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Neurological Problems

Confusion | seizures | motor & sensory deficits (including pain) | increased intracranial pressure | spinal cord compression | other (update 1/12/2005)

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The neurological problems most common in terminal illness include confusion, seizures, motor and/or sensory changes (including pain), decreased consciousness, coma, and/or spinal cord compression. The causes of neurological problems, especially those involving confusion or other changes in consciousness are often complex and interrelated. In patients with cancer, causes of neurological problems include central nervous system (CNS) metastases or primary tumors of the CNS; non-metastatic processes such as side effects of treatment (especially radiation), infections, metabolic disorders, distant effects of cancer (paraneoplastic syndromes or PNSs), increased intracranial pressure, and spinal cord compression. Primary neurological disease such as Parkinson's, etc. may also affect patients with cancer. In patients with AIDS, neurological problems are commonly due to AIDS dementia complex and opportunistic infections such as cytomegalovirus, cryptococcal meningitis, and toxoplasmic encephalitis. Painful peripheral neuropathy is common in AIDS and the specific cause is not always identifiable.

A change in neurological status, whether cognitive, motor, or sensory is often an important sign of disease progression and potentially serious complications in cancer and AIDS. The rapid onset of a problem is nearly always more serious than a gradual onset. Neurological progression and/or complication is invariably more amenable to curative or palliative treatment in early stages. Therefore, all persons involved (nurse, doctor, patient, and family) should be alert to neurological problems and communicate the presence or suspicion of a problem at the earliest sign of neurological deficit.

Quick Neurological Assessment Flow of speech Orientation Memory (especially short-term) Thought processes Attention span Ability to follow commands Visual acuity CNs III (oculomotor), IV (trochlear - downward, inward eye movement), V (trigeminal - motor/jaw; sensory), VI (abducens - lateral eye movement), VII (facial - facial expression; taste, saliva, tears) Fine motor movements Upper and lower extremity coordination, including gait

Confusion: Delirium and Dementia

It is important to understand the differences between delirium and dementia because one (delirium) is sometimes reversible, and the other (dementia) seldom, if ever, reversible. There are situations, such as Alzheimer's disease, in which a person may experience both delirium and dementia.

Delirium is an acute state of confusion with a relatively rapid onset, and includes some degree of disorientation, inability to maintain attention, agitation or lethargy, and illusions or hallucinations. Disorientation may be to person, place, time, or all three. Clinical subtypes of delerium include hyperactive, hypoactive, and mixed. Mental status may change from hour to hour and symptoms worsen at night ("sundowning"). Some people deny any problem, and mood changes may be the primary outward manifestation of delirium. Common causes of delirium are listed below. Often there is more than one etiology. Common etiologies of delerium in advanced cancer include:

• Treatment: Opioids, steroids, phenothiazines, sedatives, radiation (to brain).
• Primary disease: Brain metastases, primary tumor growth, increased intracranial pressure.
• Distant effects of primary disease: Paraneoplastic syndromes, electrolyte imbalance (e.g. hypercalcemia or high blood calcium level, hyponatremia or low blood sodium level, hypoglycemia or low blood glucose level); and CNS paraneoplastic syndromes (especially with lung, breast, and ovarian cancer); organ failure, including liver, kidney, lung, thyroid, adrenals.
• Other symptoms/problems: Pain, anemia, dyspnea, fecal impaction, urine retention; nutritional deficiencies, e.g., cachexia (irreversible metabolic starvation), vitamin B12 deficiency; infection (and sometimes antibiotics taken for infection).
• Other causes: Nonmalignant disease (Alzheimer's disease, atherosclerosis, AIDS dementia), chronic isolation, and psychiatric disorder (especially depression and mania).

Dementia is a chronic condition characterized by gradual decrease in mental faculties often beginning with slight memory losses, difficulty concentrating, or other deficits either unrecognized or excused by the patient and others. Recognizing that their mental abilities are diminishing, some people will gradually restrict their activities and scope of life to compensate for the losses. Often the only early manifestation of dementia is quietness and somewhat depressed mood. At least in the early stages of dementia, the person undergoing the loss of abilities is aware of the losses and often able to cover up at least some of the losses with confabulation, changing the subject, and the like. People with dementia are predisposed to episodes of delirium except in the last stages of progressive dementia such as in Alzheimer's disease.

Managing Confusion

As with other problems of advanced disease, early identification and treatment of (at least) delerium minimizes impact and disability. Failure to identify delerium early in the process may result in long-term disability. In addition, confusional states may signal disease advance, and thus the need to reconsider therapy or therapy goals.

Whenever possible, the cause is treated and resolved, i.e., the pain managed, impaction removed, tumor edema reduced, and so on. Unfortunately, it is not always possible to effectively address the cause, either because the cause is irreversible, such as in Alzheimer's disease; or because the confusion is part of the dying process, such as hypercalcemia in a person who is imminently terminal. The person's need for help in orientation is mediated by his or her condition. In other words, a person who is close to death usually does not need to know what year it is; but does usually need to know what procedure is about to be carried out or who is in the room. Symptomatic treatment of confusion includes:

• Antipsychotic medications, especially haloperidol (Haldol) decrease confusion and/or thought disorders and agitation.
• The person's environment should be as familiar as possible and be well-lighted, but not overly bright. There should be a night light, and if the person is able to walk, the bathroom should have a night light as well.
• The atmosphere should be calm and sensory overload should be avoided, especially in the evenings or at night when many people with confusion are less able to manage over-stimulation.
• Caregivers should explain in a brief, clear manner what they are doing or what is happening around the person who is confused. It is often necessary to repeat explanations. The person may need frequent reminders of person (who is visiting , giving care, etc.), place (where the person is), and time (including year).
• A clock and calendar should be present.
• Some patients are calmed by television and some are not.
• Staff changes should be avoided, and regular visits by family and friends encouraged.
• As much and as long as possible, activities of daily living should be carried out, including dressing and grooming daily.
• Safety, especially for people able to get out of bed, is always a concern. Physical restraints usually cause more agitation and problems than they alleviate. Wandering is best prevented or addressed by careful monitoring.

The value of a structured schedule cannot be overemphasized in minimizing confusion and caregiver fatigue. For example, allowing a patient to sleep during the day always results in difficulty sleeping at night as well as increased nighttime confusion. Structure is increased by writing out a schedule for the patient and caregivers.

Caring for a loved one who is confused is extraordinarily difficult emotionally, physically, and even spiritually. Readers are referred to the section on family for discussion of common issues and planning care.

Seizures

Although seizures are relatively uncommon in most terminal illness, any patient with primary or metastatic intracranial tumor(s) or related progressive disease is at risk for seizures; except that seizures are common in patients with slow-growing intracranial tumors and patients with cerebral metastases from melanoma. People with terminal illness and preexisting epilepsy, whether well-controlled or not, are at risk for seizures and/or untoward or toxic effects of medications. Factors that can precipitate seizures in a patient with intracranial tumors or epilepsy include noncompliance with taking anticonvulsant medications, sleep deprivation, excess alcohol, severe anxiety, dehydration, menses, and some medications, including tricyclic antidepressants. Seizures may also indicate disease progression or recurrance.

There are two basic types of seizures, partial and primary generalized, and within these, a variety of seizure types, ranging from simple seizures in which consciousness is maintained to grand mal seizures. The basic types of seizures are:

• Simple partial seizures may include convulsive jerking, difficulty speaking, sensory changes such as perception of flashing lights, emotional changes, or other symptoms.
• Complex partial seizures are characterized by changes in consciousness, often preceded by signs noted above.
• Absence (petit mal) seizures are characterized by impaired consciousness and sometimes include muscle jerking. Absence seizures are more common as a childhood disorder than in cancer.
• Myoclonic seizures are characterized by single or multiple muscle jerking.
• Tonic-clonic (grand mal) seizures last for one to three minutes and includes loss of consciousness, stiffening of the body, and jerking of arms and legs. The person may become cyanotic, drool, bite his or her tongue, and pass urine and/or stool. In most cases, the seizure ceases and except for being sore and tired, the person suffers no ill effects from the seizure itself (injury may occur, however).
• Rarely, seizures will be long-lasting or occur in a series lasting more than five minutes called status epilepticus, which is a life-threatening neurooncological emergency.

Managing Seizures

While a grand mal seizure is occurring, there is little a caregiver can do other than to protect, but not restrain, the person having the seizure. If standing, the person should be eased to the floor; or if in bed, kept from falling out. If there is warning, a soft cloth can be placed between the person's teeth (taking care to avoid being bitten), but the jaws should not be forced open. If the person is on the floor, a pad can be placed under the head to help prevent injury. As the person relaxes from the seizure his or her head should be turned to the side so that secretions can drain out rather than to lungs. Professional staff should be notified of the seizure, but it is unnecessary to call an ambulance unless the seizure is prolonged or injury occurs.

Seizures are managed or prevented with a variety of medications according to seizure type and response to medications. The most commonly used medication for prevention and/or treatment of seizures in patients with cancer is phenytoin (Dilantin) 300-400 mg/24 hours. Other medications include phenobarbital, carabmazapine (Tegratol), valproic acid (Depakene), gabapentin (Neurotonin), and others taken singly or sometimes in combination. If taking corticosteroids, the dose of corticosteroids may need to be increased.

Management of status epilepticus includes assurance of the airway, electrolyte screen, IV glucose (before electrolyte results), and IV benzodiazepine followed by IV phenytoin or valproate sodium.

Motor and Sensory Deficits

Motor and sensory deficits include difficulty walking, grasping, or related difficulties, including weakness; and/or tremors, numbness and tingling, or neuropathic or muscle pain in extremities. Falls, attributed to stumbling over some object, may actually be due to a neurological deficit. There are a number of causes of motor and sensory deficits in cancer, including tumor growth, paraneoplastic syndromes, metabolic disorders, treatment, and infections. In AIDS, causes include HIV infection, opportunistic infection (especially cytomegalovirus [CMV] or herpes), medications, or from unknown causes. Increased intracranial pressure and spinal cord compression are very important causes of motor and sensory deficits - some permanent or lethal, and are discussed below.

Managing Motor or Sensory Deficits

Motor and/or sensory deficits are treated according to cause. Pain is treated as discussed in the section on pain and pain management (see neuropathic pain). Typically, neuropathic pain is treated with a combination of opioid and tricyclic antidepressant or antiseizure medication. Mobility and independence are maintained as much and as long as possible. Referrals to occupational and/or physical therapy should be considered if life expectancy is not limited.

Increased intracranial pressure

Increased intracranial pressure (ICP) in terminal cancer is usually caused by metastasis to the brain or the covering of the brain (dura or meninges), or from edema (swelling) which is also usually caused by tumor. Although not all people with brain metastasis experience significant increased intracranial pressure, the risk is present in any person with brain metastasis, especially when the tumor grows rapidly.

Symptoms and signs of increased intracranial pressure may initially be subtle and include change in cosciousness (usually increasing somnolence), change in mental status, and restlessness. The classic triad of increased ICP includes:

• Papilledema (often with visual changes)
• Vomiting
• Headache (usually progressive and often most severe in early morning, sometimes awakening the patient. Headache varies in site and accompanying symptoms according to the site of the lesion(s).

Other signs of increased intracranial pressure include other mental changes, visual changes, seizures, paresis or weakness (on one or both sides of the body), nausea and vomiting, bowel and bladder dysfunction, and other neurological signs.

Managing Increased Intracranial Pressure

Severe or rapidly progressive increased intracranial pressure is an oncology emergency and thus requires immediate treatment. Treatment of increased intracranial pressure is directed to (1) reducing pressure, (2) palliating associated symptoms.

• Under ideal circumstances, surgery plus radiation is used to reduce pressure. Often, radiation and medication is the only option. Combined treatment usually gives longer survival rates than radiation alone, but is not appropriate for patients with disseminated metastases, which is about half of all patients with increased intracranial pressure. Corticosteroids provide quicker short-term relief than radiation; while radiation provides longer-term relief. Other medications and treatment modalities, including chemotherapy are used in limited numbers of cases.
• Nausea and vomiting are treated with anti-emetics.
• Activities that increase intracranial pressure include suctioning, turning, Valsalva's maneuver or straining (e.g., to have a bowel movement), hip flexion, and lying flat, prone, or with the head lower than the rest of the body. Activities that must take place should be spaced to give rest time between. Constipation must be prevented, and hypertension and fever controlled. Fluids are sometimes restricted. Alert, cooperative people can be turned passively. The person's head must be kept elevated. Extra attention must be paid to safety if confusion or seizures are a problem. For example, the bed should be kept at its lowest or closest to the floor setting, environmental hazards reduced, and the patient not left alone for any longer than is absolutely necessary.
• Confusion and other neurological deficits are addressed as discussed earlier.
• Pain is best managed with steroids and treatments discussed above. An opioid plus a phenothiazine, e.g., Haldol can be used if these measures are ineffective.

Spinal Cord Compression

Spinal cord compression (SCC) is an oncology emergency and requires immediate attention. Unless arrested, compression of the spinal cord causes paralysis (usually of the lower extremities), paraplegia, incontinence, constipation, pain, and high risk for skin breakdown. Thus significant deterioration in quality of life occurs. In most cases, spinal cord compression is due to vertebral metastasis, which, in turn results in pressure or traction on the spinal cord. The spine is a common site of metastasis (despite poor blood supply to the vertebrae) because of a large capillary capacity in the vertebrae and anatomical microstructures in which tumor products and micrometastases tend to accumulate.

While any cancer metastasized to the spine can cause spinal cord compression, the tumors most commonly associated with cord compression are lung, breast, prostate, and lymphoma.

Back pain is usually the first symptom of spinal cord compression. The pain is most commonly progressive, constant, dull, aching, and sometimes radiating. Pain may increase or progress slowly or at a rapid rate - with rapid progression more likely to result in lasting disability. The pain is usually exacerbated by movement (especially flexing the neck or raising the legs), coughing, sneezing, or straining; and not relieved by lying down, and sometimes relieved by sitting up.

Neurological deficits are usually the second major manifestation of spinal cord compression, but may begin after more than a month of back pain. Neurological deficits may have rapid onset and are most often motor disabilities, especially weakness of the lower extremities. In early stages, neurological deficits such as weakness, dizziness, stumbling, or even falls may not appear to be significant to the patient. Urine retention, manifested by frequent, small voiding, is relatively common. Other neurological deficits that occur with less frequency include bowel dysfunction, sexual impotence, and numbness and tingling of lower extremities.

Managing Spinal Cord Compression

Spinal cord compression is an oncology emergency and thus requires quick treatment to avoid lasting disability. Treatment in early stages is usually effective. If neurological deficits are allowed to progress, they generally become permanent and significant disability occurs. Rapid onset of symptoms presents a poorer prognosis than slow onset. Treatment includes:

• Radiation therapy, combined with steroid therapy (dexamethasone) is the standard treatment for spinal cord compression in most patients, even when cord compression has not definitely occurred.
• Surgery (laminectomy) carries greater risks and is more invasive. Laminectomy may be indicated when there is bone deformity, inability to receive further radiation, high cervical (in the neck) compression, and radiation-resistant tumor
• Chemotherapy is occasionally used.

Other Neurological Problems

Although rare, neurological paraneoplastic syndromes (PNS) can cause a variety of (often severe) cognitive, sensory, and motor deficits. While the specific cause(s) of PNSs are not known, it is likely that they are immune-mediated. Small cell carcinoma of the lung is most commonly associated with neurological (and other) PNSs. Unlike most other complications of cancer, neurological PNSs tend to occur early rather than late in the course of the illness and thus may be the first sign of disease. Neurological PNSs include:

• Paraneoplastic cerebellar degeneration: global loss of function.
• Paraneoplastic sensory neuropathy/encephalomelitis: pain, loss of proprioception, other disabilities.
• Lambert-Eaton myasthenic syndrome: loss of motor, but not sensory function.
• Retinopathy or optic neuritis.
• Limbic encephalitis: progressive and profound cognitive and other neurological impairment.

Treatment of neurological PNSs is unsatisfactory, though treatment of other PNSs such as syndrome of inappropriate antidiuretic hormone (SIADH) and hypercalcemia is often effective.

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