Examples of treatments that slow the progress of neurological disease are numerous. A malignant cerebral glioma is almost universally fatal, but high-dose corticosteroids, neurosurgical debulking, radiotherapy, and chemotherapy may slow tumor growth and prolong survival (see Chapters 52E and 52F). The β-interferons, glatiramer, natalizumab, or mitoxantrone may reduce relapses and slow the progress of MS (see Chapter 54). Liver transplantation in familial amyloid polyneuropathy may slow or arrest disease progression (see Chapter 76). Riluzole may slow the progress of ALS (see Chapter 74). Despite many efforts to slow the progression of Parkinson disease (PD), no neuroprotective therapy has proved to be effective, although certain monoamine oxidase B inhibitors and dopamine agonists delay the onset of levodopa-related motor complications.

Symptomatic treatment is available for many neurological diseases. Relief of pain, although not curative, is the most important duty of the physician and can be accomplished in many ways (see Chapter 44). Baclofen and tizanidine can reduce spasticity, particularly in spinal cord disease, without affecting the disorder causing it. Injections of botulinum toxin provide marked relief in patients with dystonia, spasticity, and other disorders manifested by abnormal muscle contractions. High-dose corticosteroid therapy reduces the edema surrounding a brain tumor, temporarily relieving headache and neurological deficits without necessarily affecting tumor growth. In PD, dopaminergic drugs partly or completely relieve symptoms for a period, without affecting the progressive degeneration of substantia nigra neurons (see Chapter 71). The physician-patient relationship and the placebo response both are important tools used by the experienced neurologist in helping to relieve a patient’s symptoms.

Circumventing Functional Disability

In neurological diseases such as Alzheimer disease, PD, and ALS, the clinical course usually is progressive. Other disorders, such as stroke and spinal cord injury, have an acute onset, and the damage occurs before the neurologist first sees the patient. Although some recovery is expected, substantial functional deficits often persist. In both situations, many ways to circumvent the functional disability and the resultant handicap are available.

Neurological rehabilitation is the discipline that concentrates on restoration of function (see Chapter 48). Physical and occupational therapy help the patient to strengthen weak muscles, retrain the nervous system to compensate for lost function, increase mobility, and reduce spasticity. Some authorities believe that cognitive or behavioral therapy may similarly reeducate undamaged cortical areas to compensate for the effects of brain injury and stroke. Orthopedic procedures can be beneficial for rehabilitation; transfer of the tibialis posterior tendon to the dorsum of the foot can correct a footdrop in appropriate cases. Surgical release of Achilles tendon and iliotibial contractures in boys with Duchenne muscular dystrophy can delay the loss of ability to walk by 2 years or more.

Aids and appliances such as ankle-foot orthoses to prevent footdrop, canes, walkers, and wheelchairs can increase mobility and limit handicap. Changes to the home and work environment—a ramp or stair lift, widening of doors to allow wheelchair access, rails for the bath and toilet, replacement of the bath with a shower and shower chair—can be of great help to the patient. Only the ingenuity of clinicians and biomechanical engineers, the availability of technology, and the cost limit the scope of such appliances. Cochlear implants are already in clinical use for persons who were born deaf. Computer-controlled motorized body and lower-limb braces may allow paraplegic patients to walk.

The range of options available to help a patient with a severe, chronic neurological disease can be illustrated by reference to ALS. In the early stages, the patient may simply need enlarged handles on tools, pens, and utensils to compensate for a weak hand grip, or a cane to help with walking. Later, the patient may need a wheelchair and home adaptation. Speech therapy, a communication board, or a computer with specialized software can help when speech is severely impaired. Weight loss and choking from dysphagia may necessitate a percutaneous gastrostomy. An incentive spirometer and an artificial cough machine can protect respiratory function (see Respiratory Failure later in the chapter). If the patient decides not to use a ventilator, end-of-life counseling and hospice care are needed.

Management of disabilities in patients with progressive neurological diseases may tax the neurologist’s knowledge and ingenuity, but the beneficial effect of symptomatic therapy on patients and families makes the effort worthwhile and demonstrates that no neurological disease is untreatable. Collaboration with colleagues in other fields (e.g., pulmonary medicine, physical therapy, biomedical engineering, hospice care) often can be extremely helpful.

Principles of Symptom Management

Treatment of Common Neurological Symptoms

Several symptoms, such as pain, weakness, dysphagia, and respiratory failure, are common to many different neurological diseases. This section outlines the general principles that govern management of these symptoms. Chapters 44, 45, and 48 provide more complete discussions. Specific treatment for individual diseases is found in the relevant chapters in Volume II of this book.

Pain

The first step in pain management is to diagnose the source of the pain and assess the prognosis of the disease (see Chapter 44). Consider, for example, a patient with incapacitating pain in one leg from carcinoma infiltrating the lumbosacral plexus on one side. This patient’s life expectancy may be measured in weeks or months, and progressive plexus damage will produce leg paralysis. Destructive procedures and narcotics are justified in this situation. Surgical interruption of pain pathways is considered the final choice to relieve pain from carcinomatous infiltration of the lumbosacral plexus. Such procedures include surgical or chemical posterior rhizotomy, contralateral anterolateral spinothalamic tractotomy in the midthoracic region, and stereotactic contralateral thalamotomy. Tachyphylaxis for narcotics can occur, and the oral dose of narcotics required to control pain may rise rapidly in patients who live for several months. This does not appear to occur with morphine administered by an intrathecal or epidural spinal catheter using a subcutaneous infusion pump.

Narcotics should not be used for patients with nonmalignant chronic pain syndromes such as painful polyneuropathies or low back pain, because of the development of tachyphylaxis and the risk of producing drug dependency without pain control. Biofeedback, hypnosis, and acupuncture may help some patients control pain. Antidepressant drugs are of benefit in many chronic pain syndromes by blocking the neurochemical transmitter mechanisms of central nervous system pain pathways, as well as treating depression. Many patients are resistant to taking antidepressant drugs for pain because they insist that the pain is real and not from depression; the effectiveness of antidepressant drugs for pain control is a point that needs to be clarified in such instances. Sometimes a single drug may be effective, but frequently a combination of a selective serotonin reuptake inhibitor (SSRI) and a tricyclic antidepressant (TCA) is better.

Sensory Loss, Paresthesias, and Burning Pain

Occasionally, sensory loss produces an intolerable positive sensation termed anesthesia dolorosa that may respond to a combination of a TCA with either carbamazepine, gabapentin, pregabalin, or an SSRI. Paresthesias generally result from damage to the large-diameter myelinated axons in the peripheral nerves or posterior columns of the spinal cord. Patients who complain of burning sensations from small-fiber peripheral neuropathies often are helped by a TCA, an SSRI, or pregabalin, or a combination of these.

Weakness

The management of weakness, considered more fully in Chapter 48, is a major component of neurological rehabilitation. Choice of treatment depends on the extent, severity, and prognosis of the patient’s weakness. For example, weakness of flexion of the ankle due to Charcot-Marie-Tooth disease may be treated with a triple arthrodesis of the foot. Such a procedure, however, would not be appropriate to overcome the footdrop caused by a more rapidly progressive condition such as ALS. For such patients, an ankle-foot orthosis is best. Most neuromuscular conditions are benefited by exercise, although fatigue limits the amount of exercise that can be tolerated. Myasthenia gravis, however, is worsened by exercise. Weakness due to upper motor neuron disease can be addressed by physical and occupational therapy to promote the use of alternative neuronal pathways. Medications such as baclofen, tizanidine, and botulinum toxin injections reduce spasticity and may improve function in upper motor neuron disorders.

Respiratory Failure

Respiratory failure may develop in several neurological diseases (Box 43.2; see also Chapter 45). Patients with chronic neuromuscular diseases often complain of respiratory distress when they are close to respiratory failure. Patients with a weak diaphragm experience dyspnea when lying supine, because the abdominal contents prolapse into the chest, thereby lowering the patient’s vital capacity and tidal volume. A neurologist or a pulmonary specialist who is relatively inexperienced in neurological problems affecting respiration may underestimate the warning signs of potentially fatal respiratory failure. This is particularly true in myasthenia gravis and Guillain-Barré syndrome. Blood gas measurements do not change until late in the development of respiratory failure in chronic neuromuscular diseases. By the time evidence of hypoxia and hypercapnia appears in the blood, the patient may be bordering on acute respiratory collapse. Reduced vital capacity, patient distress, and a good knowledge of the disease are better ways of judging impending respiratory failure. A patient with Duchenne muscular dystrophy and a vital capacity of 600 mL may survive for several years without dyspnea. A patient with myasthenia gravis who has a vital capacity of 1200 mL but is anxious, sweating, and complaining of dyspnea is at serious risk for the development of fatal respiratory paralysis. With borderline respiratory function, sleep or sedation may produce carbon dioxide retention and narcosis, leading to further respiratory suppression and death.

Ethical Considerations in the Treatment of Respiratory Failure

Respiratory failure was once invariably fatal but now is commonly treated by noninvasive positive-pressure ventilation in the early stages and by intubation and positive-pressure ventilation in the terminal stages. The treatment of chronic progressive respiratory failure in neuromuscular diseases such as ALS and muscular dystrophy is very challenging. Moreover, cultural differences in different countries must be recognized. For example, in Japan, it is established practice to provide the ALS patient with a tracheostomy and positive-pressure ventilation when signs of early respiratory failure appear. In Western countries, most patients consider life on a ventilator unacceptable, and the neurologist must discuss quality-of-life issues with the patient and family before intubation.

Ideally, decisions about life-support measures should be made long before the patient is in acute respiratory distress, because it is more difficult to make these decisions when death is imminent. Patients and families require considerable counseling by the neurologist and may benefit from speaking to others who have experienced the situation, such as patients on a ventilator or persons who have lost a relative to ALS. Many patients cannot make a definitive decision about life-support measures and so defer the decision until the emergency occurs.

In these matters, the decision of a competent patient or the healthcare surrogate (in cases of an incompetent patient or one with whom communication is impossible) holds primacy. For instance, a 40-year-old patient with ALS may request respiratory support to see a child graduate or marry, even though no likelihood of recovery exists. On the other hand, a request to continue ventilator support for a 90-year-old patient with cancer and severe dementia cannot be considered rational, and the physician should convey the hopelessness of the situation and the patient’s unnecessary suffering to the next of kin. Patients who decide against ventilator support should provide a living will or terminal care document to their physician and next of kin and legally grant to a designated person (the healthcare surrogate) the power of attorney to make medical management decisions for them if they become incompetent. Even if patients have prepared a living will, they will be taken by emergency services to a hospital emergency department and be intubated unless proper arrangements are in place for end-of-life care at home, usually through hospice services.

For patients who decide to request ventilator support, health insurance and economic matters must be considered. Although the availability of insurance to cover the cost of ventilator care is paramount in the United States, in Japan the health insurance system pays for the costs of 24-hour home ventilatory care for all ALS patients.

Patients with a tracheostomy may still be able to talk using a valved tracheostomy tube or a partially inflated cuff, but many lose bulbar functions and need to use communication devices such as computers or letter boards. Many of the conditions listed in Table 43.2 also cause limb paralysis, which further impairs the ability to communicate. Quality of life usually becomes an issue when ventilator dependency becomes permanent. In many patients, the prognosis becomes clear within a relatively short time, as with stroke and coma. Because the patient is unconscious, the healthcare surrogate or, if such a person is not designated, the next of kin must decide, with the advice of the doctor, whether to continue respiratory support. If the healthcare surrogate or family of an unconscious patient requests that respiratory support be discontinued, it is standard medical practice in most parts of the world to do so. The legal and ethical issues are more complex with an awake and competent patient who requests that the ventilator be switched off. Although the legal systems in many parts of the world accept that such requests fall under the right of the patient to refuse medical treatment, involvement of a hospital ethics committee is strongly recommended.

Managing Terminal Respiratory Failure

If the patient opts for life-support measures, an elective tracheostomy and intermittent positive-pressure ventilation should be offered at the first signs of terminal respiratory failure. Patients who have respiratory insufficiency, whether or not they decide to opt for tracheostomy, often can be helped for a prolonged period by noninvasive positive-pressure ventilation through a nose mask or nasal “pillows.” Patients who decide against respiratory support should be counseled not to go to the hospital in a crisis, because they will inevitably be intubated. They should be referred to home hospice services, and when terminal respiratory distress appears, home treatment with oxygen, morphine, and sedation will be provided, despite the risk that this may hasten death. Neurologists should learn to manage chronic respiratory failure due to neurological disease. Although neurologists must work collaboratively with the intensive care specialist and hospice doctors, they should assume an active role in management decisions.

Memory Impairment and Dementia

Alzheimer disease is the most common cause of progressive impairment of memory and dementia, and only symptomatic care is possible, which includes anticholinesterase inhibitors. Some causes of progressive dementia are curable (see Chapter 66), and their recognition important. Even if no specific curative treatment is available, the experienced neurologist can provide essential advice to the family of a patient with a condition like Alzheimer disease on how to anticipate problems and minimize them. This includes helping the patient to make shopping lists and checklists of things to do before leaving the kitchen or the house and before going to bed. For a period, these measures can prevent the patient from leaving the house unlocked, or from forgetting about a pot boiling on the stove. Inevitably, the patient will have difficulty managing a checkbook, and a family member should take over money management before financial disaster occurs. The patient eventually will need either a live-in companion or must move in with a family member or into a nursing home. Much of the neurologist’s efforts are directed toward helping the patient and family circumvent problems and adjust to expected changes. Family members need access to books and publications by foundations and support groups such as the Alzheimer’s Disease Association.

Treatment of Secondary Effects of Neurological Disease

Predictable reactions occur in a patient who is given the diagnosis of a chronic incurable neurological disease. These reactions progress at variable rates through the stages of anger, denial, “why me?,” depression, and eventually acceptance, often with oscillation among these phases. The neurologist must provide support through this process of adjustment, sometimes with the assistance of a mental health professional.

The psychological, social, and economic impact of the disease on the family also must be considered. Family members caring for a patient with Alzheimer disease often say that it is like looking after a young child but with much more stress. The family of a boy with Duchenne muscular dystrophy will experience both mental and physical stress because the child eventually will lose the ability to walk and must be lifted into and out of chairs, bed, and bath. Mechanical lifting devices can help, but they are slow and clumsy. Often, home alterations are needed to allow one-level living and wheelchair access. Someone needs to get up several times a night to turn the patient in bed. Lack of sleep and increasing daytime care strain the family dynamics. Other children may be neglected and emotionally deprived; marital disharmony is common. The physician may need to refer such families for counseling or put them in touch with a family support group. School authorities need information and should be encouraged to keep the child in mainstream schooling. As the young man with Duchenne muscular dystrophy reaches maturity, he may consider college or employment, and the neurologist can provide information to assist the relevant authorities.

The neurologist caring for a patient with a progressive neurological disease plays an important role for both the patient and the family. Help from many other professionals often is required, but the neurologist must anchor the management team.

Explaining the Prognosis

Establishing the diagnosis is necessary for the neurologist to be able to define the prognosis for the patient and family. The physician should ascertain what the patient and family want to know and then provide answers at a rate they can accept. Some patients fear that they will die or become a “vegetable” within a few months and are greatly relieved to learn that they have several years of useful life ahead. Patients may wish to make financial arrangements or accelerate unfulfilled plans if the prognosis is poor. Patients may not always wish to be told the prognosis, but relatives generally want to know. The neurologist should always present the prognosis with some hopeful caveats, because the diagnosis may be wrong or the disease may not follow the expected course. Patients should always be given some hope; even ALS can arrest or remit. A useful way to cushion bad news is to say that the patient needs to hope for the best but plan for the worst.

Palliation and Care of the Terminally Ill Patient

Palliative care starts from the earliest stage of the doctor-patient relationship. Pain, depression, and anxiety are the three major symptoms that require palliation. The treatment of pain is considered in Chapter 44. Psychological reactions are treated with a range of pharmacological agents, including benzodiazepines for anxiety, neuroleptics for psychotic symptoms, and an ever-increasing list of medications for depression. The psychological support for the patient and family provided by the doctor, however, usually is more important than pharmacological therapy. The experienced neurologist provides help to the patient and family by drawing on lessons learned from treating many similar patients. Even though the disease and its effects cannot be arrested, the neurologist can help ease the emotional burden. When possible, the neurologist should discuss each new phase of the disease with the patient and family before it occurs. No patient likes to hear of impending deterioration, but if the neurologist clarifies the importance of anticipation, the patient is reassured that the doctor is ready to deal with change, when and if it occurs.

Genetic Counseling

Approximately 1 in 10 neurological conditions has a genetic basis. Rapid advances in molecular genetics require that the neurologist keep abreast of the many diseases that can be diagnosed by genetic testing (see Chapter 40). Genetic counseling should take into account the limitations and pitfalls of the various commercially available DNA tests, however, and the assistance of an experienced medical geneticist is invaluable. A parent with a neurological disease commonly fears that the disease will pass to the children. Hence, if a disease has no hereditary component, the parent should be reassured. If the disease has a hereditary tendency, the risk to offspring must be discussed. For instance, the chance of occurrence of MS in the offspring of a patient with MS is higher than that in the general population, but it is still only about 3%.

In Huntington disease (HD), however, the risk that each offspring will inherit the disease is 50%; at-risk persons may choose not to have children because of this. An offspring of a patient with HD can be advised about alternative ways to have a family—adoption, artificial insemination by donor when the husband is at risk, or surrogate gamete in vitro fertilization when the wife is at risk. In addition, an individual carrying a mutant gene who wishes to have a child can use the technique of embryo genotesting. After in vitro fertilization with the parents’ ova and sperm, the embryo is allowed to grow to the 8- to 16-cell stage. A single cell is then removed for DNA testing; embryos bearing two normal huntingtin genes are accepted for implantation, and those with an abnormal huntingtin gene are discarded. Cost and availability of services limit the use of this procedure.

The neurologist should provide the patient and spouse with the available information about the mode of inheritance of the disease and, when relevant, the possibilities for prenatal and preclinical diagnosis. A couple’s attitude to therapeutic termination of pregnancy should be part of the discussion. When a disease has an autosomal recessive mode of inheritance and the gene frequency in the population is low, children of an affected parent are at very little risk unless the patient marries a close relative. If the gene frequency in the general population is known, the risk of having an affected child can be quantified.

Each pregnancy of a parent with a fully penetrant autosomal dominant disorder has a 50% risk of resulting in an offspring bearing the mutant gene. If the proband is apparently a sporadic case, a risk approaching 50% must still be assigned because many apparently sporadic cases are in fact due to dominantly inherited mutations in which the proband was the product of undisclosed parentage or are due to new mutations.

In response to genetic counseling, some patients may make what the neurologist considers to be an irrational decision about having children. Some patients consider 50% quite good odds even when considering the risk of having a child with HD. On the other hand, some patients may decide against having children because of odds of 1 in 100. In both circumstances, the physician should provide as much information as possible about the meaning of the results of the genetic tests but must emphasize that the ultimate decision rests with the couple.

Genetic testing can reveal that an asymptomatic person will almost certainly develop the disorder. Asymptomatic patients who carry the mutation for the disease can be identified by the use of testing for the mutant gene. Huntington disease and myotonic dystrophy are two such examples. Because HD currently is not treatable and affected persons have a high suicide rate, the neurologist should be aware of the risks that accompany disclosure. The services of a qualified genetic counselor are very helpful for managing these problems. Before testing is begun, the genetic counselor will thoroughly review the hypothetical possibilities and potential management decisions with the patient and spouse. Although most people think they want to know their genetic status, after considering the implications, many conclude that a positive result on genetic testing would be too difficult to tolerate and, hence, forgo screening.