Patients with neurologic disease
Several neurologic disorders follow a degenerative course that eventually results in the patient’s death. These disorders impact quality of life for both patients and families, in some cases for decades. These disorders present a challenge to health care providers seeking to both manage the symptoms and determine an appropriate time to refer the patient to a palliative care team and, later, to a hospice program. Although determining a realistic six-month prognosis is difficult, it’s possible to ease the patient’s symptoms and support the patient’s family as these diseases reach their final stages.
This chapter reviews three terminal neurologic disorders: amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Huntington’s disease.
Amyotrophic lateral sclerosis
ALS is a progressive, degenerative disease. It’s also known as Lou Gehrig’s disease, after the popular New York Yankee baseball player who was diagnosed with it. ALS is the most common motor neuron disease in the United States, with about 5,000 new cases diagnosed each year. It’s more common in men and usually is diagnosed between ages 40 and 60. About half of those who develop ALS die within 2 to 5 years after symptoms start, usually from respiratory failure. (See Theories about amyotrophic lateral sclerosis, page 142.)
Progressive symptoms
Symptoms of ALS result from the degeneration and demyelination of motor neurons in the anterior horn of the spinal cord, brain stem, and cerebral cortex.
Upper motor neuron dysfunction causes spastic, weak muscles with fasciculations and increased deep tendon reflexes. Lower motor neuron dysfunction causes muscle flaccidity, paresis, paralysis, and atrophy. Death of the motor neurons results in axonal degeneration, demyelination, glial proliferation, and scarring along the corticospinal tract.
Upper motor neuron dysfunction causes spastic, weak muscles with fasciculations and increased deep tendon reflexes. Lower motor neuron dysfunction causes muscle flaccidity, paresis, paralysis, and atrophy. Death of the motor neurons results in axonal degeneration, demyelination, glial proliferation, and scarring along the corticospinal tract.
Theories about amyotrophic lateral sclerosis
We don’t know a great deal about what causes amyotrophic lateral sclerosis (ALS) or what makes it progress. Here are some theories.
The disease may have a genetic component. Familial ALS, linked to chromosome 21 defects, makes up about 5%to 10%of cases. The rest are known as the sporadic form and include no family history.
ALS also may have metabolic or viral roots. Abnormal glutamate metabolism and hydrogen peroxide production may be involved. And echovirus RNA has been isolated in spinal cord tissue in some people with the nonfamilial form.
ALS also has been linked to oxidative stress and cellular damage —as have Alzheimer’s disease and Parkinson’s disease. Neurons are easily damaged by oxygen-free radicals and the activation of immune cells that propagate further cellular injury.
Other variables include environmental influences, excess intracellular calcium, and antibodies to calcium channels.
Initially, ALS causes weakness and paresis that may affect only one muscle group. Early in the disease, surviving motor neurons sprout new branches to affected muscle fibers, which preserves muscle strength. However, when more than half of lower motor neurons are affected, this process fails, and weakness becomes detectable. It typically affects the hands first, then the upper arms and shoulders, and finally the legs. Continued brainstem involvement leads to progressive atrophy of the tongue and facial muscles and eventually to dysphagia and dysarthria. As the frontal lobe becomes involved, emotional lability and loss of control may result, but vision, hearing, sensation, and cognitive ability usually remain intact.
Diagnosis and treatment
ALS is a diagnosis of exclusion based on the patient’s signs and symptoms. Electromyography, nerve conduction studies, magnetic resonance imaging, and blood testing may be used to rule out other disorders, such as multiple
sclerosis, brain and spinal cord tumors, infection by human immunodeficiency virus, and Lyme disease.
sclerosis, brain and spinal cord tumors, infection by human immunodeficiency virus, and Lyme disease.
Riluzole (Rilutek), a glutamate inhibitor, is the only drug currently used for ALS. It doesn’t cure the disease but may prolong life for several months and delay the need for mechanical ventilation.
Patients with ALS benefit from multidisciplinary care that seeks to prevent the complications of immobility and to address the physical and psychological needs of patient and family.
Alzheimer’s disease
Alzheimer’s disease is a form of dementia marked by progressive deterioration of intellectual function, emotional control, social behavior, and motivation. The progression rate varies, but eventually the patient will be unable to make judgments and care for himself. Patients may live many years with the disorder, but the average time from diagnosis to death is 8 years.
Alzheimer’s disease is the most common degenerative neurologic illness and the most common cause of cognitive impairment in adults; it currently affects more than 4 million people in the United States. (See Theories about Alzheimer’s disease, page 144.) Early-onset Alzheimer’s disease, which is rare, can affect adults ages 30 to 60. Usually, however, the disease affects people older than age 60.
Brain changes
After the patient’s death, characteristic autopsy findings include loss of nerve cells and the presence of neurofibrillary tangles and amyloid plaques in the brain. These tangles and plaques disrupt transmission of nerve impulses and communication between neurons. Consequently, blood flow to affected brain areas decreases, and the brain atrophies. As the disease progresses, more brain areas are affected, with added symptoms corresponding to the affected areas. (See Staging Alzheimer’s disease, pages 145 and 146.)
Several structural and chemical changes occur in the brain, especially in the hippocampus and the frontal and temporal lobes of the cerebral cortex. As neurons in the hippocampus and related structures are destroyed, short-term memory fails, and the patient’s ability to perform familiar tasks declines. As neurons in the cerebral cortex are destroyed, the patient loses language skills and judgment, and emotions become increasingly labile. Eventually, the person becomes completely dependent and unresponsive.
Theories about Alzheimer’s disease
No one knows what causes Alzheimer’s disease or much about what raises the risk of developing it. Here are some theories.
Risk factors
The main risk factors for Alzheimer’s disease seem to be age, family history, and the presence of the apolipoprotein E (apoE) allele on chromosome 19.
The likelihood of being diagnosed with Alzheimer’s disease doubles for every 5 years of age beyond age 65.
People who have a first-degree relative diagnosed with Alzheimer’s disease face a fourfold increase in the risk of developing the disease. This risk is even greater if the disease shows up in more than one generation.
ApoE is a protein that appears on the surface of cholesterol molecules and helps carry cholesterol throughout the body. It’s also found in neurons of healthy brains and in amyloid plaques and neurofibrillary tangles. Carriers of the ApoE allele have have an increased risk of Alzheimer’s disease; those with two copies of the gene have an even greater risk. However, this genetic pattern also occurs in people without Alzheimer’s disease.
Other risk factors for Alzheimer’s disease (and other dementias) include cerebral damage, hypertension, peripheral vascular disease, less education, and a history of traumatic brain injury.
Causes
Causes of Alzheimer’s disease may include:
loss of neurotransmitter stimulation by choline acetyltransferase
a mutation for encoding an amyloid precursor protein
an alteration in apolipoprotein E
gene defects on chromosomes 14, 19, or 21 that promote clumping and precipitation of insoluble amyloid as plaques in the brain.
Disease stages
Alzheimer’s disease has been classified in multiple ways, with some using a simple three-point scale and others listing up to seven stages based on symptoms and performance. However it’s classified, Alzheimer’s disease invariably leads to the patient’s death and the need for palliative care.
Staging Alzheimer’s disease
Although there’s no standardized system for staging Alzheimer’s disease, you can use these general categories.
| Stage | Characteristics |
|---|---|
| Mild |
|
| Moderate |
|
| Moderately severe |
|
| Severe |
|
| End-stage |
|
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