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-Seizures ~Special Populations


Here's another article that needs to be summarized both or children and adults!!  Of particular concern is other medications and OTC things that can cause seizures in themslves!  Finding several excellent articles describing that a phyisician SHOULD do from evaluating patients for certain symptoms, to determing depression and long  term care!!  Source:  www.postgradmed.com
Here's another article that needs to be summarized both for children and adults!!  Of particular concern  is other medications and OTC things that can cause seizures in themslves!  See "Patients taking other  medications" towards bottom.
Seizures in special populations
Children, the elderly, and patients with coexistent medical illness
Joseph F. Hulihan, MD
This is the fourth of four articles on seizure management
What are the features of the most common pediatric epilepsy syndromes?
Which pharmacokinetic factors affect anticonvulsant dosing in patients with kidney or liver disease?
How do the causes and treatment of epilepsy differ in the elderly?
Which medications commonly provoke epileptic seizures?
Dr Hulihan answers these and more questions about managing seizures in special populations.
Certain groups of patients present unique challenges in the management of epilepsy. Children,  the elderly, and those with coexistent medical illness may differ from healthy young adults in  predominant seizure types, appropriate antiepileptic drug therapy, and prognosis for seizure remission.
Interestingly, although children and the elderly are discussed here as special patient populations,  they also represent the ages when seizures are most likely to occur. The incidence of epilepsy is high during the first year of life, then decreases until after age 60, when the incidence again
begins to rise (1). Epileptic seizures are more likely to occur in individuals 75 years of age or older than in children under 10 years of age (2). In patients over age 60, concurrent medical illness or the use of medications in addition to anticonvulsants can complicate the management of seizures.
This article reviews some of the most common epilepsy management issues that are likely to confront physicians whose seizure patients include children, older adults, and patients with coexistent medical illness.
Seizures in children
It is important to the management of pediatric epilepsy to appreciate that seizures are a symptom of an underlying epilepsy syndrome (3,4.) While not all patients with seizures can be assigned to one of these syndromes, recognition of the concept of epilepsy syndromes and awareness of the
more common examples can allow physicians to refine patient management. Epilepsy diagnosis and treatment are likely to move toward a more disease-based approach as we gain information about the physiology and genetics of the various forms (5).
The following discussion of the common problems in pediatric epilepsy, from febrile seizures to Lennox-Gastaut syndrome, represents just such an approach to epilepsy diagnosis and therapy.
Febrile seizures
Febrile seizures occur in 3% to 5% of children between 6 months and 5 years of age and are the most common form of seizures in infancy (5). Half occur between 12 and 24 months of age, with a peak between 18 and 24 months (6).
Febrile seizures recur in one third of patients, and half of these experience a third seizure. Age at occurrence of the first febrile seizure is the most important predictor of recurrence (6). An infant who is under 1 year of age at first febrile seizure has a 50% chance of recurrence, whereas a child
over 3 years of age has a 20% risk. Subtypes of febrile seizures are listed in table 1.
Table 1. Subtypes of febrile seizures 
    Simple febrile seizures (all of the following):
    Single seizure
    Duration less than 15 min
    No focal features
Complex febrile seizures (one or more of the following):
    More than one seizure in 24 hr
    Duration greater than 15 min
    Focal motor features
    Abnormal neurologic status
    Afebrile seizures in a parent or sibling
Epilepsy, with seizures occurring independent of fever, develops in 1% to 10% of children with a history of febrile seizures (7). The condition is most likely to develop in those who have experienced complex febrile seizures (see table 1). Epilepsy develops in 6% of children with two or more features of complex febrile seizures, compared with 0.9% of children with none of these features (6).
Long-term use of anticonvulsants rarely, if ever, needs to be instituted after a single, simple febrile seizure. Repetitive or prolonged febrile convulsions often can be aborted with rectal benzodiazepines, which may also be used when a fever occurs in children at risk for development of febrile seizures. Long-term use of phenobarbital may prevent recurrent
febrile seizures but may be associated with adverse cognitive effects (8). Parents should be involved in decisions about use of long-term anticonvulsant therapy for complex febrile seizures.
Absence-seizure disorders
Absence seizures consist of brief episodes of behavior arrest and staring, followed by a rapid return to a normal level of awareness. Motor manifestations are most often minimal; if present, they consist of slight twitches of the extremities or facial muscles. Rarely, more complex
automatisms may occur (3). An electroencephalogram (EEG) recorded during such seizures shows a characteristic 3-Hz spike-wave pattern.
Absence seizures respond to treatment with either ethosuximide (Zarontin) or valproic acid (Depa kene, Depakote). The decision about which drug is appropriate may be influenced by the particular epilepsy syndrome in which the seizures occur.
Childhood absence epilepsy is a disorder that typically begins between the ages of 4 and 8 years.  Affected children are most often neurologically normal and are less prone to experience generalized tonic-clonic seizures than children with other absence-seizure disorders. The usual drug of choice is ethosuximide. Seizures respond equally well to valproic acid, but the potential for hepatotoxicity in younger children is a concern.
The prognosis for childhood absence epilepsy is a matter of debate. Seizures respond to anticonvulsant medication in 80% to 95% of patients, and seizures usually remit by midadolescence. Patients often have a family history of seizures, but the genetics of childhood absence epilepsy have not been precisely characterized (6).
Juvenile absence epilepsy has a later onset, between 10 and 17 years of age. Generalized tonic-clonic seizures occur in 60% to 80% of patients. Valproic acid is generally considered the drug of choice, for two reasons: It effectively treats both absence and generalized tonic-clonic seizures, and the potential side effect of hepatotoxicity is not as much of a concern in the age-group affected by juvenile absence epilepsy as in younger children.
Juvenile myoclonic epilepsy is characterized by brief, rapid jerks of the shoulders and arms, a feature termed myoclonus. Most patients also have generalized tonic-clonic seizures, and many also suffer absence seizures. Age at onset is typically between 10 and 17 years. Myoclonus and seizures may be precipitated by sleep deprivation or alcohol use.
It is important to question patients about a history of myoclonus or prior absence seizures when they present after a generalized tonic-clonic seizure, because juvenile myoclonic epilepsy requires lifelong treatment with anticonvulsants. While the medication of choice for this disorder is valproic acid, adjunctive or alternative anticonvulsants are sometimes required. In some families with this disorder, a linkage has been shown to the short arm of chromosome 6 (5).

Benign focal epilepsies of childhood
Benign rolandic epilepsy, or benign childhood epilepsy with centrotemporal spikes, is characterized by focal seizures with sensorimotor symptoms most commonly affecting the face and oropharynx, although at times with secondary generalization to a tonic-clonic seizure. The most common epilepsy of childhood, it occurs in children who are otherwise neurologically normal.
Seizures may be predominantly or exclusively nocturnal. The characteristic EEG pattern of this disorder can assist in diagnosis in a child who presents with a focal seizure. The same EEG pattern has been found in many first degree relatives of patients with this disorder, indicating a strong hereditary component. It is possible that the EEG pattern is transmitted as an autosomal dominant trait with incomplete penetranceof the seizure phenotype (9). Seizures are responsive to a number of anticonvulsants, but carbamazepine (Tegretol) is the drug of choice in most instances. Remission is virtually universal by midadolescence.
Benign occipital epilepsy, or childhood epilepsy with occipital paroxysms, is a less common idiopathic focal epilepsy that occurs in childhood. Seizures originate in the occipital lobe and, as in rolandic epilepsy, may generalize to a tonic-clonic seizure. Severe pulsatile headaches are common in the postictal period, and in instances where convulsions are absent or unwitnessed, this disorder may mimic childhood migraine.
Seizures are responsive to drugs appropriate for partial epilepsy (carbamazepine again being the usual drug of choice). There is also a genetic component to this disorder, since 47% of patients have a positive family history (9).
Lennox-Gastaut syndrome
In contrast to the other childhood disorders already discussed, Lennox-Gastaut syndrome is a severe condition characterized by mental retardation, multiple seizure types that respond poorly to medication, and often a characteristic EEG pattern with slow spike-and-wave discharges. Many patients are treated with three or more drugs in combination, with resultant medication toxicity. Simplification of anticonvulsant regimens, with reduction in the number of drugs used and, in particular, tapering and discontinuation of barbiturates, may reduce the number of seizures and ameliorate behavioral disturbances. More recently developed anticonvulsants that have shown promise in the treatment of this disorder are lamotrigine (Lamictal) and felbamate (Felbatol). The latter drug has been associated with a high risk of aplastic anemia and hepatic failure, but it remains a useful medication in carefully selected patients.
Another treatment that has received a good deal of attention is the ketogenic diet. Centuries ago, it was observed that starvation may result in cessation of seizures. In one of the ketogenic diet regimens, 87% of
calories come from fat, 6% from carbohydrates, and 7% from protein (10). The ketogenic diet may be effective in treating children with Lennox-Gastaut syndrome and other refractory generalized seizures (10). The most common difficulty is lack of patient compliance.
        (Seizures in the elderly see Source URL)
Anticonvulsant pharmacokinetics
The activity of an anticonvulsant drug depends on its concentration within the central nervous system. Age-related changes in liver and kidney function, in the gastrointestinal system, and in levels of circulating proteins all can affect the available levels of anticonvulsant drugs.
Hepatic function is altered in several ways as a person ages: Hepatic blood flow and liver volume are reduced and the activity of P-450 enzyme systems declines. In the kidney, renal mass is reduced and there are declines in the glomerular filtration rate and in creatinine clearance. Gastrointestinal changes, such as decreases in gastric acidity and intestinal motility, may also alter the available levels of anticonvulsants.
The major anticonvulsants--phenytoin (Dilantin), carbamazepine, and valproic acid--are all highly protein-bound. As persons age, they experience a reduction in serum albumin and an increase in alpha (1) acid glycoprotein (15). Since anticonvulsant activity depends on the amount of unbound drug, alterations in protein binding can influence medication efficacy and toxicity.
Serum drug levels, which reflect the total (bound plus unbound) drug concentrations, may be misleading when there are changes in protein-binding kinetics. Age-related decreases in albumin reduce the number of binding sites for drugs such as phenyt oin, with resultant increases in the
free fraction. Since total serum phenytoin consists mainly of roteinbound drug, the measured blood level in an older patient may be lower than it would be for a young adult taking the same dose.
Because of the reduction in metabolism, the decrease in the protein-bound fraction, and the saturation kinetics of phenytoin, older patients should receive lower initial and maintenance doses of phenytoin and relatively smaller increments in dose (in the range of 10%) (15). Use of the
30-mg phenytoin sodium capsule (Dilantin Kapseals) and the 50-mg phenytoin tablet (Dilantin Infatab) can assist in making these smaller dosage alterations.
Age-related changes in alpha (1) acid glycoprotein also affect anticonvulsant drug levels. A reactant protein, alpha (1) acid glycoprotein increases with systemic illness and in the setting of enzyme-inducing
drugs, such as phenytoin or carbamazepine. Carbamazepine and its major metabolite, carbamazepine epoxide, show increases in the protein-bound fraction as alpha (1) acid glycoprotein levels rise. This can result in elevations of the serum carbamazepine level in the absence of concomitant increases in the unbound fraction.
Because of variability in the metabolism and protein binding of carbamazepine and the other major anticonvulsant drugs, initial and maintenance doses and dosage alterations in elderly patients should
generally be smaller than in younger patients.
The factors discussed above also contribute to the propensity for elderly patients to manifest symptoms of anticonvulsant toxicity at doses lower than in younger patients.

Seizures in special medical populations
The coexistence of other medical illnesses, including liver and kidney disease, in patients with epilepsy may complicate the use of anticonvulsant drugs. In addition, certain drugs that are indicated for
treatment of coexistent disease may be epileptogenic.
 (For seizures in Patients with liver or kidney disease go to source URL)

Patients taking other medications
Certain types of medications and individual drugs have been implicated in the production or exacerbation of seizures. The most well known of these are perhaps the psychotropic drugs, in particular antidepressants and major tranquilizers.
Most of the tricyclic and nontricyclic antidepressant drugs have been associated with an increase in seizures. Tricyclic intoxication is associated with seizures, as is use of tricyclic drugs within the usual therapeutic range in about 1% of patients (18).
Of the tricyclic antidepressants, desipramine hydrochloride (Norpramin) is thought to have the lowest potential for seizure causation. Bupropion (Wellbutrin) has also been associated with precipitation of seizures (19).
Antipsychotic drugs vary in their capacity to induce seizures.
  • The potential for precipitation of seizures appears to be greater for phenothiazines than for haloperidol (Haldol), and the effect is dose-dependent (18).
  • Chlorpromazine hydrochloride (Ormazine, Thorazine), other phenothiazines, and haloperidol have been shown to activate epileptiform patterns on human EEG studies (20).
  • Clozapine (Clozaril) is also associated with seizures in a dose-dependent fashion (18).
  • Thioridazine hydrochloride (Mellaril) is less epileptogenic in EEG studies and is thought to be less likely to produce seizures clinically.
Medications used for a number of other medical conditions have been implicated in epileptic seizures. Theophylline may cause seizures, most often at toxic levels, but also when the serum level is within
the therapeutic range.
Many over-the-counter cold preparations contain potentially epileptogenic compounds.
  • Diphenhydramine hydrochloride has been shown to activate epileptiform EEG patterns and also to provoke clinical seizures.
  • Phenylpropanolamine hydrochloride, a sympathomimetic used in cold preparations and nonprescription anorectics, has been associated with seizures in nonepileptic children (16).
  • Pseudoephedrine hydrochloride and phenylephrine hydrochloride have not shown such an association and can be safely recommended to patients with epilepsy.
Several antibiotics may precipitate seizures, including penicillin, imipenem, and metronidazole (Flagyl, Protostat). The seizures associated with isoniazid (Laniazid, Nydrazid) intoxication can be reversed by intravenous administration of pyridoxine hydrochloride.
Another consideration in the use of antibiotics involves their coadministration with carbamazepine. Erythromycin and some other antibiotics can produce symptoms of toxicity by inhibiting hepatic
enzyme systems, resulting in elevation of the carbamazepine level.
Another medication of increasing importance in causation of seizures is cyclosporine (Neoral, Sandimmune).
Seizures sometimes occur after organ transplantation and, along with cerebral infarction and postoperative metabolic derangements, cyclosporine may be a causative factor.
It is rare that a medication needs to be entirely excluded from use because of the possibility of seizure  precipitation. Close patient monitoring, combined with measurement of drug levels when indicated, can allow the safe use of these medications in most instances.

Epilepsy management may need to be modified in certain patient groups. The management of epilepsy in all age-groups, and particularly in children, may be best approached from a disease-based model that recognizes specific epilepsy syndromes. Accurate diagnosis of pediatric epilepsy syndromes allows the physician to improve medication selection, estimate duration of treatment, and counsel patients and family members about aggravating factors and prognosis.
Epilepsy management in elderly patients requires knowledge of age-related changes in the metabolism and protein binding of anticonvulsants and how these changes affect use of particular antiepileptic drugs.
Concurrent medical illness, especially renal and hepatic disease, may alter drug distribution, metabolism, and excretion in some patients. In addition, a number of medications used to treat coexistent medical or psychiatric illness are associated with seizure provocation.
Knowledge of these factors can improve epilepsy management in special patient populations.
            (References - See source URL)
Dr Hulihan is director of the Comprehensive Epilepsy Center, Temple University School of Medicine, Philadelphia. Correspondence: Joseph F. Hulihan, MD, Department of Neurology, Temple University School of Medicine, 3401 N Broad St, Philadelphia, PA 19140. E-mail: hulihan@astro.ocis.temple.edu