Chapter 6 Neurologic Disorders (2024)

KEY TERMS AND DEFINITIONS

LEARNING OBJECTIVES

After completing this chapter, you should be able to

1. Describe how lesions in the brain and peripheral nervous system are related to neurological diseases.

2. List the causes, symptoms, and expected course of the following illnesses:

   • Headache—migraine, cluster, and tension.

   • Stroke.

   • Parkinson’s disease.

   • Dementia.

   • Epilepsy.

   • Multiple sclerosis.

   • Neuropathic pain.

   • Sleep disorders.

3. Describe the psychosocial consequences for patients and families of patients with neurologic disorders.

4. State the generic and brand names of representative medications used to treat neurologic disorders, along with dosage forms and available doses.

5. List the mechanism of action, common adverse effects, and special precautions of medications used to treat neurologic disorders.

Neurologic disorders tend to be chronic illnesses, many of which are progressive in the decline of function. They include conditions ranging from those as common as migraine headaches to rare genetic diseases. Some diseases affect memory and reasoning, such as Alzheimer’s disease. Others, such as multiple sclerosis and amyotrophic lateral sclerosis, cause deterioration in the body while the mind is mostly intact. And many, such as epilepsy, are subject to social stigma, due to the sudden and often frightening onset of seizures or the muscle rigidity and hallucinations associated with Parkinson’s disease. Many of these conditions cause stress not only for the patient but also for caregivers and loved ones. Occasionally, medications can cause neurologic deficits.

In the past 30 years, there has been an enormous increase in the availability of medications to treat many of these diseases but none to cure them. Many of the medications in use are prescribed to delay disease progression; others are indicated to help manage the symptoms. People with neurologic diseases may have life spans close to normal but with 20 years or more of progressing disability. Patients and their families need health workers who understand the difficulties posed by their conditions.

What causes neurologic disorders? As the name implies, there are problems within the nervous system—the brain, spinal cord, and peripheral nerves that communicate with every part of the body. When this system is working well, we can multiply, remember old songs, walk a balance beam, hit a target with an arrow, and carry on a normal conversation. Our chewing and swallowing are coordinated so that we don’t choke. Our bowels and bladders do their jobs without stubbornly balking at their tasks. Our fingers can feel hot and cold objects, and we can feel a pebble in our shoe. We can pick up a quarter from the floor without falling over. We readily fall asleep when we are tired at night and wake up rested in the morning. Any of these systems can be thrown off by disease. Sometimes the disease attacks the nerves themselves. Sometimes there is a particular area of the brain that is affected. Often particular neurotransmitters—chemicals that carry messages from one nerve to another—are out of balance.

Many of the medications used to treat neurologic disorders are specific to a certain disease. Others are prescribed for several different conditions. Some medications used to treat epilepsy are also used to treat pain conditions, migraine headaches, and mood disorders. Some medications used to treat depression are also used to treat pain and migraine. There are many overlapping characteristics of neurologic diseases and psychiatric diseases (Chapter 7). Neurologic disorders are more likely to be detected by a physical examination and diagnostic procedures, such as MRI (magnetic resonance imaging) scans and EEGs (electroencephalograms). Psychiatric diseases are more likely to be diagnosed by the patients’ descriptions of their emotions, thoughts, and behavior. There is often overlap—patients with neurologic disorders frequently experience depression, for example.

HEADACHE

Headache disorders are one of the most common neurologic conditions we encounter. Many conditions can cause headaches, and we must not treat this condition lightly. In addition, the overuse of over-the-counter (OTC) headache medications can lead to a condition of chronic daily headache, which is difficult to manage. Patients who describe frequent headaches, headaches that accompany certain activities (for example, coughing or sex), or a new headache that is the worst they have ever had, should see a doctor for evaluation. See Medication Table 6-1 for a list of medications commonly prescribed for the treatment of headache. (Medication Tables are located at the end of the chapter.)

For occasional tension headaches, OTC acetaminophen, ibuprofen, or naproxen is usually sufficient. (These medications are covered in detail in other chapters; please consult the index.) The patient can also be questioned about caffeine use. Sudden withdrawal from a daily high intake of caffeine can cause severe headaches, which can be treated by reintroducing a source of caffeine and gradually decreasing the amount ingested over several days.

Migraine headaches are a particularly distressing and incapacitating type of headache that is very common and may even occur in children. Migraines are characterized by throbbing on one side of the head. Patients are sensitive to light, sound, or both. Migraines are also known as “sick headaches” because they are frequently accompanied by nausea. In some patients the headache is preceded by a visual aura. Migraines are often relieved by sleep.

Many migraine sufferers are able to detect headache triggers by charting their headaches on a calendar. They can monitor how often the headaches occur, their intensity, and if a food or beverage appeared to cause the headache. Women often find that their headaches are more likely to occur at a certain time during their menstrual cycle. As with patients with tension headaches, patients with frequent migraine headaches should be encouraged to see a doctor to help better manage the problem. Infrequent migraines often will respond to OTC pain medications and rest, but more frequent migraines are better treated with medicines that prevent or reduce the frequency of the headaches, as well as medications that are used to stop the headache once it has started.

Cluster headaches are less common than migraine but also very debilitating when they occur. Unlike migraines, which are more common in women, cluster headaches are much more likely to occur in men. The headache is a short but intensely painful sensation. Cluster headache sufferers often describe the pain as feeling as if they had a knife stabbing one eyeball. In addition to intense pain on one side of the head, they often have a reddened, teary eye and runny nose. Cluster headache sufferers are not usually sensitive to light or sound. The headache is not relieved by sleep—in fact, the headache sometimes starts while the patient is asleep. Sometimes the patient will pace around or go outside if the weather is cold in an attempt to get some relief. This kind of headache usually only lasts a few minutes, but the patient experiences clusters of these short headaches—several in a day or over a few weeks—and then they will disappear for an extended period.

Because cluster headaches are very short in duration, oral medications are not useful since they take too long to work. For quick relief, injectable sumatriptan is used. Inhaled oxygen will abort an attack for some people. The strategy is also to prevent the attacks by using medications prophylactically, although not all of the medications used prophylactically for migraines are effective for cluster headaches. Drugs used for cluster headache prophylaxis include verapamil and certain anticonvulsants.

The approach to managing migraine headaches is both to try to prevent them (prophylactic therapy) and to treat the headache when it occurs. Treating the headache at the first sign of onset is usually more effective at getting rid of it than waiting to try to treat a full-blown migraine. Prophylactic medications include several classes of drugs originally intended for other problems (and covered in other chapters of this text). Beta-blockers (eg, metoprolol, propranolol) were originally used to treat high blood pressure. Antidepressants (amitriptyline and venlafaxine) and antiepileptic drugs (valproate and topiramate) can be used to prevent migraines. Usually, drugs used for prevention must be taken by the patient for several weeks to get the best effects. Patients need to be patient and keep a headache diary to monitor benefits. The reduction in headache frequency may take several weeks to occur.

Medications used to stop an attack that has already developed include drugs derived from ergot and the triptan (selective serotonin agonist) class. Both of these classes of drugs act by increasing serotonin activity to constrict blood vessels in the cranium and possibly reduce inflammation that is contributing to the headache.

Ergot-derived drugs include dihydroergotamine, which is available as an injection and as a nasal spray, and ergotamine tablets. Ergot is a fungus that grows on grain. In the Middle Ages, people who consumed this fungus experienced toxic symptoms, such as hallucinations, muscle spasms, and gangrene due to blood vessel constriction. In small doses, drugs derived from ergot cause constriction of blood vessels affected by the migraine reaction. These medications must not be used in women who are pregnant, because they can cause contractions of the uterus, resulting in miscarriage. In addition, they can cause nausea, vomiting, and numbness and tingling in the fingers, toes, and face. They should not be used at the same time or within a day of other ergots or triptans. Patients with heart and blood vessel disease should not use these medications. These medications are only used at the time of the attack and are limited in how often they may be repeated.

The triptan class (selective serotonin agonists) is the most popular drug class used to stop migraine attacks when ibuprofen or other OTC products are not sufficient. There are many drugs in this category: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. They all act in the same way but differ in how quickly they work, how long their effects last, dosage forms, and some drug interactions. Dosage forms in this class include tablets, orally dissolving tablets, and nasal sprays. Sumatriptan is the only drug in this class available for administration by subcutaneous (SUBQ) injection. These drugs are used at the first sign of migraine. Side effects can include dizziness, chest tightness, nausea, numbness, and sweating.1

Lasmiditan (Reyvow) is an oral serotonin receptor agonist that targets a different receptor than the triptans do.2 It is indicated for the treatment of acute migraine. Lasmiditan may cause intense drowsiness, and patients must not drive or operate machinery for several hours after taking this medication.

Because of the risk of serotonin syndrome, serotonin receptor agonists must be used with caution in patients who are taking other medications with activity affecting serotonin, such as selective serotonin reuptake inhibitors (SSRIs) and some antidepressants. Serotonin syndrome can cause abnormal muscle contractions, incoordination, and cardiovascular problems that can be life threatening.

A newer class of drugs specifically targets the activity of the trigeminal nerve, which has been implicated in migraine pain. Drugs in this class are called calcitonin gene-related peptide (CGRP) antagonists (“blockers”).2 Unlike ergot derivatives and triptans, drugs that target CGRP activity do not directly cause constriction of blood vessels. Some of these agents are monoclonal antibodies—proteins biologically engineered to bind CGRP or its receptors—and are used for migraine prevention. Most of the monoclonal antibody CGRP antagonists—erenumab, fremanezumab, and galcanezumab—are injected subcutaneously monthly. Fremanezumab may also be administered quarterly (every 3 months). Another CGRP blocking monoclonal antibody, eptinezumab, is administered by intravenous infusion every 3 months. Galcanezumab is also approved for the treatment of episodic cluster headaches. All may cause hypersensitivity reactions, usually mild, and injection site reactions. Erenumab may also cause constipation. Three other CGRP receptor antagonists are approved for use in the treatment of migraine. These agents—atogepant, ubrogepant and rimegepant (also called gepants)—differ from the monoclonal antibodies mentioned earlier, and are smaller molecules that block the ability of CGRP to bind to its receptors. The gepants are administered orally.2 Atogepant (Qulipta) is a once-daily oral dose for migraine prevention. Ubrogepant (Ubrelvy) is taken as a single oral dose when a migraine begins; the dose may be repeated two hours later if needed. Rimegepant (Nurtec) is an orally disintegrating tablet usually taken every other day to prevent migraine, but has been used to treat attacks in patients for whom triptans are ineffective or contraindicated.3 The gepants have a low incidence of side effects, but some patients experience nausea and fatigue or drowsiness.

STROKE

Stroke is a condition caused by either bleeding or a clot in the brain. A stroke due to bleeding in the brain is called a hemorrhagic stroke. A stroke due to a blood clot, which cuts off the blood supply to a section of the brain, is called a thrombotic stroke. In adults, thrombotic strokes are much more common than hemorrhagic strokes. Both kinds can cause severe debility or death. If a thrombotic stroke is detected early enough, medication may be able to dissolve the clot and resume the blood flow in the brain before permanent damage occurs. It is very important to recognize the symptoms of stroke and get help immediately. Symptoms of a stroke are a sudden severe headache, sudden weakness, or inability to talk or walk. Symptoms are usually on one side of the body. When a stroke is suspected, it is important to call for emergency help to get the patient to a hospital that is equipped to evaluate and treat stroke patients quickly. If the patient meets the qualifications for receiving medication (alteplase, described below) to break up the clot (for a thrombotic stroke that has occurred less than 3 hours ago, in a patient who has not had recent surgery or bleeding problems), the medication can often return the patient to his or her original level of functioning. Risks of stroke include uncontrolled high blood pressure, age, atrial fibrillation (a heart rhythm problem), and diabetes. In addition to treating the stroke, it is also important to treat blood pressure or heart rhythm problems. Patients are also routinely started on antiplatelet or anticoagulant therapy to reduce the risk of another clot forming. Antiplatelet agents used include aspirin, clopidogrel, and dipyridamole. (These agents are discussed in detail in Chapter 16.) The anticoagulant, apixaban, is another option. (See Chapter 26.) In addition, stroke patients are usually started on a statin drug (see Chapter 16), which has been shown to reduce the occurrence of future strokes.

Alteplase, also called tPA or tissue plasminogen activator, breaks up the clot (details in Chapter 16) that has caused a thrombotic stroke. Alteplase is administered by intravenous (IV) infusion as soon as the patient has been deemed to qualify for its use. Since alteplase can dissolve any clots in the body, a patient who has had recent surgery or bleeding problems usually cannot take this drug. Also, excessively high blood pressure must be brought to a safer level before alteplase is given.

PARKINSON’S DISEASE

Parkinson’s disease (PD) is a condition that affects about 1 million people in the United States. This disease is not common in younger patients, but the incidence increases with age. PD is named for an English physician, James Parkinson, who described people he met in the street who had similar characteristics. His description is still considered accurate today. The most common traits associated with PD are bradykinesia (general slowness of movement), muscular rigidity, balance problems, and tremor. The tremor is described as “pill rolling,” meaning the fingers (usually the forefinger and middle finger) rub against the thumb at a specific frequency. This tremor usually appears only on one side of the body in the early stages of the disease. Sometimes it is not present at all, but everyone with PD will have problems with slowness and rigidity.

Patients with PD are at a high risk for falls due to the rigidity and balance problems. Medications that can cause orthostatic hypotension (decreased blood pressure when getting out of bed or up from a chair), including some medications used to treat PD, can greatly increase this risk.

The movement problems due to PD are caused by the loss of dopamine activity in the area of the brain called the substantia nigra. By the time symptoms such as tremor and rigidity are detected, the brain has lost more than 80% of its dopamine activity. Some patients report earlier problems, such as loss of the sense of smell, depression, and rapid eye movement sleep behavior disorder in the years preceding the diagnosis of PD. Movement problems are not the only symptoms of PD. Most patients also have problems with oily skin, constipation, and drooling. Some will develop hallucinations (which can also be caused by PD medications), muscle spasms, and dementia.

In treating PD, the challenge is to give adequate amounts of medication so that the patient is able to move for as long as possible during the day without causing side effects due to those medications, such as hallucinations, dyskinesias (excessive abnormal movements), and dystonic reactions (muscle spasms). As the disease progresses, this balance becomes more difficult. In talking with a patient with PD, you may notice that the patient gives you very little nonverbal expressions of understanding. The face often appears mask-like, and the voice may be low in volume and range of expression. Answers may come slowly. These are also common PD traits and, unfortunately, they contribute to patient isolation. The patient’s handwriting often becomes very small (micrographia); the patient’s posture is usually stooped, and he or she often walks with a slow, shuffling gait. Because PD medications can also cause abnormal movements, the patient may appear to sway or writhe at certain times—usually when the drug is in its peak phase. As the disease progresses, the patient will usually need a cane, walker, or wheelchair.

Medications used to treat PD are aimed at increasing the dopamine activity in the brain. These medications fall into several categories. (See Medication Table 6-2.) Anticholinergic drugs are sometimes used. The neurotransmitter, acetylcholine, is in a balance with dopamine, as if they were on the opposing seats of a seesaw. When the level of dopamine is low, acetylcholine is overly active. Using an anticholinergic drug returns this balance closer to normal by reducing the activity of acetylcholine. Anticholinergic drugs are mostly used to reduce tremor activity. They can also be useful in reducing drooling. However, because most PD patients are elderly, anticholinergics must be used very cautiously because they can increase the risk of delirium and falls. Anticholinergic drugs used to treat PD include benztropine (Cogentin), biperiden (Akineton), and trihexyphenidyl (Artane).

Monoamine oxidase inhibitors are another class of medications that have the effect of increasing levels (and, thus, activity) of dopamine in the brain by inhibiting one of the enzymes, monoamine oxidase, that breaks down dopamine. They may be used alone in early stages of PD or in combination with other drugs as the disease progresses. These drugs are similar to amphetamines as they can interfere with sleep. For this reason, they must be dosed early in the day. Drugs in this category include selegiline (Eldepryl and Zelapar), rasagiline (Azilect), and safinamide (Xadago).

Amantadine, a drug that was originally used to prevent influenza A, was found to also have activity in PD patients. It has some anticholinergic activity, so it must be used with caution in elderly patients. In addition, since amantadine is partly removed from the body by the kidneys, patients with decreased kidney function will need lower daily doses. Amantadine is no longer marketed under the Symmetrel brand, but some doctors and patients may still use that name. There are two once-daily (extended-release) amantadine products, Gocovri and Osmolex ER, which are approved for use in Parkinson’s disease and also for drug-induced extrapyramidal reactions.

Levodopa is a drug that actually increases the amount of dopamine in the brain. Dopamine itself cannot be used for PD because it cannot enter the brain from the systemic circulation. Levodopa is an alteration of the dopamine molecule that can cross the blood–brain barrier into the brain, where it is converted to dopamine. Carbidopa, which accompanies levodopa in the brand-name products Sinemet, Parcopa, Rytary, and the enteric pump product, Duopa, prevents the conversion of levodopa to dopamine until the drug gets into the brain. Levodopa is one of the most important drugs used in managing PD, but it is not without its drawbacks. It has a fairly short duration of action, so it must be dosed several times daily. There are long-acting carbidopa/levodopa preparations, which can be taken twice a day, but the onset of action for long-acting carbidopa/levodopa is delayed, so the patient may need to take an immediate-release tablet early in the morning in order to be able to get moving sooner. In addition, as PD progresses many patients will take both the long-acting drug (two or three times a day) and also several doses of the immediate-release drug during the day.

Dopamine agonists are medications that mimic the effects of dopamine on the dopamine receptors in the brain. Since they act in a similar manner to dopamine, they can postpone the need for carbidopa/levodopa. They are often an early choice for younger patients with PD. Dopamine agonists include bromocriptine (Parlodel), pramipexole (Mirapex), ropinirole, and the transdermal patch, rotigotine (Neupro). In addition, the injectable dopamine agonist apomorphine (Apokyn) is used to provide relief from “off episodes,” in which patients become frozen and unable to move. All drugs that increase dopamine activity, including both dopamine agonists and levodopa, have the potential to cause hallucinations, dyskinesias (abnormal movements), and unusual obsessive behavior. Some patients taking these medicines have developed a new compulsion to gamble or obsession with sex. These effects do not happen in most patients with PD using these medicines, but patients should be counseled to report any unusual thoughts or behavior to the doctor. In addition, these medicines have a side effect known as “sleep attacks.” There are reports of patients suddenly, without preliminary drowsiness, falling asleep. Patients should be warned of this possibility, especially if they are still operating automobiles or machinery.

COMT inhibitors (catechol-O-methyl transferase) are also used to extend the activity of dopamine by reducing another enzyme responsible for its break down. Available COMT inhibitors include entacapone, opicapone, and tolcapone. Because tolcapone has been reported to cause liver damage and must be monitored with regular liver enzyme tests, and opicapone has no generic equivalent, entacapone is much more commonly used. These drugs have no direct activity on PD and must always be given along with carbidopa/levodopa. There is a combination product, Stalevo, that combines carbidopa, levodopa, and entacapone into one product for ease of use. COMT inhibitors have the potential to cause diarrhea.

As PD progresses, patients may develop “off spells,” when they become unable to move. Off spells may occur at random or predictable times during the day. Some PD medications are used only for patients who experience off spells. Daily oral istradefylline (Nourianz), an adenosine receptor antagonist, may be added to a patient’s carbidopa/levodopa regimen when off spells become a regular problem. It is not known specifically how this product helps to prevent off spells. Tobacco use may reduce this drug’s effectiveness, so a higher dose may be needed if a patient smokes a pack or more of cigarettes daily. For acute treatment, apomorphine (Apokyn) is an injectable product used for off spells. Because of several problematic side effects, it is not often used. Apomorphine causes severe nausea, and the patient needs to take trimethobenzamide (Tigan) for 3 days before beginning apomorphine therapy to prevent nausea. Most drugs used to treat nausea, such as promethazine and metoclopramide, act against dopamine and make PD symptoms worse, so they should not be used in patients with PD. In addition, the type 3 serotonin (5-HT₃) receptor antagonists, such as ondansetron (Zofran), are contraindicated with apomorphine. (These agents are addressed specifically in Chapter 21.) Levodopa inhalation powder (Inbrija) is another product for off spells that is effective within about 10 minutes of use and lasts up to one hour. Patients should inhale the powder slowly through their mouths to avoid gagging and coughing. Istradefylline (Nourianz) is also used for off spells.

Patients with PD will often need other medications to help manage constipation, skin problems, depression, sleep disturbances, and pain. Sometimes an antipsychotic medication is needed to help manage hallucinations or delusions that may occur in PD or with PD medications. Most antipsychotics are not good choices due to their activity against dopamine. Most practitioners prefer to use low doses of quetiapine or sometimes clozapine in patients with PD. Pimavanserin (Nuplazid) is an atypical antipsychotic that is approved only for treatment of hallucinations and delusions associated with PD.

DEMENTIA

Dementia is a condition in which a person declines in cognitive, or mental, level of functioning. Some of the characteristics of dementia are impairment of memory, especially of recent events; loss of the ability to do everyday cognitive tasks, such as following a grocery list, paying bills, or managing a checkbook; loss of the ability to follow directions; and decline in the ability to name common objects, such as books, paper clips, and shoelaces. The patient with dementia may become confused or lost in a formerly familiar setting. There are several types of dementia, the most common one being Alzheimer’s disease, which is a progressive dementia that ends with the patient being bedfast and unable to walk, talk, or recognize family. Death follows when the patient loses the will to eat or develops an infection such as pneumonia or a urinary tract infection. The duration of the disease varies but averages about 10 years from onset to death. Other types of dementia include vascular dementia, in which the mental decline is due to strokes or other blood vessel disease in the brain; Lewy body dementia, which may exist alone or as part of PD and often includes visual hallucinations (animals, strange people in the house, children playing) and may lead to the patient becoming suspicious of caregivers; and frontotemporal dementia, which involves dramatic changes in personality and the ability to make judgments.

Dementia is assessed by tests such as the Mini Mental Status Exam, in which the examiner asks the patient to repeat phrases, name objects, follow commands, and do simple tasks. The score given is an assessment of the severity of the disease. Because of the expected decline, it is better for a patient to be assessed early in the disease so the patient can make decisions about supportive care, living situation, driving, and other important issues.

Dementia cannot be cured. Medication may help to slow the decline and treat behavioral issues. Currently, nearly one-half of elderly people over the age of 85 years have symptoms of cognitive impairment. Studies are ongoing to see if the incidence of dementia can be lowered with interventions made earlier in life. There are suggestions that good nutrition, regular exercise, lifelong learning, and avoiding or managing diabetes, hypertension, and depression may reduce the likelihood of dementia if these changes are made by middle age.

Medications specifically indicated to treat dementia include cholinesterase inhibitors and memantine. (See Medication Table 6-3.) Most of these agents have a formal Food and Drug Administration (FDA) approval only for Alzheimer’s disease, but are usually also useful for Lewy body and vascular dementias. Frontotemporal dementia usually does not respond to medications used for Alzheimer’s disease. In addition, other medications, such as antidepressants, mood stabilizers, sedative-hypnotics, and antipsychotics are used for depression, sleep, and behavioral problems. Usually initial doses used are lower than would be used in a younger person. In addition, the use of antipsychotics is controversial—they help with behavioral problems, such as aggression and hallucinations, but they have been shown to increase the risk of stroke and other events in patients with dementia. In addition, most antipsychotics should be avoided in patients with Lewy body dementia, since they can exacerbate PD symptoms that often accompany that condition.

The effects of plaques and nerve tangles in the brain that are characteristic of Alzheimer’s disease reduce the activity of acetylcholine, causing many symptoms. The cholinesterase inhibitors work by reducing the metabolism of acetylcholine in the brain, thus increasing its activity. Cholinesterase inhibitors have been shown to slow the decline in mental function by at least several months. The drugs, which include donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), should be started at a lower dose and titrated up to the desired dose in order to improve patient tolerance. Common side effects are stomach upset, decreased appetite, and weight loss. These drugs may increase the risk of gastrointestinal (GI) bleeding in patients with ulcers and must be used with care in patients with heart rhythm problems.

Memantine (Namenda) is another drug that may be helpful in patients with dementia. Memantine works by decreasing the activity of N-methyl-D-aspartate (NMDA) receptors in the brain. These receptors are acted on by glutamate, and the result is believed to worsen some of the symptoms of Alzheimer’s disease. Since memantine is mostly eliminated by the kidneys, the dose should be reduced in patients with renal impairment. Memantine has a titration schedule for achieving the desired dosage and is usually well tolerated, but dizziness, headache, constipation, and confusion have been reported in a small percentage of patients.

EPILEPSY

Epilepsy is a condition that is really a collection of disorders. Due to excessive electrical activity in the brain, a person will partially or completely lose consciousness. The person will have either localized movements, such as an arm shaking, or generalized movements, such as arms and legs jerking wildly. Seizures usually last only a few minutes, and the patient regains consciousness but often feels tired or confused for several hours. If a seizure lasts more than a few (eg, 5) minutes, it can become life threatening and needs to be treated as an emergency.

Epilepsy is diagnosed by taking a history from the patient, doing a neurologic examination, and checking an MRI scan and an EEG. The EEG is the most beneficial tool for detecting abnormal brain waves. Often, a neurologist can detect abnormal brain waves when a patient is not having a seizure, but sometimes the brain looks normal at that time.

There are many medications available to reduce the number of seizures a patient has. The goal is to have no seizures and no side effects. Many patients can be treated successfully with the first drug that is tried. Unfortunately, some patients have epilepsy that is more difficult to treat and will have to try several different medications or use two or three medications together. Many epilepsy medications, especially the older ones, are prone to causing drug interactions with other medications. The physician and pharmacist must always check for these interactions. Some medications will decrease the blood levels of the antiepileptic drug, and that could cause the patient to have a seizure.

Some situations that can increase the possibility of having a seizure are missing doses of medicine, not getting enough sleep, stress or infections, and, for women, different phases of the menstrual cycle. Patients with epilepsy, especially when seizures are not well controlled, often have problems with their memory. It is helpful to use a seizure calendar and medication compliance aids, such as pill boxes, to monitor the effectiveness of the medication and improve adherence to therapy. In addition, patients may contact the Epilepsy Foundation for assistance in meeting the challenges of this condition.

Treatment of epilepsy relies on medication. (See Medication Table 6-4.) There has been a dramatic increase in the number of drugs available to treat epilepsy in the past 20 years, but the older drugs are also commonly used. Certain drugs are more effective for particular types of epilepsy. For example, ethosuximide, valproate, and a few others are effective in treating absence seizures, but some other medications, such as carbamazepine and phenytoin, are not—indeed, these drugs can increase the frequency of seizures in these patients.

For about half of patients with epilepsy, the first drug their doctor tries will be effective in controlling their seizures. If the patient tolerates the drug well, treatment can continue with that medication. For many other patients, their epilepsy is more difficult to control and will require trials of different medications and sometimes combinations of medications. Patients with difficult to control seizures often benefit from a referral to a neurologist who specializes in epilepsy.

Many antiepileptic drugs have the potential for drug interactions. These drugs can interact with other antiepileptics and also other medications the patient may take, such as antidepressants and warfarin. The effects of these interactions must be recognized, especially when adding or withdrawing a drug from the patient’s therapy. In addition, some antiepileptics have a narrow range of blood levels between which they are effective but not toxic. Some doctors test the blood of their patients to follow the levels, and others just rely on the patient’s response and monitor for side effects. Patients with particular needs in epilepsy management are women who may become pregnant. Some antiepileptic drugs may reduce the effectiveness of hormone contraceptives or have the potential to cause birth defects. The choice of drugs used to treat epilepsy will depend on issues such as these in addition to patient tolerance and effectiveness of a drug in treating the patient’s seizures.

The following sections discuss medications used to treat epilepsy, some particular features of the medicine, and possible side effects. Some important drug interactions are listed, but a more complete reference should be consulted for a thorough discussion of possible interactions. In general, antiepileptic drugs should be started at low doses and gradually increased to the desired dose to reduce the chance of undesirable effects. Likewise, when taking a patient off an antiepileptic drug, the dose should be lowered gradually—usually over several weeks—to reduce the risk of seizures. In addition, when drugs that have interactions are used together, attention must be paid to the effect that removal of one drug may have on the levels of the continued drug. In addition to all benzodiazepines and barbiturates, some other antiepileptic drugs (eg, pregabalin, lacosamide) are controlled substances.

MULTIPLE SCLEROSIS

MS is a disease that affects nerves, causing a dramatic slowing in the conduction of electrical impulses. It is caused by an inflammatory process that attacks myelin, a protective insulator of the axon of nerve cells. When the myelin is damaged or destroyed, the areas innervated by those nerves lose their function (Figure 6-1). The symptoms of MS vary, depending on which area of the brain is having its myelin attacked. These attacks come and go, with disability followed by recovery, or they continue to progress. Eventually many patients become unable to walk without assistance. Muscle weakness, muscle spasms, problems with constipation, bladder incontinence, and vision problems are common developments.

The treatment of MS includes treatment of acute exacerbations, the use of disease-modifying therapy to reduce exacerbations, and the use of other medications for symptomatic problems such as pain, spasticity, fatigue, constipation, and urinary problems.

The medications used to treat MS are meant to reduce the number of relapses the patient experiences. These medications are known as immunomodulators. Other medications are used for treatment of the symptoms associated with MS, such as fatigue, depression, constipation, or muscle spasms. None of these medications will cure the disease. (See Medication Table 6-5.)

For acute exacerbations, high doses of corticosteroids are used, usually intravenously. Methylprednisolone is given IV for 3 to 10 days, and symptoms usually improve after 5 days or so. The main key to management of MS is disease-modifying therapy. Several medications are used for this purpose. The specific mechanisms of action are not known for all of these products but, as a group, they interfere, in different ways, with the immune system’s attack on myelin. The choice of therapy depends on the characteristics of the patient’s disease, such as relapsing or progressive, and how the patient responds and tolerates a medication. A challenge to compliance is that these medications often cause considerable side effects and are inconvenient and expensive. They are intended to reduce the rate of relapses, but the patient may not realize that benefit for a year or more. Interferons (beta_1b and beta_1a) are one class in this category. Their exact mechanism of action is not known, but they are believed to reduce the immune response that attacks myelin. Interferons are administered either intramuscularly (IM) or subcutaneously. When administered according to direction, which varies by product, they can reduce the rate of MS relapses. However, these medications often cause side effects that discourage compliance, including flu-like symptoms, injection site irritation, and depression. Brand names of interferon drugs include Rebif, Plegridy, Extavia, and Betaseron.

Glatiramer acetate (Copaxone, Glatopa) is an alternative to interferons in many patients and may be better tolerated. Its mechanism is not fully understood, but it may act as a substitute for receptors that are attacked by the immune response in MS. Glatiramer is administered as a daily or three times weekly SUBQ injection, and it must be stored in the refrigerator. Glatiramer is very expensive but is gaining more attention as a useful agent for many MS patients. Some patients (about 10%) may develop flushing and tightness in the chest and difficulty breathing the first time they use this medication, but this reaction usually goes away in about 20 minutes.

Natalizumab (Tysabri), ocrelizumab (Ocrevus), and alemtuzumab (Lemtrada) are monoclonal antibodies that work by preventing white blood cells from attacking myelin in the brain. They are alternatives for patients who continue to have relapses while on other medications. All three are administered as IV infusions, but they have different schedules. These products are usually well tolerated, but patients must be monitored during and after infusions for reactions. Common side effects include headache, fatigue, and nausea. These products, because of their action in reducing the immune response, may increase the patient’s susceptibility to certain infections.

Mitoxantrone (Novantrone) is a chemotherapy drug that is also used for progressing forms of MS and for difficult cases of MS that have not responded well to other medications. It inhibits white blood cell activity in attacking nerve cells. Because of the possible reduced heart function that can be caused by this medication, there is a maximum total lifetime dosage that should not be exceeded. Other side effects include nausea, vomiting, hair loss, and menstrual problems.3 Cladribine (Mavenclad) is another drug that resembles a chemotherapy medication. It has approval for certain MS patients who meet its criteria. This medication is taken orally, and only a few days over the course of two years, but has limitations due to several precautions, including the possibility of causing malignancies.

Medications used to manage fatigue, urinary problems, constipation, muscle spasms, depression, and other symptoms of MS are also used to manage these symptoms due to other causes, which are discussed in the appropriate chapters of this text. Dalfampridine (Ampyra) is a medication approved specifically to improve the walking ability of people with MS. It works by blocking potassium channels, which increase nerve signal conduction through axons. Dalfampridine is an oral medication. It is contraindicated in patients who have had seizures and in those who have decreased kidney function.

In addition to medications, patients with MS need to avoid becoming excessively fatigued or overheated. In spite of the difficulties associated with the disease, patients will usually have a normal life expectancy. The degree of disability varies dramatically from one patient to another.

NEUROPATHIC PAIN

Neuropathic pain is a particular pain condition caused by sensitivity, excessive activity, or damage in nerves. Characteristics of neuropathic pain are numbness, burning, tingling, shooting, and electric shock-like pain. Neuropathic pain can occur due to neuropathies caused by diabetes, nerve pain due to MS, pain in a nerve root due to shingles, and pressure on the spinal cord, such as spinal stenosis. Neuropathic pain can be treated with medications that work on the neurotransmitters that transmit pain signals. Medications that we have already discussed include tricyclic antidepressants (used at low doses); many of the anticonvulsants, such as gabapentin, pregabalin, and carbamazepine; and specific analgesics, such as tramadol and methadone.

SLEEP DISORDERS

When we think of sleep disorders, we usually think of problems falling asleep. That is the most common problem for Americans, but there are many other conditions that cause problems with the sleep cycle. To begin we should discuss normal sleep. Our bodies react to decreasing amounts of light to increase the production of melatonin in the brain. Melatonin causes us to feel drowsy and fall asleep. In addition there is a circadian rhythm that determines periods of time during the day that we sleep or are alert. When we fall asleep, we initially enter a light sleep, then proceed through deeper phases to deep sleep (phases 3 and 4). Then we enter a lighter sleep in which we do most of our dreaming, the rapid eye movement phase (REM sleep), and then the cycle begins again. We go through this cycle several times every night, with the amount of time in the deep and REM phases changing as the night progresses.

People with sleep disorders may have problems falling asleep, problems staying asleep, and problems waking up too early and being unable to go back to sleep. Sleep problems may be transient or temporary—resulting from some change or stress in the patient’s life—or chronic and continuing for a long period of time. Some patients also have unusual behaviors during sleep in which they may walk, cook, eat, or do other activities that are better left to the waking hours. During REM sleep behavior disorder, a patient will thrash around as he acts out his dreams (normally we do not move during dreaming.)

SUMMARY

The central nervous system is complex and is connected to every part of the body in some way. This means there are many different kinds of malfunctions that can occur and many different conditions that can result. Some of these can be completely relieved, while others can be treated to lessen their impact on the patient’s daily life. Often, multiple therapies, including medications and other treatments, must be tried and/or continued before the patient’s condition improves.

CHAPTER RESOURCES

AHFS Drug Information. AHFS Clinical Drug Information. Bethesda, MD: American Society of Health-System Pharmacists.

Bainbridge JL, Miravalle A, Wong P, Makelky MJ. Multiple sclerosis. In: DiPiro JT, Yee GC, Posey L, et al. eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. New York, NY: McGraw-Hill; 2020.

Nguyen VV, Dergalust S, Chang E. Epilepsy. In: DiPiro JT, Yee GC, Posey L, et al. eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. New York, NY: McGraw-Hill, 2020.

REVIEW QUESTIONS

1. Describe some differences between disorders described as neurologic and those considered psychiatric.

2. What are some of the distinguishing characteristics of migraine headaches?

3. List some of the signs of stroke and describe what measures should be taken if stroke is suspected.

4. What causes the symptoms of Parkinson’s disease, and what is the common goal of most of the medications used to treat it, regardless of their mechanism of action?

5. What types of medication therapy are used in the treatment of multiple sclerosis?

MEDICATION TABLES WITH REPRESENTATIVE AGENTS FOR EACH DISORDER