability or frank aggression that hinder successful rehabilita­tion outcomes. Behavioral problems are usually addressed on a number of levels, including psychological counseling, behavior modification plans, medications, and, in worst cases, inpatient neurobehavioral treatment programs.

¦     Cognitive: Several studies have examined the frequency of patients’ complaints following TBI. The most common complaint in all studies is problems with memory. Areas of the brain associated with memory formation are particularly susceptible to injury following trauma, due to their proximity to bony protuberances inside the skull. Additionally, these structures are particularly susceptible to anoxic injury as well, which can occur secondarily following trauma. Deficits in attention, motivation, and sensory input can also secondarily result in memory problems.

¦     Aging: As noted below in the vocational category, aging with a brain injury can result in a faster than average decline physically as well as cognitively. Reduced physical skills and judg­ment can also result in additional injury as time passes. Indeed, once a person has experienced a brain injury, he or she is much more likely to have a second injury than people without a brain injury. Also, for some mild to moderately brain-injured clients, social isolation and awareness of deficits eventually erode the hope and optimism that occur while progress is being made, and behavior and emotional problems may rise several years after the original insult. These problems are not as much related to aging as to the passage of time and the slow realization that they will never achieve their preinjury levels and may be unable to enjoy normal social and love relationships (Trudel & Purdum, 1998).

Successful return to the community remains a significant challenge given all of the potential barriers a patient may face due to the impairments sustained as a result of the injury (Berens, 2008; Smith- Knapp et al., 1996; Wall et al., 1998). With changes in personality, and behavioral problems, inter­personal relationships often become difficult. Many patients require ongoing supervision for safety reasons, which interferes with social activities. Driving a motor vehicle is a significant concern, and a formal driving evaluation should be performed by a therapist trained to look for the specific problems that may interfere with safe driving.

An additional issue frequently seen is return to recreational activities. A high percentage of brain injury patients engaged in high-risk activities prior to their injury (Chesnut et al., 1993). In fact, it is often engagement in high-risk activities that led to the brain injury in the first place. It is extremely important that individuals protect themselves against a second injury, particularly while the brain is healing. The second impact syndrome, in which a person healing from one injury is exposed to a second injury, may result in exponentially worse or even fatal outcomes, even with a relatively minor second injury. It is therefore extremely important that the patient be restricted from engaging in activities that may place him or her at risk for another injury. A therapeutic recreation specialist may be helpful in identifying and developing appropriate leisure interests after brain injury as well as helping develop techniques to pursue those interests when physical and cognitive impairments make them difficult. In addition, substance abuse may adversely affect recovery and ultimate outcome, further complicating the vocational and life care planning needs (Corrigan, 1995).

Return to gainful employment after brain injury remains a significant challenge (Dikmen et al., 1994; Goodall et al., 1994; Ip et al., 1995; Wehman et al., 1988, 1993; Stapleton et al., 1989; Cifu et al., 1997; Zasler, 1997). Most studies indicate that following a brain injury, approximately one-quarter to one-third of individuals return to work within a 1- to 2-year period following the injury (Traumatic Brain Injury National Data and Statistical Center, 2004). Even with milder brain injuries, work-related issues often become the major problem due to significant problems with interpersonal relationships and behavioral changes (Baker, 1990; Chwalisz, 1992; DePompei

&  Williams, 1994). Most TBIs occur in individuals between the ages of 16 and 30, a time in most people’s lives when education is being completed and career goals established. For those who have completed their education, the cognitive problems often prohibit the use of previously gained knowledge. Additionally, memory problems may make further education or training impossible, in the worst cases.

It is strongly recommended that individuals undergo a neuropsychological evaluation to deter­mine their capacity for education and work (Weed, 1996, 1998; Macciochi et al., 1998). A proper, thorough neuropsychological evaluation will give information about how the patient learns and processes information, and will help the vocational rehabilitation counselor in establishing appro­priate return-to-work goals. Many clients, in fact, are unable to return to competitive employment due to their impairments, or need significant support and assistance to do so. Many patients have no difficulty obtaining employment, but have a great deal of trouble maintaining employment.

In addition to the standard evaluation report, add the following as appropriate:Please describe, in layman terms, the injury to the brain.Please describe the effects of the accident on the client’s ability to function.Please provide an opinion to the following topics: Intelligence level? (include pre- vs. postincident if able)Personality style with regard to the workplace and home?Stamina level?Functional limitations and assets?Ability for education/training?Vocational implications—style of learning?Level of insight into present functioning?Ability to compensate for deficits?Ability to initiate action?

j. Memory impairments? (short-term, long-term, auditory, visual, etc.) k. Ability to identify and correct errors? l. Recommendations for compensation strategies? m. Need for companion or attendant care?

What is the proposed treatment plan? Counseling? (individual and family)Cognitive therapy?Reevaluations?Referral to others? (e.g., physicians)Other?How much and how long? (include cost per session or hour and reevaluations)Source: Roger O. Weed, with acknowledgment to Robert Frasier for some content.

Research regarding employment suggests that the most difficult to place long term are people with mental illness and brain injury.

In order to adequately assess the vocational and life planning needs of a person with a brain injury, it is recommended that, as clinical judgment dictates, other allied health professionals be considered. The occupational therapist may be an appropriate referral for an assessment for seating and positioning, adaptive aids, and other vocationally related issues. For some clients, activities of daily living training, including household safety, would be included. The speech and language pathologist will be instrumental in determining augmentative communications and assistive tech­nology for clients with more severe injuries, as well as in providing an assessment of receptive and expressive speech and language. They also often offer cognitive remediation strategies. A physical therapist is often the most appropriate referral to determine the client’s true physical capabilities by compiling a functional capacity assessment (or physical capacity assessment) that is more detailed than most physicians can report. For the young adult or pediatric case, an educational consultant can be very important to maximize the client’s educational potential. Under the Individuals with Disabilities Education Act (IDEA), the public school system is responsible for providing specialized services to children with disabilities. However, many of these clients are unserved for a variety of reasons. One reason is that the client has not been adequately assessed in order to identify deficits that would meet the criteria for specialized education. Another reason is that the client may meet the definition, but the school’s funding is inadequate and the school will fail to provide appropriate support. Educational consultants who are familiar with the rules often can negotiate the appropri­ate education protocol.

Several methods ofvocational assistance have been developed, including sheltered workshops and supported employment. The supported employment model involves a job coach who spends time with the patient at the worksite and assists with training the patient for the job, accommodations of the workspace if necessary, and helping with problems that may occur if needed. Much of the support involves educating the employer about the nature of brain injury (McMahon & Shaw, 1991; Wehman et al., 1993).

In addition, the effects of aging with a brain injury may affect work life expectancy (Weed, 1998). Data reveal that many clients with a brain injury cognitively or physically deteriorate at a faster rate and appear years older than their chronological age; it is not uncommon for clients to depart from work (i.e., retire early) at an age younger than that of most able-bodied workers. Reduced physical skills from the initial injury mean the person has less of a reserve than the aver­age person, so as he or she ages, he or she may reach the threshold of dependence at an earlier age. There also may be an increased risk of Alzheimer’s disease at an earlier age, leading to loss of inde­pendence earlier than with the average person (Chandra et al., 1989; Gedye et al., 1989; Rosenthal, 1990; Cifu et al., 1996b; Thompson et al., 1997). For example, it may be appropriate to phase out work and phase in a day program or volunteer activities by the time the client is in his or her fifties. The decline in work life can also be a result of moving from full-time to part-time work as well as earlier retirement.

Wine, Salt and Your Heart – Brain Health

ALCOHOL: A BLOOD PRESSURE HAZARD

Many experts call alcohol a widespread but largely unrec­ognized cause of high blood pressure. Some studies show that excessive drinking makes blood pressure soar, and that cutting back to moderate consumption may help. But new research suggests that drinking no alcohol at all is the best way to lower blood pressure. In one new study directed mostly at African-Americans, researchers found that drink­ing only one drink of alcohol per day significantly boosted both diastolic and systolic blood pressure.

Government researchers who conducted the famous blood-pressure-reducing DASH Diet also concluded that abstaining from alcohol is more apt to lower your blood pressure than drinking moderately.

ALCOHOL: THE HARM AND BENEFIT

Decidedly, drinking too much alcohol for too long can bring on a stroke. Drinking seven or more drinks a day triples your risk of having an ischemic (blood clot) stroke, accord­ing to new research by Ralph L. Sacco, Columbia Univer­sity College of Physicians and Surgeons in New York, who studied 677 stroke victims aged forty and older. However, he says heavy drinkers can reverse their higher risk by reducing intake to two drinks a day or quitting drinking entirely. On the other hand, moderate drinkers—up to two drinks per day—had a 45 percent lower risk of blood-clot stroke when compared with nondrinkers.

Other studies show that heavy drinking dramatically raises the risk of a bleeding or hemorrhagic stroke. Fur­ther, the amount of alcohol you drink may help determine the size of a stroke. The more you drink, the larger and more damaging the stroke, according to one recent analy­sis. Binge drinking is particularly risky, sometimes trigger­ing strokes, even in young people.

WINE VS. STROKES

There’s new evidence that people who drink wine appear to have a lower risk of strokes. Danish researcher Thomas Truelsen, M.D., at Copenhagen University Hospital, in a large study of thirteen thousand men and women over a period of sixteen years, found stroke odds 34 percent lower in those who drank one to six glasses of wine a week com­pared with those who drank wine not at all or infrequently. (About two-thirds of the wine consumed in Denmark is red wine.) Moderate drinkers of spirits had a 3 percent lower stroke risk. People who drank beer once a week or more had a 9 percent greater chance of suffering a stroke. As expected, heavy drinking was harmful. Six drinks a day or more raised stroke risk 50 percent.

How MUCH?

Moderate drinking is defined as one or two drinks per day for men and one drink for women and those older than age sixty-five. One drink is: a 12-ounce bottle of beer or a wine cooler; a 5-ounce glass of wine, or 1.5 ounces 80-proof dis­tilled spirits.

The issue of alcohol intake and disease prevention is a tricky one for physicians, who do not recommend that anyone take up drinking for his or her health. The physical and emotional damage wrought by alcohol abuse in this country is enormous, and light or mod­erate drinking is not possible for many people. . . . But because . . . alcohol appears to play a role in prevent­ing [heart disease] and now stroke, physicians advise people who drink small amounts to keep doing what they are doing . . . everything in moderation.”

—Harvard Health Letter, March 1999

Drinking seven or more drinks a day triples your risk of having an ischemic (blood clot) stroke. Former heavy drinkers who restrict drinking to no more than two drinks per day or quit entirely erase the added risk of stroke.

BOTTOM LINE: Drinking in moderation (one drink a day for women, no more than two for men), especially red wine, might help discourage a blood-clot type stroke. Heavy drinking or binge drinking is sure to be detrimental, helping bring on a stroke, especially a bleeding stroke. However, if you do not currently drink alcohol, do not start drinking as an anti-stroke mea­sure. Considering the downside of alcohol, there are many other safer ways to care for your brain and body, that can have a much greater impact in deterring a stroke.

SALT, STROKE, AND BLOOD PRESSURE

Overdosing on salt or sodium can boost blood pressure and stroke risk in many, but not all, people. Some, for genetic reasons, are more “salt sensitive,” meaning their vascular system reacts more vigorously when loaded with salt. If you are overweight, the odds are worse. Tulane University re­searchers recently found that an increase in sodium of a mere 100 mmol a day doubled the risk of fatal strokes among 2700 overweight men and women.

Japan is a striking case in point. Historically, the Japan­ese consume extraordinary amounts of sodium, for exam­ple in soy sauce and salted fish. They also historically have one of the highest rates of stroke in the world, particularly hemorrhagic or bleeding strokes. High sodium makes blood vessels in the brain more permeable and leaky, say

experts, and vulnerable to ruptures, spilling blood into the brain. A recent nationwide health initiative to lower blood pressure and intake of sodium has led to a decided drop in strokes among the Japanese, for the first time in recent his­tory.

DON’T DRINK ALCOHOL IF YOU:

Are pregnant or considering pregnancy.Have a medical condition that can be worsened by drinking such as an ulcer or liver diseaseHave a personal or family history of alcoholismAre taking medication that may interact with alcoholAre planning to drive or engage in other activi­ties that require you to be alertAre under the legal drinking age.

SOURCE: American Medical Association

Homocysteine and Brain Health

Beware Homocysteine—Potent Brain Toxin

An amino acid in your blood that few doctors even knew about until very recently is now considered a major factor in brain breakdown. It’s called homocysteine, and too much of it can accumulate in blood, helping clog and destroy blood vessels, including those that feed the brain; it may even damage mental acuity and mood by a direct toxic effect on brain cells. Luckily, homocysteine is a dragon easily slain by modest doses of B vitamins, which makes its continuing human destruction all the more appalling. High homocysteine, like high cholesterol, can be determined by a blood test.

Unquestionably, high homocysteine is incriminated in failing intellectual abilities. Tufts University researchers recently reported that middle-aged to elderly men with the highest homocysteine blood concentrations performed on one test of mental competence exactly like patients with mild Alzheimer’s disease! In fact, among the 25 percent with the highest homocysteine, only 22 percent could cor­rectly copy a cube and only 17 percent could copy a tapered box. About 75 percent of those with the lowest homocys­teine levels drew the figures correctly, as can most chil­dren by age thirteen. Such subnormal performances in older people indicate the brain has been damaged, said researchers.

BRAIN ALERT: As much as 40 percent of cere­brovascular disease appears tied to high homocys­teine levels.

High levels of homocysteine signify not only problems with memory, concentration, and thinking abilities, but also to low moods. Among a group of depressed persons, young and old, the higher the homocysteine, the lower the scores on mental acuity and mood assessment tests. In a recent study of outpatients with major depression, 20 per­cent had elevated homocysteine and 19 percent, low folic acid.

BOTTOM LINE: High blood levels of homocysteine pre­dict increased susceptibility to mental impairment and depression in both the old and young.

THE STROKE CONNECTION

Overwhelming evidence shows that high blood homocys­teine predicts strokes. A 1992 review of medical research (a meta-analysis) by Swedish researchers found that fully one-quarter of patients with cerebrovascular disease had high homocysteine. Angiograms of the carotid (neck) artery that feeds blood and oxygen to the brain revealed a blockage or closing in fully 85 percent of a group of patients with high homocysteine who had suffered a TIA (a prelude to stroke) or a minor stroke. In fact, homocys­teine is a stronger predictor of stroke than smoking, high blood pressure, or high cholesterol, revealed a large scale study of stroke victims by Swedish neurologist Dr. Lars E. Brattstrom at University Hospital in Lund. Forty percent who had strokes of all types—from an embolism, hemor­rhage, blockage, or carotid artery disease—had high homocysteine.

Similarly, British researchers studying 7,735 middle-aged men over a thirteen-year period found that the higher the homocysteine, the higher the stroke risk—regardless of weight, diabetes, cholesterol, high blood pressure, or smok­ing! Indeed, those with the highest homocysteine were about three times more apt to have a stroke than those with the lowest levels.

HOMOCYSTEINE PREDICTS ALZHEIMER’S

Also disturbing, high homocysteine is a sign you may be on the fast track for Alzheimer’s. A new study by Robert Clarke, M.D., of Oxford University in England, found that a high homocysteine reading raised odds of developing Alzheimer’s by an astounding 450 percent! Not surprisingly, those with Alzheimer’s also had low blood levels of folic acid and vita­min B12, which suppresses homocysteine. Low levels of folic acid tripled the odds of Alzheimer’s.

Even more alarming, the higher the blood homocysteine, the faster Alzheimer’s moved to destroy the brain. Homo­cysteine’s power to speed brain deterioration was seen on brain scans and on declining scores on mental and memory tests. Researchers visually charted the wasting away of spe­cific temporal lobes of the Alzheimer’s-diseased brains, and the higher the homocysteine, the greater the shrinkage. In those with the highest homocysteine, a specific brain lobe shrank about 20 percent in three years compared with only 5 percent in those with the lowest homocysteine. As expected, the progression of Alzheimer’s also was greatest in those with the lowest folic acid and B12.

How homocysteine promotes Alzheimer’s disease is not clearly understood, although recent evidence suggests the combination of disease in cerebral blood vessels and Alz­heimer’s interacts to worsen the brain damage. Further, high homocysteine may be a marker for low folic acid, thought to help protect the brain from Alzheimer’s.

BRAIN ALERT: High homocysteine triples your risk of stroke and quadruples your chances of Alzheimer’s disease.

How TO ZAP HOMOCYSTEINE

The cure for brain-damaging homocysteine is amazingly simple and inexpensive: B vitamins, notably folic acid. The absence of folic acid allows toxic homocysteine to pile up wildly in the blood. Folic acid breaks it down. Vitamins B6 and B12 also help dispose of homocysteine, but folic acid is by far the most powerful suppresser. Harvard investigators determined that at least two-thirds of high homocysteine is linked to low levels of folic acid. People who take multi­vitamins, typically containing 400 micrograms of folic acid, have much lower homocysteine than nonvitamin users.

Taking B vitamins can even stop and reverse homocys­teine’s purported damage to vital carotid arteries, according to a groundbreaking 1998 study by Canadian cardiologist J. David Spence, M.D., at the University of Toronto. He and colleagues measured the progressive closure and plaque buildup in the carotid neck arteries of thirty-eight men and women, average age fifty-eight, before and after taking B vitamins for four and a half years. The results were aston­ishing.

When not taking B vitamins, the subjects’ plaque area increased about 50 percent. After taking vitamins, the plaque actually decreased in size about 10 percent. In short, the vitamins acted as a kind of detergent to clean out arter­ies and reverse atherosclerosis. Dr. Spence’s study used a high dose of folic acid-2.5 milligrams—because a few peo­ple need that much to overcome a genetic predisposition to extra high homocysteine. However, he says 400 micro­grams of folic acid—a typical daily dose—curbs high homo­cysteine in most people. He also gave 250 micrograms B12 and 25 milligrams of B6.

Why is high homocysteine a villain in blood vessel and brain tissue damage? One theory: Homocysteine sets the stage in blood vessel linings for clotting and deposition of plaque, leading to damage and closure of vessels. In par­ticular, homocysteine incites artery cells to synthesize col­lagen, a major component in atherosclerotic plaques, which may also cause stiffening of the blood vessel. Second, homo­cysteine may block the synthesis of neurotransmitters, such as serotonin. Third, high homocysteine may act as a neu­rotoxin by triggering metabolic changes resulting in acti­vation of substances, such as glutamate, that directly injure and kill brain cells.

BRAIN ALERT: Only one in ten Americans gets the amount of folic acid needed to curb high homocys­teine, according to Harvard researchers.

EGGS AND HOMOCYSTEINE

Ironically, public health warnings against eggs, because of their high cholesterol, may actually aggravate the homo­cysteine problem. Egg yolks are one of the best sources of choline, a B vitamin. Studies in the 1950s showed that depriving animals of choline caused homocysteine levels to soar. Thus, shunning eggs in attempts to avoid heart dis­ease may in fact have worsened the risk by promoting high homocysteine levels. As it turns out, dietary cholesterol, as in eggs, is not a primary culprit in raising blood choles­terol.

FIVE WAYS TO LOWER BRAIN-BUSTING HOMOCYSTEINE

Take folic acid, B6, and B12 supplements. Experts generally advise 400 micrograms of folic acid a day to squelch homocysteine. Dutch investiga­tors recently found that 250 micrograms of folic acid lowered homocysteine by 11 percent in younger women, and 500 micrograms reduced it by 22 percent. It worked best against the high­est levels of homocysteine. Another large study found that people taking multiple vitamins with 400 micrograms of folic acid had 10 to 15 per­cent lower homocysteine than non-vitamin­takers. A few people with genetic factors may need higher doses, prescribed by a doctor. Most experts say 25 milligrams of B6 and 250 micro­grams of B12 are generally enough to suppress homocysteine.To keep a lid on homocysteine, you must con­tinue to take B vitamins. Stopping causes homo­cysteine to shoot up to abnormal levels again within four months or so.Eat foods high in folic acid, such as orange juice, legumes, green leafy vegetables, almonds, forti­fied cereals, and avocados. However, your body utilizes only half as much folic acid from food as from supplements. A recent study found that eating high folic acid foods alone did not ade­quately suppress high homocysteine in about two-thirds of a group of elderly subjects. Thus, folic acid supplements are essential.Restrict coffee to less than five cups daily. Recent Norwegian research found that homocysteine was 20 percent higher in people who drank more than nine cups of coffee compared with less than one cup daily. More than five cups daily may raise homocysteine, research suggests. Those who both smoked and drank lots of coffee had particularly high homocysteine.Go easy on meat. The body makes homocysteine from high protein foods, notably animal protein, explains Kilmer S. McCully, M.D., at the Veter­ans Affairs Medical Center in Providence and originator of the homocysteine theory. Protein-rich plant foods are okay because they usually contain enough B vitamins to curb homocys­teine, he adds.*Don’t smoke. Smoking suppresses folic acid lev­els, paving the way for excessive formation of homocysteine.