Etiology

Epileptic seizures are idiopathic in more than half of all affected patients.^2,3 Vascular (cerebrovascular disease) and developmental abnormalities (cavernous malformation), intracranial neoplasms (gliomas), and head trauma are causative in about 35% of adult cases. Other common causes include hypoglycemia, drug withdrawal, infection, and febrile illness (e.g., meningitis, encephalitis). Seizures occur with genetic conditions such as Down syndrome, tuberous sclerosis, and neurofibromatosis and are associated with several genetic abnormalities that result in neuronal channel dysfunction.^2,3

Seizures sometimes can be evoked by specific stimuli. Approximately 1 of 15 patients reports that seizures occurred after exposure to flickering lights, monotonous sounds, music, or a loud noise.^2,4 Syncope and diminished oxygen supply to the brain also are known to trigger seizures. It is valuable for the dentist to know what factors have the potential to exacerbate a seizure in a particular patient, so that certain stimuli can be avoided.²

Pathophysiology and Complications

The basic event underlying an epileptic seizure is an excessive focal neuronal discharge that spreads to thalamic and brain stem nuclei. The cause of this abnormal electrical activity is not precisely known, although a number of theories have been put forth.^2,3 These include altered sodium channel function, altered neuronal membrane potentials, altered synaptic transmission, diminution of inhibitory neurons, increased neuronal excitability, and decreased electrical threshold for epileptic activity. During the seizure, blood becomes hypoxic, with consequent development of lactic acidosis.^2,3

Approximately 60% to 80% of patients with epilepsy achieve complete control over their seizures within 5 years; the remainder achieve only partial or poor control.^2,3,5 A significant problem in the medical management of epileptic patients is one of compliance (i.e., adherence to prescribed treatment regimens including medication). This problem is common to many chronic disorders, such as hypertension, because patients may have to take medication for the rest of their lives, even though they remain asymptomatic. Evidence suggests that patients who have epilepsy from an early age have a higher incidence of future complications and die at an earlier age. Noncompliance may be a clinically important consideration in dental patients because it is associated with a higher risk of later complications that may lead to death.⁴ Complications of seizures include trauma (as a result of falls) to the head, neck, and mouth and aspiration pneumonia. Also, frequent and severe seizures are associated with altered mental function, dullness, confusion, argumentativeness, and increased risk of sudden death (about 1 in 75 persons in this group die annually).^2,3

Signs and Symptoms

The clinical manifestations of generalized tonic-clonic convulsions (grand mal seizures) are classic. An aura (a momentary sensory alteration that produces an unusual smell or visual disturbance) precedes the convulsion in one third of patients. Irritability is another premonitory signal. After the aura warning, the patient emits a sudden “epileptic cry” (caused by spasm of the diaphragmatic muscles) and immediately loses consciousness. The tonic phase consists of generalized muscle rigidity, pupil dilation, rolling of the eyes upward or to the side, and loss of consciousness. Breathing may stop because of spasm of respiratory muscles.^2,3 This phase is followed by clonic activity consisting of uncoordinated beating movements of the limbs and head, forcible jaw closing, and up and down head rocking.^2,3 Urinary incontinence is common, but fecal incontinence is rare. The seizure (ictus) usually does not last longer than 90 seconds; thereafter, movement ceases and muscles relax, with a gradual return to consciousness, accompanied by stupor, headache, confusion, and mental dulling. Several hours of rest or sleep may be needed for the patient to regain full cognitive and physical abilities.^2,3

Laboratory Findings

The diagnosis of epilepsy generally is based on the history of seizures and presence of abnormalities on the electroencephalogram (EEG).^2,3 Seizures produce characteristic spike and sharp wave patterns on the EEG tracing. Serial recordings during sleep deprivation, which can induce seizures, may help to establish the diagnosis. Other diagnostic procedures that are useful for ruling out other causes of seizures include computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), lumbar puncture, serum chemistry profiles, and toxicology screening.^2,3

Medical Management

The medical management of epilepsy usually is based on long-term drug therapy. Phenytoin (Dilantin), carbamazepine (Tegretol), and valproic acid are considered first-line agents for treatment of this disease. Several other drugs are available for control of generalized tonic-clonic seizures^5,6 (Table 27-1). These drugs reduce the frequency of seizures by elevating the seizure threshold of motor cortex neurons, depressing abnormal cerebral electrical discharge, and limiting the spread of excitation from abnormal foci. Phenytoin and carbamazepine are efficient at blocking sodium or calcium channels of motor neurons.^5–7 Many of the other antiepileptic drugs augment γ-aminobutyric acid (GABA), which inhibits glutamate activity—the major determinant of brain excitability. Adverse effects of phenytoin include anemia, ataxia, gingival overgrowth, cosmetic changes (coarsening of facial features, hirsutism, facial acne), lethargy, skin rash, and gastrointestinal disturbances. Phenobarbital, which is considered a second-line drug, can induce hepatic microsomal enzymes that promote the metabolism of concurrently used drugs.⁸ Several antiseizure medications (see Table 27-1) may cause drowsiness, sedation, ataxia, weight gain, cognitive impairment, and hypersensitivity reactions.^5–7 Adverse effects are more common at the start of therapy, when drugs are administered rapidly or at high dose. For these reasons, and to facilitate compliance, single-drug therapy and a slow increase in dose are recommended. Unfortunately, the use of combination therapy frequently is necessary for seizure control.^5–7 Drug therapy usually is continued in children until a 1- to 2-year seizure-free period is attained, or until around age 16 years. Attempts to taper the antiepileptic drug regimen are made thereafter.

Vagus nerve stimulation (VNS) is reserved for patients who have been unable to achieve satisfactory seizure control with several medications, and it is an option for some before brain surgery. The mechanism of VNS is similar to that of an implantable cardiac pacemaker, in which a subcutaneous pulse generator is implanted in the left chest wall and delivers electrical signals to the left vagus nerve through a bipolar lead. The stimulated vagus nerve provides direct projection to regions in the brain potentially responsible for the seizure. The VNS device generally is used in combination with antiepileptic medications.^5–7

Medical Considerations

The first step in the management of an epileptic dental patient is identification of the patient as having the disorder (Box 27-2). This is best accomplished by the medical history and by discussion with the patient or family members. Once a patient with epilepsy has been identified, the dental practitioner must learn as much as possible about the seizure history, including the type of seizures, age at onset, cause (if known), current and regular use of medications, frequency of physician visits, quality of seizure control, frequency of seizures, date of last seizure, and any known precipitating factors. In addition, a history of previous injuries associated with seizures and their treatment may be helpful.

Fortunately, most epileptic patients are able to attain good control of their seizures with anticonvulsant drugs and are therefore able to receive normal routine dental care. In some instances, however, the history may reveal a degree of seizure activity that suggests noncompliance or a severe seizure disorder that does not respond to anticonvulsants. For these patients, a consultation with the physician is advised before dental treatment is rendered. A patient with poorly controlled disease may require additional anticonvulsant or sedative medication, as directed by the physician.

Patients who take anticonvulsants may suffer from the toxic effects of these drugs, and the dentist should be aware of these manifestations. In addition to the more common adverse effects (see Table 27-1), allergy may be seen occasionally as a rash, erythema multiforme, or worse (e.g., Stevens-Johnson syndrome). Phenytoin, carbamazepine, and valproic acid can cause bone marrow suppression, leukopenia, and thrombocytopenia, resulting in an increased incidence of microbial infection, delayed healing, and gingival and postoperative bleeding. Valproic acid can decrease platelet aggregation, leading to spontaneous hemorrhage and petechiae.⁸

Propoxyphene and erythromycin should not be administered to patients who are taking carbamazepine because of interference with metabolism of carbamazepine, which could lead to toxic levels of the anticonvulsant drug.^5–7 Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) (see Table 27-1) should not be administered to patients who are taking valproic acid, because these agents can further decrease platelet aggregation, leading to hemorrhagic episodes. No contraindication has been identified to the use of local anesthetics in proper amounts in these patients. Patients who have a VNS device implanted in the chest do not need antibiotic prophylaxis before undergoing invasive dental procedures.^5–7

Seizure Management

Despite consistent use of appropriate preventive measures by both dentist and patient, the possibility always exists that an epileptic patient may experience a generalized tonic-clonic convulsion in the dental office. The dentist and office staff members should anticipate and be prepared for such events. Preventive measures include knowing the patient’s history, scheduling the patient at a time within a few hours of taking the anticonvulsant medication, using a mouth prop, removing dentures, and discussing with the patient the urgency of mentioning an aura as soon as it is sensed. The clinician also should be aware that irritability often is a symptom of impending seizure. With a premonitory stage of sufficient duration, 0.5 to 2 mg of lorazepam can be given sublingually, or diazepam 2 to 10 mg can be given intravenously.⁹

If the patient has a seizure while in the dental chair, the primary task of management is to protect the patient and try to prevent injury. No attempt should be made to move the patient to the floor. Instead, the instruments and instrument tray should be cleared from the area, and the chair should be placed in a supported supine position (Figure 27-1). The patient’s airway should be maintained patent. No attempt should be made to restrain or hold the patient down. Passive restraint should be used only to prevent injury that may result when the patient hits nearby objects or falls out of the chair.^10,11

FIGURE 27-1 Dental chair in the supine position with the back supported by the operator’s or assistant’s stool.

If a mouth prop (e.g., a padded tongue blade between the teeth to prevent tongue biting) is used, it should be inserted at the beginning of the dental procedure (see Box 27-2). Trying to insert a mouth prop is not advised during the seizure, because doing so may damage the patient’s teeth or oral soft tissue and may be nearly impossible. An exception is the case in which the patient senses an impending seizure and can cooperate.^10,11

A grand mal seizure generally does not last longer than a few minutes. Afterward, the patient may fall into a deep sleep from which he or she cannot be aroused. Oxygen (100%), maintenance of a patent airway, and mouth suction should be provided during this phase. Alternatively, the patient can be turned to the side to control the airway and to minimize aspiration of secretions. Within a few minutes, the patient gradually regains consciousness but may be confused, disoriented, and embarrassed. Headache is a prominent feature during this period. If the patient does not respond within a few minutes, the seizure may be associated with low serum glucose, and delivery of glucose may be needed.^10,11

No further dental treatment should be attempted after a generalized tonic-clonic seizure, although examination for sustained injuries (e.g., lacerations, fractures) should be performed. In the event of avulsed or fractured teeth (Figure 27-2) or a fractured appliance, an attempt should be made to locate the tooth or fragments to rule out aspiration. A chest radiograph may be required to locate a missing fragment or tooth.^10,11

FIGURE 27-2 Fracture of teeth and laceration of lower lip sustained during a grand mal seizure.

(Courtesy Gerald A. Ferretti, DDS, Lexington, Kentucky.)

In the event that a seizure becomes prolonged (status epilepticus) or is repeated, intravenous lorazepam (0.05 to 0.1 mg/kg) 4 to 8 mg, or 10 mg diazepam, generally is effective in controlling it. Lorazepam is preferred by many experts because it is more efficacious and lasts longer than diazepam.^2,3 Oxygen and respiratory support should be provided, because respiratory function may become depressed. If the seizure lasts longer than 15 minutes, the following protocol should be implemented: secure intravenous access, repeat lorazepam dosing, administer fosphenytoin, and activate the emergency medical services (EMS) system.^10,11

Treatment Planning Considerations

Because gingival overgrowth is associated with phenytoin administration, every effort should be made to maintain a patient at an optimal level of oral hygiene. This may require frequent visits for monitoring of progress. If gingival overgrowth is significant, surgical reduction will be necessary. This correction must be accompanied by an increased awareness of oral hygiene needs and a positive commitment by the patient to maintain oral cleanliness.

A missing tooth or teeth should be replaced if possible to prevent the tongue from being caught in the edentulous space during a seizure (as commonly happens). Generally, a fixed prosthesis or implant is preferable to a removable one. (The removable prosthesis becomes dislodged more easily.) For fixed prostheses, all-metal units should be considered when possible, to minimize the chance of fracture. When placing anterior castings, the dentist may wish to consider using three-quarter crowns or retentive nonporcelain facings.

Removable prostheses are, nevertheless sometimes constructed for epileptic patients. Metallic palates and bases are preferable to all-acrylic ones. If acrylic is used, it should be reinforced with wire mesh.

Oral Complications and Manifestations

The most significant oral complication seen in epileptic patients is gingival overgrowth, which is associated with phenytoin (Figure 27-3) and rarely with valproic acid and vigabatrin.^7,10 The incidence of phenytoin-induced gingival overgrowth in epileptic patients ranges from 0% to 100%, with an average rate of approximately 42%. A greater tendency to develop gingival overgrowth occurs in youngsters than in adults. The anterior labial surfaces of the maxillary and mandibular gingivae are most commonly and severely affected.^7,10

FIGURE 27-3 Phenytoin-induced gingival overgrowth.

(Courtesy H. Abrams, Lexington, Kentucky.)

Meticulous oral hygiene is important for preventing overgrowth and significantly decreasing its severity. Good home care must always be combined with the removal of irritants, such as overhanging restorations and calculus. Frequently, enlarged tissues interfere with function or appearance, and surgical reduction may become necessary.

Traumatic injuries such as broken teeth, tongue lacerations, and lip scars also are common in patients who experience generalized tonic-clonic seizures. Stomatitis, erythema multiforme, and Stevens-Johnson syndrome are rare adverse effects associated with the use of phenytoin, valproic acid, lamotrigine, phenobarbital, and carbamazepine. These complications are more common during the first 8 weeks of treatment.^7,10

Incidence and Prevalence

Stroke is one of the most significant health problems in the United States. Stroke is the third leading cause of death (behind heart disease and cancer) in the United States, with 275,000 Americans dying of stroke annually.¹² Each year in the United States, about 700,000 people experience new or recurrent stroke. This figure translates to the occurrence of one stroke about every minute, and 75% of persons survive their stroke.^12,13

Hypertension is the most important risk factor for ischemic and hemorrhagic stroke.^12,13 The incidence of stroke increases directly in relation to the degree of elevation of systolic and diastolic arterial blood pressure above threshold values. More important, conclusive evidence accrued since 1980 indicates that control of hypertension prevents strokes. Metaanalyses of randomized controlled trials confirm an approximate 30% to 40% reduction in stroke risk with lowering of blood pressure.^12,13

Approximately 7% to 10% of men and 5% to 7% of women older than 65 years have asymptomatic carotid stenosis of greater than 50%. Epidemiologic studies suggest that the rate of unheralded stroke evolving ipsilateral to a stenosis is about 1% to 2% annually.^12,13

Nonvalvar atrial fibrillation carries a 3% to 5% annual risk for stroke, with the risk becoming even higher in the presence of advanced age, previous transient ischemic attack (TIA) or stroke, hypertension, impaired left ventricular function, and diabetes mellitus.^12,13

In epidemiologic studies, the risk for stroke in smokers is almost double that in nonsmokers, but the risk becomes essentially identical to that in nonsmokers by 2 to 5 years after quitting. The relative risk for stroke is two to six times greater for patients with insulin-dependent (type 1) diabetes.^12,13 An association with race has been recognized: Compared with whites, African Americans are at 38% greater risk for a first stroke. Also, 40,000 more women than men have a stroke each year. Risk of stroke increases with age; however, on average, 28% of people who have a stroke are younger than 65 years.^12–14 A total of 4.7 million stroke survivors live in the United States, and an average dental practice of 2000 adult patients will include about 31 patients who have had or will experience a stroke.

Etiology

Stroke is caused by the interruption of blood supply and oxygen to the brain as a result of ischemia or hemorrhage. The most common type is ischemic stroke induced by thrombosis (in 60% to 80% of cases) of a cerebral vessel. Ischemic stroke also can result from occlusion of a cerebral blood vessel by distant emboli. Hemorrhage causes about 15% of all strokes and carries a 1-year mortality rate greater than 60%.^12,13

Cerebrovascular disease is the primary factor associated with stroke. Atherosclerosis and cardiac pathosis (myocardial infarction, atrial fibrillation) increase the risk of thrombolic and embolic strokes, whereas hypertension is the most important risk factor for intracerebral hemorrhagic stroke.^12,13 Approximately 10% of persons who have had a myocardial infarction will have a stroke within 6 years.^12,13 Additional factors that increase the risk for stroke include the occurrence of transient ischemic attacks, a previous stroke, high dietary fat, obesity and elevated blood lipid levels, physical inactivity, uncontrolled hypertension, cardiac abnormalities, diabetes mellitus, elevated homocysteine levels, elevated hematocrit, elevated antiphospholipid antibodies, heavy tobacco smoking, increasing age (risk doubles each decade after the age of 65 years), and periodontal disease.^12,13 Increased risk for hemorrhagic stroke also occurs with use of phenylpropanolamine, an α-adrenergic agonist.^12,13

Pathophysiology and Complications

Pathologic changes associated with stroke result from infarction, intracerebral hemorrhage, or subarachnoid hemorrhage. Cerebral infarctions most commonly are caused by atherosclerotic thrombi or emboli of cardiac origin. The extent of an infarction is determined by a number of factors, including site of the occlusion, size of the occluded vessel, duration of the occlusion, and collateral circulation. The production and circulation of proinflammatory cytokines, the occurrence of clotting factors, and arterial inflammation contribute to platelet aggregation. Neurologic abnormalities result from excitotoxicity, free radical accumulation, inflammation, mitochondrial and DNA damage, and apoptosis of the region supplied by the damaged artery.^12,13

The most common cause of intracerebral hemorrhage is hypertensive atherosclerosis, which results in microaneurysms of the arterioles (Figure 27-4). Vessels within the circle of Willis often are affected (Figure 27-5). Rupture of these microaneurysms within brain tissue leads to extravasation of blood, which displaces brain tissue, causing increase in intracranial volume until resultant tissue compression halts bleeding. Hemorrhagic strokes also may be caused by subarachnoid hemorrhage. The most common cause of subarachnoid hemorrhage is rupture of a saccular aneurysm at the bifurcation of a major cerebral artery.^15,16

FIGURE 27-4 Cerebral infarction in a patient who had chronic hypertension.

FIGURE 27-5 Aneurysm of the middle cerebral artery.

The most serious outcome of stroke is death, which occurs in 8% of those who experience ischemic strokes and 38% to 47% of those with hemorrhagic strokes within a month of the event. Overall, about 23% of patients die within 1 year.^15–17 Mortality rates are directly related to type of stroke, with 80% of patients dying after an intracerebral hemorrhage, 50% after a subarachnoid hemorrhage, and 30% after occlusion of a major vessel by a thrombus. Death from stroke may not be immediate (sudden death) but rather may occur hours, days, or even weeks after the initial stroke episode.^15–17

If the victim survives, it is highly likely that a neurologic deficit or disability of varying degree and duration will remain. Of those who survive the stroke, 10% recover with no impairment, 50% have a mild residual disability, 15% to 30% are disabled and require special services, and 10% to 20% require institutionalization. Approximately 50% of those who survive the acute period (the first 6 months) are alive 7 years later.^15–17

The type of residual deficit that results from a stroke is directly dependent on the size and location of the infarct or hemorrhage. Deficits include unilateral paralysis, numbness, sensory impairment, dysphasia, blindness, diplopia, dizziness, and dysarthria. Return of function is unpredictable and usually takes place slowly, over several months. Even with improvement, patients frequently are left with some permanent residual problem, such as difficulty in walking, using the hands, performing skilled acts, or speaking. Dementia also may be an outcome of stroke.^15–19

Signs and Symptoms

Familiarity with the warning signs and symptoms and the phases of stroke can lead to appropriate action that may be lifesaving. Four events associated with stroke are (1) the transient ischemic attack (TIA), (2) reversible ischemic neurologic deficit (RIND), (3) stroke-in-evolution, and (4) the completed stroke. These events are defined principally by their duration.^12,13

A TIA is a “mini” stroke that is caused by a temporary disturbance in blood supply to a localized area of the brain. A TIA often is associated with numbness of the face, arm, or leg on one side of the body (hemiplegia); weakness, tingling, numbness, or speech disturbances that usually last less than 10 minutes. Most commonly, a major stroke is preceded by one or two TIAs within several days of the first attack.^15–17

A RIND is a neurologic deficit that is similar to a TIA but does not clear within 24 hours. Eventual recovery is the rule, however.^15–17

Stroke-in-evolution is a neurologic condition that is caused by occlusion or hemorrhage of a cerebral artery in which the deficit has been present for several hours and continues to worsen during a period of observation. Signs of stroke include hemiplegia, temporary loss of speech or trouble in speaking or understanding speech, temporary dimness or loss of vision, particularly in one eye (may be confused with migraine), unexplained dizziness, unsteadiness, or a sudden fall.^15–17

Clinical manifestations that remain after a stroke vary in accordance with the site and size of residual brain deficits; these include language disorders, hemiplegia, and paresis, a form of paralysis that is associated with loss of sensory function and memory and weakened motor power. Box 27-3 presents the different behavioral manifestations of right-sided brain damage versus left-sided brain damage. Of note, in most patients with stroke, the intellect remains intact; however, massive left-sided stroke has been associated with cognitive decline.^15–1820

Laboratory Findings

Patients suspected of having had a stroke usually undergo a variety of laboratory tests and diagnostic imaging procedures to rule out conditions that can produce neurologic alterations, such as diabetes mellitus, uremia, abscess, tumor, acute alcoholism, drug poisoning, and extradural hemorrhage.^12,13 Such investigations often include urinalysis, blood sugar level, complete blood count, erythrocyte sedimentation rate, serologic tests for syphilis, blood cholesterol and lipid levels, chest radiographs, and electrocardiogram (ECG). Various abnormalities may be disclosed by the test results, depending on the type and severity of stroke and its causative factors. A lumbar puncture also may be ordered by the physician to check for blood or protein in the cerebrospinal fluid (CSF) and for altered CSF pressure, which would be suggestive of subarachnoid hemorrhage.^12,13 Doppler blood flow studies, EEG, cerebral angiography, CT (Figure 27-6), and MRI, including diffusion and perfusion studies of the brain, are important for determining the extent and location of arterial injury.^12–1421

FIGURE 27-6 Computed tomography (CT) scan of the brain demonstrating a cerebrovascular accident (stroke) lesion that extended from the midbrain to the temporal lobe.

Prevention

The first aspect of stroke management is preven/>