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35.5: Nervous System Disorders - Biology

35.5: Nervous System Disorders - Biology


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Skills to Develop

  • Describe the symptoms, potential causes, and treatment of several examples of nervous system disorders

A nervous system that functions correctly is a fantastically complex, well-oiled machine—synapses fire appropriately, muscles move when needed, memories are formed and stored, and emotions are well regulated. Unfortunately, each year millions of people in the United States deal with some sort of nervous system disorder. While scientists have discovered potential causes of many of these diseases, and viable treatments for some, ongoing research seeks to find ways to better prevent and treat all of these disorders.

Neurodegenerative Disorders

Neurodegenerative disorders are illnesses characterized by a loss of nervous system functioning that are usually caused by neuronal death. These diseases generally worsen over time as more and more neurons die. The symptoms of a particular neurodegenerative disease are related to where in the nervous system the death of neurons occurs. Spinocerebellar ataxia, for example, leads to neuronal death in the cerebellum. The death of these neurons causes problems in balance and walking. Neurodegenerative disorders include Huntington’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease and other types of dementia disorders, and Parkinson’s disease. Here, Alzheimer’s and Parkinson’s disease will be discussed in more depth.

Alzheimer’s Disease

Alzheimer’s disease is the most common cause of dementia in the elderly. In 2012, an estimated 5.4 million Americans suffered from Alzheimer’s disease, and payments for their care are estimated at $200 billion. Roughly one in every eight people age 65 or older has the disease. Due to the aging of the baby-boomer generation, there are projected to be as many as 13 million Alzheimer’s patients in the United States in the year 2050.

Symptoms of Alzheimer’s disease include disruptive memory loss, confusion about time or place, difficulty planning or executing tasks, poor judgment, and personality changes. Problems smelling certain scents can also be indicative of Alzheimer’s disease and may serve as an early warning sign. Many of these symptoms are also common in people who are aging normally, so it is the severity and longevity of the symptoms that determine whether a person is suffering from Alzheimer’s.

Alzheimer’s disease was named for Alois Alzheimer, a German psychiatrist who published a report in 1911 about a woman who showed severe dementia symptoms. Along with his colleagues, he examined the woman’s brain following her death and reported the presence of abnormal clumps, which are now called amyloid plaques, along with tangled brain fibers called neurofibrillary tangles. Amyloid plaques, neurofibrillary tangles, and an overall shrinking of brain volume are commonly seen in the brains of Alzheimer’s patients. Loss of neurons in the hippocampus is especially severe in advanced Alzheimer’s patients. Figure (PageIndex{1}) compares a normal brain to the brain of an Alzheimer’s patient. Many research groups are examining the causes of these hallmarks of the disease.

One form of the disease is usually caused by mutations in one of three known genes. This rare form of early onset Alzheimer’s disease affects fewer than five percent of patients with the disease and causes dementia beginning between the ages of 30 and 60. The more prevalent, late-onset form of the disease likely also has a genetic component. One particular gene, apolipoprotein E (APOE) has a variant (E4) that increases a carrier’s likelihood of getting the disease. Many other genes have been identified that might be involved in the pathology.

Link to Learning

Visit this website for video links discussing genetics and Alzheimer’s disease.

Unfortunately, there is no cure for Alzheimer’s disease. Current treatments focus on managing the symptoms of the disease. Because decrease in the activity of cholinergic neurons (neurons that use the neurotransmitter acetylcholine) is common in Alzheimer’s disease, several drugs used to treat the disease work by increasing acetylcholine neurotransmission, often by inhibiting the enzyme that breaks down acetylcholine in the synaptic cleft. Other clinical interventions focus on behavioral therapies like psychotherapy, sensory therapy, and cognitive exercises. Since Alzheimer’s disease appears to hijack the normal aging process, research into prevention is prevalent. Smoking, obesity, and cardiovascular problems may be risk factors for the disease, so treatments for those may also help to prevent Alzheimer’s disease. Some studies have shown that people who remain intellectually active by playing games, reading, playing musical instruments, and being socially active in later life have a reduced risk of developing the disease.

Parkinson’s Disease

Like Alzheimer’s disease, Parkinson’s disease is a neurodegenerative disease. It was first characterized by James Parkinson in 1817. Each year, 50,000-60,000 people in the United States are diagnosed with the disease. Parkinson’s disease causes the loss of dopamine neurons in the substantia nigra, a midbrain structure that regulates movement. Loss of these neurons causes many symptoms including tremor (shaking of fingers or a limb), slowed movement, speech changes, balance and posture problems, and rigid muscles. The combination of these symptoms often causes a characteristic slow hunched shuffling walk, illustrated in Figure (PageIndex{2}). Patients with Parkinson’s disease can also exhibit psychological symptoms, such as dementia or emotional problems.

Although some patients have a form of the disease known to be caused by a single mutation, for most patients the exact causes of Parkinson’s disease remain unknown: the disease likely results from a combination of genetic and environmental factors (similar to Alzheimer’s disease). Post-mortem analysis of brains from Parkinson’s patients shows the presence of Lewy bodies—abnormal protein clumps—in dopaminergic neurons. The prevalence of these Lewy bodies often correlates with the severity of the disease.

There is no cure for Parkinson’s disease, and treatment is focused on easing symptoms. One of the most commonly prescribed drugs for Parkinson’s is L-DOPA, which is a chemical that is converted into dopamine by neurons in the brain. This conversion increases the overall level of dopamine neurotransmission and can help compensate for the loss of dopaminergic neurons in the substantia nigra. Other drugs work by inhibiting the enzyme that breaks down dopamine.

Neurodevelopmental Disorders

Neurodevelopmental disorders occur when the development of the nervous system is disturbed. There are several different classes of neurodevelopmental disorders. Some, like Down Syndrome, cause intellectual deficits. Others specifically affect communication, learning, or the motor system. Some disorders like autism spectrum disorder and attention deficit/hyperactivity disorder have complex symptoms.

Autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Its severity differs from person to person. Estimates for the prevalence of the disorder have changed rapidly in the past few decades. Current estimates suggest that one in 88 children will develop the disorder. ASD is four times more prevalent in males than females.

Link to Learning

This video discusses possible reasons why there has been a recent increase in the number of people diagnosed with autism.

A characteristic symptom of ASD is impaired social skills. Children with autism may have difficulty making and maintaining eye contact and reading social cues. They also may have problems feeling empathy for others. Other symptoms of ASD include repetitive motor behaviors (such as rocking back and forth), preoccupation with specific subjects, strict adherence to certain rituals, and unusual language use. Up to 30 percent of patients with ASD develop epilepsy, and patients with some forms of the disorder (like Fragile X) also have intellectual disability. Because it is a spectrum disorder, other ASD patients are very functional and have good-to-excellent language skills. Many of these patients do not feel that they suffer from a disorder and instead think that their brains just process information differently.

Except for some well-characterized, clearly genetic forms of autism (like Fragile X and Rett’s Syndrome), the causes of ASD are largely unknown. Variants of several genes correlate with the presence of ASD, but for any given patient, many different mutations in different genes may be required for the disease to develop. At a general level, ASD is thought to be a disease of “incorrect” wiring. Accordingly, brains of some ASD patients lack the same level of synaptic pruning that occurs in non-affected people. In the 1990s, a research paper linked autism to a common vaccine given to children. This paper was retracted when it was discovered that the author falsified data, and follow-up studies showed no connection between vaccines and autism.

Treatment for autism usually combines behavioral therapies and interventions, along with medications to treat other disorders common to people with autism (depression, anxiety, obsessive compulsive disorder). Although early interventions can help mitigate the effects of the disease, there is currently no cure for ASD.

Attention Deficit Hyperactivity Disorder (ADHD)

Approximately three to five percent of children and adults are affected by attention deficit/hyperactivity disorder (ADHD). Like ASD, ADHD is more prevalent in males than females. Symptoms of the disorder include inattention (lack of focus), executive functioning difficulties, impulsivity, and hyperactivity beyond what is characteristic of the normal developmental stage. Some patients do not have the hyperactive component of symptoms and are diagnosed with a subtype of ADHD: attention deficit disorder (ADD). Many people with ADHD also show comorbitity, in that they develop secondary disorders in addition to ADHD. Examples include depression or obsessive compulsive disorder (OCD). Figure (PageIndex{3}) provides some statistics concerning comorbidity with ADHD.

The cause of ADHD is unknown, although research points to a delay and dysfunction in the development of the prefrontal cortex and disturbances in neurotransmission. According to studies of twins, the disorder has a strong genetic component. There are several candidate genes that may contribute to the disorder, but no definitive links have been discovered. Environmental factors, including exposure to certain pesticides, may also contribute to the development of ADHD in some patients. Treatment for ADHD often involves behavioral therapies and the prescription of stimulant medications, which paradoxically cause a calming effect in these patients.

Career Connection: Neurologist

Neurologists are physicians who specialize in disorders of the nervous system. They diagnose and treat disorders such as epilepsy, stroke, dementia, nervous system injuries, Parkinson’s disease, sleep disorders, and multiple sclerosis. Neurologists are medical doctors who have attended college, medical school, and completed three to four years of neurology residency.

When examining a new patient, a neurologist takes a full medical history and performs a complete physical exam. The physical exam contains specific tasks that are used to determine what areas of the brain, spinal cord, or peripheral nervous system may be damaged. For example, to check whether the hypoglossal nerve is functioning correctly, the neurologist will ask the patient to move his or her tongue in different ways. If the patient does not have full control over tongue movements, then the hypoglossal nerve may be damaged or there may be a lesion in the brainstem where the cell bodies of these neurons reside (or there could be damage to the tongue muscle itself).

Neurologists have other tools besides a physical exam they can use to diagnose particular problems in the nervous system. If the patient has had a seizure, for example, the neurologist can use electroencephalography (EEG), which involves taping electrodes to the scalp to record brain activity, to try to determine which brain regions are involved in the seizure. In suspected stroke patients, a neurologist can use a computerized tomography (CT) scan, which is a type of X-ray, to look for bleeding in the brain or a possible brain tumor. To treat patients with neurological problems, neurologists can prescribe medications or refer the patient to a neurosurgeon for surgery.

Link to Learning

This website allows you to see the different tests a neurologist might use to see what regions of the nervous system may be damaged in a patient.

​​​​​​Mental Illnesses

Mental illnesses are nervous system disorders that result in problems with thinking, mood, or relating with other people. These disorders are severe enough to affect a person’s quality of life and often make it difficult for people to perform the routine tasks of daily living. Debilitating mental disorders plague approximately 12.5 million Americans (about 1 in 17 people) at an annual cost of more than $300 billion. There are several types of mental disorders including schizophrenia, major depression, bipolar disorder, anxiety disorders and phobias, post-traumatic stress disorders, and obsessive-compulsive disorder (OCD), among others. The American Psychiatric Association publishes the Diagnostic and Statistical Manual of Mental Disorders (or DSM), which describes the symptoms required for a patient to be diagnosed with a particular mental disorder. Each newly released version of the DSM contains different symptoms and classifications as scientists learn more about these disorders, their causes, and how they relate to each other. A more detailed discussion of two mental illnesses—schizophrenia and major depression—is given below.

Schizophrenia

Schizophrenia is a serious and often debilitating mental illness affecting one percent of people in the United States. Symptoms of the disease include the inability to differentiate between reality and imagination, inappropriate and unregulated emotional responses, difficulty thinking, and problems with social situations. People with schizophrenia can suffer from hallucinations and hear voices; they may also suffer from delusions. Patients also have so-called “negative” symptoms like a flattened emotional state, loss of pleasure, and loss of basic drives. Many schizophrenic patients are diagnosed in their late adolescence or early 20s. The development of schizophrenia is thought to involve malfunctioning dopaminergic neurons and may also involve problems with glutamate signaling. Treatment for the disease usually requires antipsychotic medications that work by blocking dopamine receptors and decreasing dopamine neurotransmission in the brain. This decrease in dopamine can cause Parkinson’s disease-like symptoms in some patients. While some classes of antipsychotics can be quite effective at treating the disease, they are not a cure, and most patients must remain medicated for the rest of their lives.

Depression

Major depression affects approximately 6.7 percent of the adults in the United States each year and is one of the most common mental disorders. To be diagnosed with major depressive disorder, a person must have experienced a severely depressed mood lasting longer than two weeks along with other symptoms including a loss of enjoyment in activities that were previously enjoyed, changes in appetite and sleep schedules, difficulty concentrating, feelings of worthlessness, and suicidal thoughts. The exact causes of major depression are unknown and likely include both genetic and environmental risk factors. Some research supports the “classic monoamine hypothesis,” which suggests that depression is caused by a decrease in norepinephrine and serotonin neurotransmission. One argument against this hypothesis is the fact that some antidepressant medications cause an increase in norepinephrine and serotonin release within a few hours of beginning treatment—but clinical results of these medications are not seen until weeks later. This has led to alternative hypotheses: for example, dopamine may also be decreased in depressed patients, or it may actually be an increase in norepinephrine and serotonin that causes the disease, and antidepressants force a feedback loop that decreases this release. Treatments for depression include psychotherapy, electroconvulsive therapy, deep-brain stimulation, and prescription medications. There are several classes of antidepressant medications that work through different mechanisms. For example, monoamine oxidase inhibitors (MAO inhibitors) block the enzyme that degrades many neurotransmitters (including dopamine, serotonin, norepinephrine), resulting in increased neurotransmitter in the synaptic cleft. Selective serotonin reuptake inhibitors (SSRIs) block the reuptake of serotonin into the presynaptic neuron. This blockage results in an increase in serotonin in the synaptic cleft. Other types of drugs such as norepinephrine-dopamine reuptake inhibitors and norepinephrine-serotonin reuptake inhibitors are also used to treat depression.

Other Neurological Disorders

There are several other neurological disorders that cannot be easily placed in the above categories. These include chronic pain conditions, cancers of the nervous system, epilepsy disorders, and stroke. Epilepsy and stroke are discussed below.

Epilepsy

Estimates suggest that up to three percent of people in the United States will be diagnosed with epilepsy in their lifetime. While there are several different types of epilepsy, all are characterized by recurrent seizures. Epilepsy itself can be a symptom of a brain injury, disease, or other illness. For example, people who have intellectual disability or ASD can experience seizures, presumably because the developmental wiring malfunctions that caused their disorders also put them at risk for epilepsy. For many patients, however, the cause of their epilepsy is never identified and is likely to be a combination of genetic and environmental factors. Often, seizures can be controlled with anticonvulsant medications. However, for very severe cases, patients may undergo brain surgery to remove the brain area where seizures originate.

Stroke

A stroke results when blood fails to reach a portion of the brain for a long enough time to cause damage. Without the oxygen supplied by blood flow, neurons in this brain region die. This neuronal death can cause many different symptoms—depending on the brain area affected— including headache, muscle weakness or paralysis, speech disturbances, sensory problems, memory loss, and confusion. Stroke is often caused by blood clots and can also be caused by the bursting of a weak blood vessel. Strokes are extremely common and are the third most common cause of death in the United States. On average one person experiences a stroke every 40 seconds in the United States. Approximately 75 percent of strokes occur in people older than 65. Risk factors for stroke include high blood pressure, diabetes, high cholesterol, and a family history of stroke. Smoking doubles the risk of stroke. Because a stroke is a medical emergency, patients with symptoms of a stroke should immediately go to the emergency room, where they can receive drugs that will dissolve any clot that may have formed. These drugs will not work if the stroke was caused by a burst blood vessel or if the stroke occurred more than three hours before arriving at the hospital. Treatment following a stroke can include blood pressure medication (to prevent future strokes) and (sometimes intense) physical therapy.

Summary

Some general themes emerge from the sampling of nervous system disorders presented above. The causes for most disorders are not fully understood—at least not for all patients—and likely involve a combination of nature (genetic mutations that become risk factors) and nurture (emotional trauma, stress, hazardous chemical exposure). Because the causes have yet to be fully determined, treatment options are often lacking and only address symptoms.

Glossary

Alzheimer’s disease
neurodegenerative disorder characterized by problems with memory and thinking
attention deficit hyperactivity disorder (ADHD)
neurodevelopmental disorder characterized by difficulty maintaining attention and controlling impulses
autism spectrum disorder (ASD)
neurodevelopmental disorder characterized by impaired social interaction and communication abilities
epilepsy
neurological disorder characterized by recurrent seizures
major depression
mental illness characterized by prolonged periods of sadness
neurodegenerative disorder
nervous system disorder characterized by the progressive loss of neurological functioning, usually caused by neuron death
Parkinson’s disease
neurodegenerative disorder that affects the control of movement
schizophrenia
mental disorder characterized by the inability to accurately perceive reality; patients often have difficulty thinking clearly and can suffer from delusions

35.5 Nervous system disorders

A nervous system that functions correctly is a fantastically complex, well-oiled machine&mdashsynapses fire appropriately, muscles move when needed, memories are formed and stored, and emotions are well regulated. Unfortunately, each year millions of people in the United States deal with some sort of nervous system disorder. While scientists have discovered potential causes of many of these diseases, and viable treatments for some, ongoing research seeks to find ways to better prevent and treat all of these disorders.


Disorders of the nervous system may involve the following:

Vascular disorders, such as stroke, transient ischemic attack (TIA), subarachnoid hemorrhage, subdural hemorrhage and hematoma, and extradural hemorrhage

Infections, such as meningitis, encephalitis, polio, and epidural abscess

Structural disorders, such as brain or spinal cord injury, Bell's palsy, cervical spondylosis, carpal tunnel syndrome, brain or spinal cord tumors, peripheral neuropathy, and Guillain-Barré syndrome

Functional disorders, such as headache, epilepsy, dizziness, and neuralgia

Degeneration, such as Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), Huntington chorea, and Alzheimer disease


The 18 Most Common Nervous System Diseases

When the functioning or structure of the Nervous System is altered for some reason, diseases appear that can severely limit people’s lives.. In this article we will look at the 18 most common diseases of the Nervous System, which are the following:

1. Sclerosis

Sclerosis is a disease of the nervous system that can be of two types: multiple sclerosis o amyotrophic lateral sclerosis (ELA). Let’s see the characteristics of each one:

Multiple sclerosis

It is a degenerative and chronic disease. Its origin is autoimmune, and occurs when the axons of the cells of the nervous system (neurons) are progressively losing myelinMyelin is the substance that covers the axons, whose function is to transmit electrical impulses through the nervous system, quickly and efficiently.

Symptoms The most characteristic features of multiple sclerosis are: pain, tiredness, weakness, perceptual disturbances and muscular tension.

Amyotrophic lateral sclerosis (ALS)

The ALS is also progressive and neurodegenerative. In this case, the motor neurons of the brain and spinal cord are altered and progressively deteriorate. As a result, the muscles of the body cannot receive nerve impulses, which hinders and prevents voluntary movement.

People often remain in wheelchairsand finally die, as the heart and breathing cease to function.

2. Epilepsy

Epilepsy Involves Recurrence of Seizures (more than one must appear in order to be diagnosed). Its origin is due to a hyperactivation of certain groups of neurons. The most typical symptoms of epilepsy are: convulsions, loss of consciousness, weakness, lack of muscle control, etc.

3. Headaches

Headaches are intense headaches. They can be of different types:

3.1. Tension headaches

They’re the most common. In this case the pain resembles a band or a helmet that squeezes the whole head.

3.2. Headache in outbreaks

The pain in this case appears in only one eye “inside” it and around it.

3.3. Migraine

It is also a common headache its symptoms include, in addition to the headache: nausea and visual changes or disturbances.

3.4. Paranasal sinus headache

Here the pain is located behind the forehead and/or cheekbones.

4. Cerebrovascular Diseases

Cerebrovascular diseases par excellence are strokes (ACV), which occur when blood flow to a part of the brain stops. This leads to a lack of oxygen and nutrients in some areas of the brain. The result is temporary or permanent brain damage, depending on the severity of the injury.

5. Dementia

Dementia Involves Severe Impairment of Cognitive Functionssuch as memory, reasoning, attention, intellectual capacity, etc.

Usually appears at an advanced age (from the age of 65), and interferes significantly in the life of the person, since when dementia is in an advanced stage, the patient ceases to be autonomous for their activities of daily living. The most common cause of amnesia is Alzheimer’s disease.

6. Confinement syndrome

Seclusion syndrome is another, although less common, but very serious, disease of the nervous system. The person with this syndrome cannot move any part of the body (maximum the eyes and/or mouth), being completely paralyzed.

It’s like she’s locked in her own body. It is caused by an injury to the brainstem (e.g. a heart attack) in the area of the protuberance.

7. Mononeuropathies

Another of the diseases of the Nervous System are mononeuropathies, which involve damage to a single nerve of the SN. The symptoms involved are mainly loss of movement and/or sensitivity. The effects will depend on which nerve is affected.

8. Polyneuropathy

Polyneuropathies, on the other hand, are diseases caused by an affectation of several peripheral nerves, which is usually symmetrical. This affectation usually occurs simultaneously on the four extremities of the body.

9. Guillain-Barré syndrome

Guillain-Barré Syndrome is a serious disease of autoimmune origin.which occurs because the immune system attacks a part of the nervous system. As a result, the nerves become inflamed, resulting in muscle weakness and/or paralysis.

10. Neuralgias

Neuralgias are a type of pain, which often affects the nerves of the face, skull, or neck. It is caused by infection, irritation, or compression of these nerves. It is one of the most common diseases of the nervous system. It differs from headaches because in this case the pain appears in the face, and not in the head.

11. Tumors

The tumors are excessive and uncontrolled cell proliferation somewhere on the body. In this case, we’re talking about the brain and the spinal cord. Some examples of SN tumors are medulloblastomas, astrocytomas, glioblastomas, etc.

12. Infections

When infections appear in the nervous system, we also consider them to be diseases of the nervous system these affect the neurons and the structures of the SN. For example, HIV and syphilis, if left untreated, can end up damaging neurons and even causing neuronal death.

13. Trauma

Trauma, though. are not considered to be diseases per secan also end up damaging the neurons and nerves of the SN. They are due to the presence of strong blows. We are talking, for example, about head injuries (TCE) that affect the brain, and spinal cord injuries that affect the spinal cord.

The symptoms of TCE can vary, causing alterations in consciousness, memory, movement, personality, etc. Spinal cord injuries cause paralysis of the extremities (lower and/or upper) below the injury, in addition to other symptoms. They are caused by a severance or rupture of the nerves in the spinal cord.

14. Autonomic dysreflexia

This disease occurs as a result of a spinal cord injury. In addition, the autonomic nervous system becomes overactive, and blood pressure increases. This is the result of difficulties in regulating blood pressure below the spinal cord injury.

Bibliographic references

MedlinePlus. (2019). Guillain-Barré syndrome.

Netter, F. (1989). Nervous system. Anatomy and physiology. Barcelona: Salvat.

WHO (2000). ICD-10. International Classification of Diseases, tenth edition. Madrid Pan-American.

Rowland, L. (1995). (Ed.) Merritt”s Textbook of Neurology. Read&Febiger.


Concept in Action

Visit this website for video links discussing genetics and Alzheimer’s disease.

Unfortunately, there is no cure for Alzheimer’s disease. Current treatments focus on managing the symptoms of the disease. Because decrease in the activity of cholinergic neurons (neurons that use the neurotransmitter acetylcholine) is common in Alzheimer’s disease, several drugs used to treat the disease work by increasing acetylcholine neurotransmission, often by inhibiting the enzyme that breaks down acetylcholine in the synaptic cleft. Other clinical interventions focus on behavioral therapies like psychotherapy, sensory therapy, and cognitive exercises. Since Alzheimer’s disease appears to hijack the normal aging process, research into prevention is prevalent. Smoking, obesity, and cardiovascular problems may be risk factors for the disease, so treatments for those may also help to prevent Alzheimer’s disease. Some studies have shown that people who remain intellectually active by playing games, reading, playing musical instruments, and being socially active in later life have a reduced risk of developing the disease.

Figure 16.30. Compared to a normal brain (left), the brain from a patient with Alzheimer’s disease (right) shows a dramatic neurodegeneration, particularly within the ventricles and hippocampus. (credit: modification of work by “Garrando”/Wikimedia Commons based on original images by ADEAR: “Alzheimer’s Disease Education and Referral Center, a service of the National Institute on Aging”)


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35.5: Nervous System Disorders - Biology

In this section, you will explore the following questions:

  • What are examples of symptoms, causes, and treatments for several examples of nervous system disorders?

Connection for AP ® Courses

Information about disorders of the nervous system is out of scope for AP ® . A nervous system that functions correctly is a complex and well-oiled machine—synapses fire appropriately, muscle move when needed, memories are formed and stored, and emotions are well regulated. You can now appreciate what it takes for you to be able to read and comprehend the information in this textbook. Unfortunately, each year millions of people in the United States deal with some sort of disorder involving the nervous system. Neurodegenerative disorders are characterized by loss of nervous system functioning usually caused by the death of neurons examples include Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). Neurodevelopmental disorders occur when the development of the nervous system is disturbed examples include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, and major depression. Epilepsy and stroke also have neurological origins. Although scientists have discovered potential causes of many of these diseases, and effective treatments for some, ongoing research into the prevention and treatment of these disorders continues.

A nervous system that functions correctly is a fantastically complex, well-oiled machine—synapses fire appropriately, muscles move when needed, memories are formed and stored, and emotions are well regulated. Unfortunately, each year millions of people in the United States deal with some sort of nervous system disorder. While scientists have discovered potential causes of many of these diseases, and viable treatments for some, ongoing research seeks to find ways to better prevent and treat all of these disorders.

Neurodegenerative Disorders

Neurodegenerative disorders are illnesses characterized by a loss of nervous system functioning that are usually caused by neuronal death. These diseases generally worsen over time as more and more neurons die. The symptoms of a particular neurodegenerative disease are related to where in the nervous system the death of neurons occurs. Spinocerebellar ataxia, for example, leads to neuronal death in the cerebellum. The death of these neurons causes problems in balance and walking. Neurodegenerative disorders include Huntington’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease and other types of dementia disorders, and Parkinson’s disease. Here, Alzheimer’s and Parkinson’s disease will be discussed in more depth.

Alzheimer’s Disease

Alzheimer’s disease is the most common cause of dementia in the elderly. In 2012, an estimated 5.4 million Americans suffered from Alzheimer’s disease, and payments for their care are estimated at $200 billion. Roughly one in every eight people age 65 or older has the disease. Due to the aging of the baby-boomer generation, there are projected to be as many as 13 million Alzheimer’s patients in the United States in the year 2050.

Symptoms of Alzheimer’s disease include disruptive memory loss, confusion about time or place, difficulty planning or executing tasks, poor judgment, and personality changes. Problems smelling certain scents can also be indicative of Alzheimer’s disease and may serve as an early warning sign. Many of these symptoms are also common in people who are aging normally, so it is the severity and longevity of the symptoms that determine whether a person is suffering from Alzheimer’s.

Alzheimer’s disease was named for Alois Alzheimer, a German psychiatrist who published a report in 1911 about a woman who showed severe dementia symptoms. Along with his colleagues, he examined the woman’s brain following her death and reported the presence of abnormal clumps, which are now called amyloid plaques, along with tangled brain fibers called neurofibrillary tangles. Amyloid plaques, neurofibrillary tangles, and an overall shrinking of brain volume are commonly seen in the brains of Alzheimer’s patients. Loss of neurons in the hippocampus is especially severe in advanced Alzheimer’s patients. Figure 26.30 compares a normal brain to the brain of an Alzheimer’s patient. Many research groups are examining the causes of these hallmarks of the disease.

One form of the disease is usually caused by mutations in one of three known genes. This rare form of early onset Alzheimer’s disease affects fewer than five percent of patients with the disease and causes dementia beginning between the ages of 30 and 60. The more prevalent, late-onset form of the disease likely also has a genetic component. One particular gene, apolipoprotein E (APOE) has a variant (E4) that increases a carrier’s likelihood of getting the disease. Many other genes have been identified that might be involved in the pathology.

LINK TO LEARNING

Visit this website for video links discussing genetics and Alzheimer’s disease.

  1. Risk genes do not guarantee that a person will get Alzheimer’s disease.
  2. Risk genes account for <5% of Alzheimer’s cases.
  3. Risk genes directly cause a disease.
  4. Individuals with risk genes have symptoms that develop when an individual is in their 40s or 50s.

Unfortunately, there is no cure for Alzheimer’s disease. Current treatments focus on managing the symptoms of the disease. Because decrease in the activity of cholinergic neurons (neurons that use the neurotransmitter acetylcholine) is common in Alzheimer’s disease, several drugs used to treat the disease work by increasing acetylcholine neurotransmission, often by inhibiting the enzyme that breaks down acetylcholine in the synaptic cleft. Other clinical interventions focus on behavioral therapies like psychotherapy, sensory therapy, and cognitive exercises. Since Alzheimer’s disease appears to hijack the normal aging process, research into prevention is prevalent. Smoking, obesity, and cardiovascular problems may be risk factors for the disease, so treatments for those may also help to prevent Alzheimer’s disease. Some studies have shown that people who remain intellectually active by playing games, reading, playing musical instruments, and being socially active in later life have a reduced risk of developing the disease.

Parkinson’s Disease

Like Alzheimer’s disease, Parkinson’s disease is a neurodegenerative disease. It was first characterized by James Parkinson in 1817. Each year, 50,000-60,000 people in the United States are diagnosed with the disease. Parkinson’s disease causes the loss of dopamine neurons in the substantia nigra, a midbrain structure that regulates movement. Loss of these neurons causes many symptoms including tremor (shaking of fingers or a limb), slowed movement, speech changes, balance and posture problems, and rigid muscles. The combination of these symptoms often causes a characteristic slow hunched shuffling walk, illustrated in Figure 26.31. Patients with Parkinson’s disease can also exhibit psychological symptoms, such as dementia or emotional problems.

Although some patients have a form of the disease known to be caused by a single mutation, for most patients the exact causes of Parkinson’s disease remain unknown: the disease likely results from a combination of genetic and environmental factors (similar to Alzheimer’s disease). Post-mortem analysis of brains from Parkinson’s patients shows the presence of Lewy bodies—abnormal protein clumps—in dopaminergic neurons. The prevalence of these Lewy bodies often correlates with the severity of the disease.

There is no cure for Parkinson’s disease, and treatment is focused on easing symptoms. One of the most commonly prescribed drugs for Parkinson’s is L-DOPA, which is a chemical that is converted into dopamine by neurons in the brain. This conversion increases the overall level of dopamine neurotransmission and can help compensate for the loss of dopaminergic neurons in the substantia nigra. Other drugs work by inhibiting the enzyme that breaks down dopamine.

EVERYDAY CONNECTION FOR AP® COURSES

  1. ALS degenerates sensory neurons that control voluntary muscle movement. As the lateral portion of the spine that controls muscle movement hardens, signals are no longer sent to muscles. Initially, muscles weaken but coordination is not effected, and eventually paralysis occurs.
  2. ALS degenerates motor neurons that control voluntary muscle movement. As the lateral portion of the spine that controls muscle movement hardens, signals are no longer sent to muscles. Initially, muscles strengthen and coordination is effected, and eventually paralysis occurs.
  3. ALS degenerates sensory neurons that control voluntary muscle movement. As the lateral portion of the spine that controls muscle movement hardens, signals are no longer sent to muscles. Initially, muscles weaken and coordination is effected, and eventually paralysis occurs.
  4. ALS degenerates motor neurons that control voluntary muscle movement. As the lateral portion of the spine that controls muscle movement hardens, signals are no longer sent to muscles. Initially, muscles weaken and coordination is effected, and eventually paralysis occurs.

Neurodevelopmental Disorders

Neurodevelopmental disorders occur when the development of the nervous system is disturbed. There are several different classes of neurodevelopmental disorders. Some, like Down Syndrome, cause intellectual deficits. Others specifically affect communication, learning, or the motor system. Some disorders like autism spectrum disorder and attention deficit/hyperactivity disorder have complex symptoms.

Autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Its severity differs from person to person. Estimates for the prevalence of the disorder have changed rapidly in the past few decades. Current estimates suggest that one in 88 children will develop the disorder. ASD is four times more prevalent in males than females.

LINK TO LEARNING

This video discusses possible reasons why there has been a recent increase in the number of people diagnosed with autism.

  1. diagnostic criteria changed
  2. increased vaccination rates
  3. more young parents reproducing
  4. decreased ascertainment across classes

A characteristic symptom of ASD is impaired social skills. Children with autism may have difficulty making and maintaining eye contact and reading social cues. They also may have problems feeling empathy for others. Other symptoms of ASD include repetitive motor behaviors (such as rocking back and forth), preoccupation with specific subjects, strict adherence to certain rituals, and unusual language use. Up to 30 percent of patients with ASD develop epilepsy, and patients with some forms of the disorder (like Fragile X) also have intellectual disability. Because it is a spectrum disorder, other ASD patients are very functional and have good-to-excellent language skills. Many of these patients do not feel that they suffer from a disorder and instead think that their brains just process information differently.

Except for some well-characterized, clearly genetic forms of autism (like Fragile X and Rett’s Syndrome), the causes of ASD are largely unknown. Variants of several genes correlate with the presence of ASD, but for any given patient, many different mutations in different genes may be required for the disease to develop. At a general level, ASD is thought to be a disease of “incorrect” wiring. Accordingly, brains of some ASD patients lack the same level of synaptic pruning that occurs in non-affected people. In the 1990s, a research paper linked autism to a common vaccine given to children. This paper was retracted when it was discovered that the author falsified data, and follow-up studies showed no connection between vaccines and autism.

Treatment for autism usually combines behavioral therapies and interventions, along with medications to treat other disorders common to people with autism (depression, anxiety, obsessive compulsive disorder). Although early interventions can help mitigate the effects of the disease, there is currently no cure for ASD.

Attention Deficit Hyperactivity Disorder (ADHD)

Approximately three to five percent of children and adults are affected by attention deficit/hyperactivity disorder (ADHD). Like ASD, ADHD is more prevalent in males than females. Symptoms of the disorder include inattention (lack of focus), executive functioning difficulties, impulsivity, and hyperactivity beyond what is characteristic of the normal developmental stage. Some patients do not have the hyperactive component of symptoms and are diagnosed with a subtype of ADHD: attention deficit disorder (ADD). Many people with ADHD also show comorbitity, in that they develop secondary disorders in addition to ADHD. Examples include depression or obsessive compulsive disorder (OCD). Figure 26.33 provides some statistics concerning comorbidity with ADHD.

The cause of ADHD is unknown, although research points to a delay and dysfunction in the development of the prefrontal cortex and disturbances in neurotransmission. According to studies of twins, the disorder has a strong genetic component. There are several candidate genes that may contribute to the disorder, but no definitive links have been discovered. Environmental factors, including exposure to certain pesticides, may also contribute to the development of ADHD in some patients. Treatment for ADHD often involves behavioral therapies and the prescription of stimulant medications, which paradoxically cause a calming effect in these patients.

CAREER CONNECTION

Neurologist

Neurologists are physicians who specialize in disorders of the nervous system. They diagnose and treat disorders such as epilepsy, stroke, dementia, nervous system injuries, Parkinson’s disease, sleep disorders, and multiple sclerosis. Neurologists are medical doctors who have attended college, medical school, and completed three to four years of neurology residency.

When examining a new patient, a neurologist takes a full medical history and performs a complete physical exam. The physical exam contains specific tasks that are used to determine what areas of the brain, spinal cord, or peripheral nervous system may be damaged. For example, to check whether the hypoglossal nerve is functioning correctly, the neurologist will ask the patient to move his or her tongue in different ways. If the patient does not have full control over tongue movements, then the hypoglossal nerve may be damaged or there may be a lesion in the brainstem where the cell bodies of these neurons reside (or there could be damage to the tongue muscle itself).

Neurologists have other tools besides a physical exam they can use to diagnose particular problems in the nervous system. If the patient has had a seizure, for example, the neurologist can use electroencephalography (EEG), which involves taping electrodes to the scalp to record brain activity, to try to determine which brain regions are involved in the seizure. In suspected stroke patients, a neurologist can use a computerized tomography (CT) scan, which is a type of X-ray, to look for bleeding in the brain or other health conditions. To treat patients with neurological problems, neurologists can prescribe medications or refer the patient to a neurosurgeon for surgery.

LINK TO LEARNING

This website allows you to see the different tests a neurologist might use to see what regions of the nervous system may be damaged in a patient.

  1. placing a 128 Hz tuning fork over a bone
  2. tapping a muscle tendon with a reflex hammer
  3. asking a patient to follow commands
  4. asking a patient to follow a target through different positions

Mental Illnesses

Mental illnesses are nervous system disorders that result in problems with thinking, mood, or relating with other people. These disorders are severe enough to affect a person’s quality of life and often make it difficult for people to perform the routine tasks of daily living. Debilitating mental disorders plague approximately 12.5 million Americans (about 1 in 17 people) at an annual cost of more than $300 billion. There are several types of mental disorders including schizophrenia, major depression, bipolar disorder, anxiety disorders and phobias, post-traumatic stress disorders, and obsessive-compulsive disorder (OCD), among others. The American Psychiatric Association publishes the Diagnostic and Statistical Manual of Mental Disorders (or DSM), which describes the symptoms required for a patient to be diagnosed with a particular mental disorder. Each newly released version of the DSM contains different symptoms and classifications as scientists learn more about these disorders, their causes, and how they relate to each other. A more detailed discussion of two mental illnesses—schizophrenia and major depression—is given below.

Schizophrenia

Schizophrenia is a serious and often debilitating mental illness affecting one percent of people in the United States. Symptoms of the disease include the inability to differentiate between reality and imagination, inappropriate and unregulated emotional responses, difficulty thinking, and problems with social situations. People with schizophrenia can suffer from hallucinations and hear voices they may also suffer from delusions. Patients also have so-called “negative” symptoms like a flattened emotional state, loss of pleasure, and loss of basic drives. Many schizophrenic patients are diagnosed in their late adolescence or early 20s. The development of schizophrenia is thought to involve malfunctioning dopaminergic neurons and may also involve problems with glutamate signaling. Treatment for the disease usually requires antipsychotic medications that work by blocking dopamine receptors and decreasing dopamine neurotransmission in the brain. This decrease in dopamine can cause Parkinson’s disease-like symptoms in some patients. While some classes of antipsychotics can be quite effective at treating the disease, they are not a cure, and most patients must remain medicated for the rest of their lives.

Depression

Major depression affects approximately 6.7 percent of the adults in the United States each year and is one of the most common mental disorders. To be diagnosed with major depressive disorder, a person must have experienced a severely depressed mood lasting longer than two weeks along with other symptoms including a loss of enjoyment in activities that were previously enjoyed, changes in appetite and sleep schedules, difficulty concentrating, feelings of worthlessness, and suicidal thoughts. The exact causes of major depression are unknown and likely include both genetic and environmental risk factors. Some research supports the “classic monoamine hypothesis,” which suggests that depression is caused by a decrease in norepinephrine and serotonin neurotransmission. One argument against this hypothesis is the fact that some antidepressant medications cause an increase in norepinephrine and serotonin release within a few hours of beginning treatment—but clinical results of these medications are not seen until weeks later. This has led to alternative hypotheses: for example, dopamine may also be decreased in depressed patients, or it may actually be an increase in norepinephrine and serotonin that causes the disease, and antidepressants force a feedback loop that decreases this release. Treatments for depression include psychotherapy, electroconvulsive therapy, deep-brain stimulation, and prescription medications. There are several classes of antidepressant medications that work through different mechanisms. For example, monoamine oxidase inhibitors (MAO inhibitors) block the enzyme that degrades many neurotransmitters (including dopamine, serotonin, norepinephrine), resulting in increased neurotransmitter in the synaptic cleft. Selective serotonin reuptake inhibitors (SSRIs) block the reuptake of serotonin into the presynaptic neuron. This blockage results in an increase in serotonin in the synaptic cleft. Other types of drugs such as norepinephrine-dopamine reuptake inhibitors and norepinephrine-serotonin reuptake inhibitors are also used to treat depression.

Other Neurological Disorders

There are several other neurological disorders that cannot be easily placed in the above categories. These include chronic pain conditions, cancers of the nervous system, epilepsy disorders, and stroke. Epilepsy and stroke are discussed below.

Epilepsy

Estimates suggest that up to three percent of people in the United States will be diagnosed with epilepsy in their lifetime. While there are several different types of epilepsy, all are characterized by recurrent seizures. Epilepsy itself can be a symptom of a brain injury, disease, or other illness. For example, people who have intellectual disability or ASD can experience seizures, presumably because the developmental wiring malfunctions that caused their disorders also put them at risk for epilepsy. For many patients, however, the cause of their epilepsy is never identified and is likely to be a combination of genetic and environmental factors. Often, seizures can be controlled with anticonvulsant medications. However, for very severe cases, patients may undergo brain surgery to remove the brain area where seizures originate.

Stroke

A stroke results when blood fails to reach a portion of the brain for a long enough time to cause damage. Without the oxygen supplied by blood flow, neurons in this brain region die. This neuronal death can cause many different symptoms—depending on the brain area affected— including headache, muscle weakness or paralysis, speech disturbances, sensory problems, memory loss, and confusion. Stroke is often caused by blood clots and can also be caused by the bursting of a weak blood vessel. Strokes are extremely common and are the third most common cause of death in the United States. On average one person experiences a stroke every 40 seconds in the United States. Approximately 75 percent of strokes occur in people older than 65. Risk factors for stroke include high blood pressure, diabetes, high cholesterol, and a family history of stroke. Because a stroke is a medical emergency, patients with symptoms of a stroke should immediately go to the emergency room, where they can receive drugs that will dissolve any clot that may have formed. These drugs will not work if the stroke was caused by a burst blood vessel or if the stroke occurred more than three hours before arriving at the hospital. Treatment following a stroke can include blood pressure medication (to prevent future strokes) and (sometimes intense) physical therapy.


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Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

Organizations Providing General Support


In Her Lifetime: Female Morbidity and Mortality in Sub-Saharan Africa (1996)

The evidence available for Sub-Saharan Africa suggests that the burden of nervous system disorders may be heavier in African communities than in comparable communities in other parts of the developing world (Osuntokun, 1970, 1971a Spillane, 1973). There is also evidence that the burden of certain of these disorders may be heavier in females than in males. Because of their particular significance for females, it is these disorders, presented in Table 5-1, that are the focus of this chapter. They are: toxic and nutritional disorders, headache syndromes, cerebrovascular diseases associated with oral contraceptive use, epilepsies, demyelinating diseases, neurologic complications of collagen diseases, and impaired cognition and dementia. An exception to this picture of gender-distinctive burden is cerebral malaria, potentially a greater problem for females because of their heightened susceptibility during pregnancy. This condition is discussed in-depth in Chapters 4 and 10.

LIFE SPAN PERSPECTIVE

The female, like the male, is at risk of suffering from specific disorders of the nervous system at certain stages of life, although disease onset for a number of these disorders occurs over a wide spectrum of age. Table 5-2 provides a listing of nervous system disorders, by age category, that affect both African males and females.

Because many of the nervous system disorders listed in Table 5-2 are believed to affect males and females equally over the life span, they are not discussed in this chapter. Other illnesses, such as tetanus and cerebral malaria, are reviewed elsewhere in this report (see Chapters 4 and 10, respectively). As noted above, this chapter focuses on the following nervous system disorders for which African females appear to be particularly susceptible or at risk: toxic and nutritional disorders, headache syndromes, cerebrovascular diseases associated with use of oral contraceptives, epilepsies, demyelinating diseases, neurologic complications of collagen diseases, and impaired cognition and dementia. The evidence for these disorders is presented below.

TOXIC AND NUTRITIONAL DISORDERS OF THE NERVOUS SYSTEM

Nutritional syndromes involving the nervous system are common in Sub-Saharan Africa. Protein-energy malnutrition may afflict 40 percent or more of preschool children at a stage when the maturation of the nervous system is still under way, and malnutrition can result in long-term or permanent damage to cognition and intellect

TABLE 5-1 Nervous System Disorders in Sub-Saharan Africa: Gender-Related Burden

Greater for Females than for Males

Burden for Females and Males Comparable, but of Particular Significance for Females

Cerebrovascular diseases associated with oral contraceptive use

Impaired cognition and dementia

Neurologic complications of collagen diseases

Toxic and nutritional disorders

NOTE: Significance is defined here as having impact on health that, for any reason&mdashbiological, reproductive, sociocultural, or economic &mdashis different in its implications for females than for males.

(de Mota et al., 1990 Grantham-McGregor et al., 1991 Lucas et al., 1990 Osuntokun 1972a Pollitt and Thompson, 1977 Rush, 1984 Smart, 1986 Stocks et al., 1982).

Onset of nutritional and toxic diseases of the nervous system, which include the tropical myeloneuropathies (Roman et al., 1987), are known to be precipitated by pregnancy and lactation. Wernicke's encephalopathy, caused by thiamine deficiency, is a known complication of severe morning sickness during pregnancy (hyperemesis gravidarum) and anorexia nervosa. Females also appear highly susceptible to effects of thiaminases in seasonal foods, such as those from the worm anaphe venata, commonly eaten in southwestern Nigeria and postulated as an etiological factor in seasonal epidemic ataxia (Ademolekun, 1993 Osuntokun, 1972b).

Folate and iron deficiencies, often associated with pregnancy and lactation, may be important determinants of fetal morbidity and mortality in the Sub-Saharan region. During pregnancy there is a greater requirement for folate because of the increased rate of folate metabolism (McParklin et al., 1993). Folate deficiency is widespread in African women and can contribute to a variety of neuropsychiatric syndromes, including peripheral neuropathy, dementia, and depression. The incidence of neural tube defects caused by folic acid deficiency could be as high as 7 per 1,000 deliveries (Airede, 1992), and may well be increasing in areas where maternal malnutrition has increased and folate deficits are significant. It is now well established that periconceptional folate supplementation could prevent first occurrence of neural tube defects (Czeizel and Dudas, 1992 MRC Vitamin Study Research Group, 1991). There is also greater need for folate in subjects with chronic hemolytic disease, such as hemoglobin sickle-cell disease, which afflicts about 1 percent of the West African population, and malaria.

Iron-deficiency is particularly common in Sub-Saharan Africa, and more common in females than in males. A major cause of iron-deficiency is hookworm infection, which afflicts millions of black Africans, especially in rural areas. Hookworm anemia is often unrecognized as an underlying cause of high maternal morbidity and mortality, apathy and poor health in children, and easy fatigability and impaired working capacity in adults (Pawlowski et al., 1991). Menorrhagia and pregnancy states predispose to iron-deficiency anemia. Other risk factors for iron-deficiency are the growth spurt of adolescence, with the accompanying burden of providing iron for an increased red cell mass and increased hemoglobin concentration childhood, especially between the ages of 4 months and 3

TABLE 5-2 Disorders of the Nervous System in the African Female Across Her Life Span

Congenital malformations from maternal malnutrition and infections

Cretinism from maternal iodine deficiency and goitrogenic diet, including cassava diet

Low birthweight from maternal malnutrition may cause poor neurodevelopment, increased occurrence or risk in later life of high blood pressure and mortality from cardiovascular disease, including stroke (Barker et al., 1989a,b Edwards et al., 1993 Law et al., 1993, 1991 Seldman et al., 1991 Whincup et al., 1989)

Impaired neurodevelopment from malnutrition

Meningitides, encephalitides (including parainfectious encephalomyelitis), poliomyelitis

Meningitides and encephalitides (including parainfectious encephalomyelitis), poliomyelitis

Lymphomas (especially Burkitt's) of nervous system

Meningitides and encephalitides, cerebral abscess

Meningitides, encephalitides, trypanosomiasis, cerebral malaria

Nutritional and toxic myeloneuropathies and peripheral nerve disorders

Nervous system involvement from choriocarcinoma

Polymyositis, myasthenia gravis

Demyelinating diseases (often monophasic, as Devic's disease)

Neurological complications of snake bites

Menopause/late adulthood (46&ndash65 years)

Nutritional and toxic myeloneuropathies and peripheral nerve disorders

Spinal cord and spinal nerve root disorders secondary to osteodegenerative disease of vertebral column

Brain and spinal cord neoplasms (primary and secondary)

Polymyalgia rheumatica, temporal arteritis

Spinal cord and spinal nerve root disorders secondary to osteodegenerative disease of the vertebral column (spine)

Brain and spinal cord neoplasms

years, with the rapid rate of growth and increase in red cell mass and diets consisting primarily of whole grain cereal and legumes with a rich iron content that is not readily absorbable. With the vital role of iron in the fundamental metabolism of the cells (including the neurons), it is not surprising that increasing evidence indicates that impaired psychomotor development and intellectual performance and changes in behavior result from even mild iron-deficiency, particularly in infants between 6 months and 2 years of age (Lozoff, 1988). Such infants showed significant decreases in responsiveness and activity, increased body tension, fearfulness, and tendency to fatigue (Lozoff et al., 1982a,b Oski et al., 1983 Walter et al., 1983), and there is some evidence that these abnormalities may persist after correction of iron-deficiency.

The deficiency of riboflavin common in African women has been associated with endogenous and neurotic depression, and pyridoxine deficiency has been linked to peripheral neuropathy and affective illness (Carney, 1990). Use of oral contraceptives also contributes to pyridoxine deficiency and may increase existing nutrition-related deficits (Stamp, 1993).

In some parts of Africa, endemic cretinism is widespread and is the result of iodine deficiency, further conditioned by a cassava diet. A neurodegenerative syndrome linked to a cassava diet is also endemic in some countries (Monekosso and Wilson, 1966 Osuntokun, 1968, 1981b) and occurs in epidemics, especially at times of drought, as reported from Mozambique, Tanzania, and Zaire (Carton et al., 1986 Cliff et al., 1986 Essers et al., 1992 Howlett et al., 1990, 1992 Mozambique, Ministry of Health, 1984 Rosling, 1986 Rosling et al., 1988 Tylleskar et al., 1992). Evidence that indicates a disproportionate occurrence of these disorders in females is lacking.

Poor nutritional status may also enhance the neurotoxicity of the cyanogenic glycosides, found in cassava, manihot, millet, and other dietary items commonly consumed in some parts of Sub-Saharan Africa (Osuntokun, 1968, 1981b) the organophosphates commonly used as pesticides and some frequently used drugs, including isoniazid, ethambutol, nitrous oxide, chloramphenicol, metronidazole, phenytoin, dapsone, chloroquine, vincristine, and nitrofurantoin (Osuntokun, 1986). Again, there are no data indicating an unusual burden of these disorders in females.

HEADACHE SYNDROMES

The prevalence of headache syndromes exceeds 50 percent, and the incidence of migraine is 6 percent or higher even in rural communities (Joubert, 1992 Levy, 1983 Lisk, 1987 Longe and Osuntokun, 1988 Osuntokun and Osuntokun, 1972 Osuntokun et al., 1982b,c, 1987b, 1992b). In some parts of Africa, migraine and tension headache are the most common modes of presentation of headache, in the community as well as in the hospital (Osuntokun, 1971b).

Migraine

Both common and classical migraine are predominantly diseases of women, with female-to-male ratios ranging from 5:2 in hospital case series, to 2:1 in two rural communities, and 6:5 in urban community studies in Nigeria. In one Nigerian study, in a sample of 19,000 people, the female predominance was high in patients under the age of 30 years, but the age-specific incidence rates in males and females over age 30 were comparable (Osuntokun et al., 1992b see Table 5-3 below).

A community-based study among the Zulus in Natal, South Africa, found a prevalence of migraine of 8.8 percent, with a female-to-male ratio of 10:1 (Joubert, 1992). Evidence suggests that migraine, particularly common migraine as defined by the International Headache Society (IHS, 1988), is influenced by hormonal changes associated with menarche, ovulation, and menstruation, which may account for the increased susceptibility of females to migrainous headaches. Contraceptive pills may also precipitate migraine, which may then continue despite stopping the pills. The relationship of migraine to hormonal levels is complex: some individuals experience reduction in migraine during pregnancy in others, the headaches are worse and in a third group, the headaches reappear soon after childbirth. Unlike Caucasian patients, who suffer from cluster headaches with a male-to-female ratio of 5:1 or higher, Nigerian females outnumber males among patients with cluster headaches

TABLE 5-3 Migrainous Headaches in Nigerian Africans&mdashAge-Specific Prevalence Ratios

(Osuntokun, 1971b Osuntokun et al., 1982a). Nigerian migraine sufferers with hemoglobin AS genotype (usually symptomless, apart from being susceptible to painless hematuria from is chemicrenal papillitis) are significantly liable to suffer from complicated migraine (Osuntokun and Osuntokun, 1972). HBAS has a frequency of 25 percent in West Africans. Among Nigerian migraine sufferers, the relative risk of epilepsy ranged from 2 to 3.2 (Osuntokun, 1971a Osuntokun et al., 1982b). Among Caucasians, epilepsy is said to be two to six times more common in people who suffer migraines compared with people who do not (Basser,1969 Hannington, 1974).

Tension Headache

As in Caucasians, there is an excess of females among Africans who suffer from tension headaches as defined by the IHS. In the Zulu study, all 19 patients who suffered from tension headache were females (Joubert, 1992). Among Nigerians, tension headache is twice as frequent as migraine (Osuntokun, 1971a,b), in contrast to subjects in the Zulu study, who experienced migraine with nearly four times the frequency of tension headache (Joubert, 1988 1992).

CEREBROVASCULAR DISEASES AND USE OF ORAL CONTRACEPTIVES

Cerebrovascular disease, such as stroke (subarachnoid hemorrhage, cerebral hemorrhage, cerebral infarction, hypertensive encephalopathy), is now as common in most communities in Africa as in the developed countries (Abraham and Abdulkadir, 1981 Bahemuka, 1989 Danesi et al., 1983 Lester, 1982 Matenga et al., 1986 Putterpill et al., 1984). In a community-based study in Nigeria, the age-specific incidence rates of stroke or cerebrovascular accident were comparable to rates in the Caucasian populations in Europe and among the Japanese (Osuntokun et al., 1979). Some analysis has suggested that the age-adjusted mortality rate for stroke in a Nigerian community may surpass that of the United States (Osuntokun, et al., 1987b). In Ethiopia, Ghana, Kenya, Nigeria, Senegal, and Uganda, stroke constitutes between 4 and 10 percent of all causes of death (Osuntokun, 1980).

Since the mid-1960s, a vast amount of epidemiologic, clinical, and laboratory evidence in developed countries has linked the current use of combined oral contraceptives with certain types of cardiovascular disease (CVD), especially venous thromboembolism, thrombotic stroke, myocardial infarction, subarachnoid hemorrhage, and hypertension (Irey et al., 1978 Lancet, 1979 Stadel, 1981 Thorgood et al., 1981 Vessey, 1982). Whether these findings from the developed countries can be extrapolated to black African countries is debatable. To date, no valid epidemiologic data link the use of the oral contraceptives by black Africans to increased CVD risk, although it is unlikely that the metabolic changes (Fotherby, 1989) that occur in women using oral contraceptives and

described in the communities of the developed countries would be different from those in African women. It is also true that the smaller-dose oral contraceptives that are now the norm are associated with a lower CVD risk than the formulations common in the 1970s and 1980s.

OTHER NEUROLOGICAL DISORDERS

Epilepsies

The prevalence ratios of epilepsy per 1,000 range from 5 to 42 in Sub-Saharan Africa, compared with 5 to 8 in developed countries (Feksi et al., 1991a,b Gerritts, 1983 Goudsmit et al., 1983 Jilek and Aall-jilek, 1970 Osuntokun, 1992 Osuntokun et al., 1987a Tekle-Haimanot, 1990). Data suggest that epilepsy has a higher prevalence in poor, deprived communities in Sub-Saharan Africa than in communities with improved socioeconomic status and adequate access to health care facilities (Osuntokun, 1992 Sorvon and Farmer, 1988). The high prevalence of epilepsy in Sub-Saharan Africa and other developing countries may stem from a high frequency of birth trauma and other forms of head trauma infective, including parasitic, diseases (such as cysticercosis and cerebral malaria) of the central nervous system febrile convulsions and encephalopathies complicating the childhood exanthematas. Immunization against the childhood infections appeared to protect against epilepsy (Ogunniyi et al., 1988).

In some cultures it is believed that epilepsy is incurable because it is a manifestation of some divine intervention hence many African epileptics do not seek modern treatment. Fortunately, drug treatment has proven as effective here as in the developed countries, regardless of whether anticonvulsant therapy was started early or late (Feksi et al., 1991b Ogunniyi and Osuntokun, 1991). In Africa as elsewhere, about 70 percent of epileptics properly treated in the first year of the occurrence of seizures can go on to be seizure-free. Low compliance with a drug regimen remains a significant problem, however, and appropriate drugs are often unavailable or are too costly to be affordable for the vast majority of patients. Community surveys indicate that many epileptics are not under any form of treatment because of widespread inadequacy of the health care system. In most African countries, epilepsy continues to incur considerable social disadvantage and to cause major disruption in the sufferers' lives.

With respect to epilepsy and gender, there is a male preponderance of black African epileptics seen in hospitals, with the exception of two reports from Uganda and South Africa that documented female preponderance in a small series of 83 (38 males and 45 females) and 50 (21 males and 29 females) patients, respectively. Evidence from three Nigerian community-based studies indicating an excess of female over male epileptics, however, support the possibility that the disorder may occur more frequently in females than males in the region (Longe and Osuntokun, 1989 Osuntokun et al., 1982b, 1987b).

Demyelinating Diseases

In Africans, as in Caucasians, disseminated myelitis with optic neuritis (neuromyelitis optica, Devic's disease) affects both sexes equally (Osuntokun, 1971a Spillane, 1973). Of the few anecdotal cases of multiple sclerosis reported in Africans, females are in slight excess (Collomb et al., 1970 Kanyerezi et al., 1980 Lisk, 1991 Tekle-Haimanot, 1985). Among Caucasians in most published series, males have been affected more often than females by multiple sclerosis, but the disease often begins earlier and runs a more rapid course in females (Acheson, 1972).

Neurologic Complications of Collagen Diseases

Collagen diseases appear to be relatively uncommon in black Africans, among whom the prevalence of autoimmune disorders is lower than in Caucasians polymyositis/dermatomyositis, whether idiopathic or secondary to an underlying neoplasm (which may be occult), is the third most common disease of muscles after pyomyositis and the muscular dystrophies in black Africans. As in Caucasians, females predominate among


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