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Deborah W. Wilbur, MD

• Hematologist/Medical Oncologist
• Private Practice
• Oncology Associates
• Cedar Rapids, Iowa

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Many clinicians have used slow tapering schedules lasting many months or even years, thinking that they would reduce the risk of recurrence. A well-designed, prospective, randomized clinical trial has provided solid data on this issue (75). There were no differences in recurrence risk at 2 years between the groups with short and long tapering regimens. This well-designed study should finally settle this long-standing controversy, although specific drugs, such as barbiturates and benzodiazepines, might require slightly longer tapering periods. Note that a long tapering period will not alter the recurrence risk at 2 years, but may delay the recurrence and, thus, tends to prolong the period of uncertainty. Duration of Seizure-Free Interval Prior to Attempting Withdrawal of Antiepileptic Drugs the chances of remaining seizure-free after medication withdrawal is similar whether a 2-year (50,53,55,65,73,74,76) or a 4-year seizure-free interval (59,63,64,68,73,76) is used. One study that evaluated seizure-free intervals of 1 or more years did find that a longer seizure-free period was associated with a slightly lower recurrence risk (76). However, the higher relapse rates were primarily observed in those who were withdrawn after 1 year. The prognosis for long-term remission appears to be primarily a function of the underlying epilepsy syndrome. Generally, the risks of medication withdrawal in this population appear similar to those seen in those with remote symptomatic epilepsy in remission on medications (51,73). It, therefore, appears reasonable to consider medication withdrawal in patients who are seizure-free following resective surgery (95,98,101). The prognostic factors for successful medication withdrawal are not well defined but appear to be different than for those who become seizure-free with medical therapy (98). In principle, one can ask, following a potentially curative procedure, why to wait more than a short seizure-free interval, such as 6 months or a year, before attempting withdrawal in this population (98). The physician should remember that while some patients may be eager to try coming off medication in the belief that they are cured (98), many may be unwilling to jeopardize their newly achieved seizure-free state. The decisions need to be individualized, based on the potential risks and benefits in each case and the personal preferences of the patient. Further, well-controlled prospective studies are needed to provide rational practice guidelines to inform the clinical decision in this setting.

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However, this association of seizure type and ictal electroencephalographic pattern was not predictive of outcome in younger patients (16,30). This view has not been universally accepted; Phillips and Sakas did not find neuroimaging or electroencephalographic findings to be predictive of outcome (29). Patients with complex partial seizures are less likely to respond to this procedure; approximately 40% achieve a significant seizure reduction. Corpus callosotomy had been used in patients with frontal lobe seizures in whom the seizure focus could not be lateralized because of very rapid spread of epileptiform activity. Clark in 2007 found that a planned palliative corpus callosotomy may help identify a resectable epileptic foci (31). Corpus callosotomy may be performed as a partial resection involving the anterior two third (in the majority of cases) or a complete section. Rahimi in 2007 concurred that in patients with secondarily generalized intractable epilepsy complete callosotomy was superior to partial callosotomy (35). Maehara and Shimizu advocate a complete callosotomy, especially in children and in adults with widespread epilepsy (36). In any event, when a complete section is considered, it should be carried out as a two-stage procedure to minimize neuropsychological complications. They found a favorable outcome, defined as a 50% reduction of seizures reported in 60% to 80% of all patients with atonic seizures and tonic seizures resulting in falls. Improvements in quality-of-life indices and social adjustment did not always coincide with reduction in seizure frequency. The length of time for which the patient had had intractable epilepsy and its deleterious effect on his or her cognitive and social function were important variables in predicting quality-of-life improvements. In a study conducted at the Cleveland Clinic, 9 of 17 patients experienced a greater than 80% reduction in their targeted seizures and 15 of 17 reported satisfaction with the surgical outcome. However, improvement in alertness and responsiveness, not necessarily reduction in seizure frequency, was most closely associated with satisfaction with surgical outcome (38). Twenty-seven had had an anterior callosotomy; eight had a complete callosotomy in two stages, and one had a posterior callosotomy. Fourteen had excellent 986 Part V: Epilepsy Surgery results (defined as more than 90% reduction in targeted seizure type), five had good results (more than 50% reduction), six had poor results (less than 50% reduction), and five showed no change.

Syndromes

• Cancer treatments, including chemotherapy and radiation
• Other medical conditions such as multiple sclerosis, spinal cord injury, or dementia
• Feeling like a victim
• Gastritis
• Poor healing of the wounds
• Ultrasound or MRI of the pelvic area.
• Ask your doctor which medicines you should still take on the day of the surgery.
• Mental status changes

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For example, a simple monopolar charge buildup, a curved dipole sheet, or a finite-thickness dipole "pancake" would all produce a single well-defined maximum. The difference recorded between two electrodes close to the source (near-field potentials) will be greater than the differential recordings from the tail of the curve. These far-field potentials (in the shaded region) are also lower in absolute amplitude. The darker areas represent the cortical mantle that is activated by an epileptic discharge, with negative and positive poles highlighted. In the middle row of illustrations, the positions of the electrodes on the scalp, relative to the discharging cortex are shown. The head also contains normal or abnormal openings that present low-resistance paths to conducted currents. The current tends to flow toward skull defects, whether physiologic (such as foramina) or acquired through trauma or surgery, and around cavities (such as the ventricles), markedly distorting the field in the region of the defect. As a result, surface potentials near these openings will be unusually high and the largest potentials can be seen at the location of the defect even when the source is several centimeters away from the defect (38,42,43). Surface Electrical Manifestations A variety of real-world considerations complicate the interpretation of surface recordings. Because the dipoles measured at the scalp ordinarily are oriented radially, scalp electrodes see primarily the positive or the negative pole. Although generators located at the apex of a gyrus lie perpendicular to the scalp. In addition, many brain areas-most notably the mesial frontal, parietal, occipital, and basal temporal cortex-are diversely oriented and lie at varying distances from surface electrodes. Hence, it is not sufficient to assume that the generator must be close to the point where the maximum potential is recorded (7). When a generator dipole is oblique or parallel to the scalp, the resulting surface potentials can lead to false localization of the potential maximum.

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Consensus guidelines: preconception counseling, management, and care of the pregnant woman with epilepsy. Studies on long-lasting consequences of prenatal exposure to anticonvulsant drugs. On major malformations and minor anomalies in the offspring of parents with epilepsy: review of the literature. Risks to the offspring of women treated with hydantoin anticonvulsants, with emphasis on the fetal hydantoin syndrome. Pattern of malformations in the children of women treated with carbamazepine during pregnancy. The differential impact of intrauterine exposure to anticonvulsant drugs and further influential factors. Maternal seizure disorder, outcome of pregnancy, and neurologic abnormalities in the children. The effects of prenatal exposure to phenytoin and other anticonvulsants on intellectual function at 4 to 8 years of age. Follow-up study on growth and neurological development of children born to epileptic mothers. Physical growth of the children of epileptic mothers: preliminary results from the prospective Helsinki study. The teratogenicity of hydantoins and barbiturates in humans, with considerations on the etiology of malformations and cerebral disturbances in the children of epileptic parents. Long-term health and neurodevelopment in children exposed to antiepileptic drugs before birth. Somatic parameters, diseases and psychomotor development in the offspring of epileptic parents. Fetal head growth retardation associated with maternal phenobarbitone/primidone and/or phenytoin therapy [letter]. Head circumference in children of epileptic mothers: contributions of drug exposure and genetic background. Psychiatric comorbidity is common among patients with epilepsy, the clinical presentation is frequently atypical, and there is often a temporal relationship with seizures.

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Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus. From traumatic brain injury to posttraumatic epilepsy: what animal models tell us about the process and treatment options. Epilepsy following cortical injury: cellular and molecular mechanisms as targets for potential prophylaxis. Recurrent seizures induced by cortical iron injection: A model of posttraumatic epilepsy. Posttraumatic epilepsy: hemorrhage, free radicals and the molecular regulation of glutamate. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the "dormant basket cell" hypothesis and its possible relevance to temporal lobe epilepsy. Progression from frontalparietal to mesial-temporal epilepsy after fluid percussion injury in the rat. A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats. Axonal sprouting in layer V pyramidal neurons of chronically injured cerebral cortex. A critical period for prevention of posttraumatic neocortical hyperexcitability in rats. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the quality standards subcommittee of the American Academy of Neurology.

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Conclusions Our experience suggests that clobazam is well tolerated and provides good seizure reduction in patients with refractory epilepsy, with 28% of patients becoming seizure free. In addition, it appears to have a good safety profile with relatively low rates of discontinuation due to adverse effects. Jurriaan Peters is Our findings need to be interpreted in the setting of data acquisition. Our study approach was retrospective, with inherent information and selection bias. Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy. Long-term use of clobazam in Lennox-Gastaut syndrome: experience in a single tertiary epilepsy center. Clobazam has equivalent efficacy to carbamazepine and phenytoin as monotherapy for childhood epilepsy. Clinical experience with clobazam: a new 1,5 benzodiazepine in the treatment of refractory epilepsy. Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. Retention rate of clobazam, topiramate and lamotrigine in children with intractable epilepsies at 1 year. Reflex seizures induced by micturition and defecation, successfully treated with clobazam and phenytoin. Clobazam: a newly approved but wellestablished drug for the treatment of intractable epilepsy syndromes. Clobazam as an adjunctive therapy in treating seizures associated with Lennox-Gastaut syndrome.

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A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Cognitive effects of topiramate gabapentin, and lamotrigine in healthy young adults. Acute mental status changes and hyperchloremic metabolic acidosis with long-term topiramate therapy. Effect of topiramate on linear growth in children with refractory complex partial seizures [abstract]. Topiramate as first-line therapy: tolerability and safety in children and adolescents [abstract]. Acute myopia and secondary angle closure glaucoma: a rare ocular syndrome in topiramate-treated patients [abstract]. Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin. Topiramate in essential tremor: pooled data from a double-blind, placebo-controlled, crossover trial [abstract]. A double-blind placebo-controlled trial of topiramate treatment for essential tremor. Oral topiramate for treatment of alcohol dependence: a randomized controlled trial. Topiramate in the treatment of binge-eating disorder associated with obesity: a randomized, placebocontrolled trial. A 6-month randomized, placebocontrolled, dose-ranging trial of topiramate for weight loss in obesity. Effect of topiramate on diabetic control and weight in diabetic patients [abstract].

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A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy. A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy. Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial. Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy. Oxcarbazepine (Trileptal) therapy results in no clinically significant changes in weight. Improved quality of life in patients with partial seizures after conversion to oxcarbazepine monotherapy. Administration of syrup or uncoated regular tablets or capsules is followed by rapid absorption and peak levels within 2 hours. The recently approved extended-release divalproex formulation does not seem to exhibit this variation after administration to healthy volunteers (36). Rectal preparations from the syrup and capsule formulations can be prepared and have been given to patients (39,40). Monitoring of unbound drug concentration may be useful when proteinbinding alterations are suspected. In the absence of inducing drugs, the half-life in adults is 13 to 16 hours (24,45), whereas in adults receiving polytherapy with inducing drugs, the average half-life is 9 hours (23).

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The degree to which these factors are predictive, however, may differ between men and women (36). Time periods for particular concern are in the first 6 months after the diagnosis of seizures (37) and within a few months to years of attaining good seizure control after a long history of refractory epilepsy (38). The risk began as early as 1 week, and continued to at least 24 weeks, at which time most trials ended. Physicians need to document the level of risk, interventions, and plans for monitoring. Antidepressants and psychotherapy are helpful, and referral to a psychiatrist is indicated. Anxiety may lead to significant distress, and the presence of anxiety in a depressed patient with epilepsy increases the risk of suicide (33). Anxiety may occur prior to (preictal), during (ictal), or after (postictal) seizure onset. Ictal anxiety may also be present, however, with frontal, cingulate, or other limbic-onset seizures. While some authors suggest that fear lateralizes to the nondominant hemisphere (41), this is not entirely clear. Postictal anxiety occurs in an estimated 45% of those with refractory partial seizures. Contributing factors include the unpredictability of seizures, psychosocial difficulties, and iatrogenic effects. Anxiety prior to epilepsy surgery is a marker of poorer postresection psychosocial adjustment, perceived memory function, and health-related quality of life. Hence, the importance of screening should be emphasized to aid in appropriate treatment and presurgical counseling.

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This fact sheet may contain references or links to statutes, regulations, or other policy materials. We encourage readers to review the specific statutes, regulations, and other interpretive materials for a full and accurate statement of their contents. For help choosing an alternate antidepressant, see our chart, Choosing and Switching Antidepressants. For help choosing an alternate antidepressant, see our chart, Choosing and Switching Antidepressants. For help choosing an alternate antidepressant, see our chart, Choosing and Switching Antidepressants. Tertiary amines (amitriptyline, clomipramine, doxepin, imipramine, trimipramine) of special concern in patients with syncope due to risk of orthostatic hypotension. Tricyclic antidepressants: amitriptyline (A, H), amoxapine (A), clomipramine (A, H), desipramine (A), doxepin (>6 mg/day [A, H]), imipramine (A, H), nortriptyline (A), protriptyline (A), trimipramine (A, H) Continued. For help choosing an alternate antidepressant, see our chart, Choosing and Switching Antidepressants. Alternatives: for allergy, nasal saline, nasal steroid, 2nd generation antihistamine. Subscribers) and algorithm, Stepwise Treatment of Hypertension (Canadian subscribers). Antiplatelet Agents and Anticoagulants Apixaban (Eliquis) in patient Lack of evidence of efficacy and with CrCl <25 mL/min. Dipyridamole, oral short-acting (A, H) More effective options available, orthostatic hypotension Consider warfarin. Avoid chronic use of doses >325 mg/d unless alternatives are not effective and patient can take gastroprotective agent. Alternatives for secondary stroke prevention: See our chart, Antiplatelets for Recurrent Ischemic Stroke. Bleeding risk Benefit may offset bleeding risk in patients with high cardiac risk. Rivaroxaban (Xarelto) in patients 75 years of age (C), and in patients with CrCl <50 mL/min.

Real Experiences: Customer Reviews on Phenytoin

Hauke, 61 years: No dosage adjustments would therefore be expected to be needed if either of these flavonoids is given with enalapril.

Agenak, 62 years: However, this too, is often not feasible in many cases, due to several factors, which include the presence of too many disparate epileptogenic zones to be handled surgically, bilaterally homologous foci, or their overlap with eloquent cortex (32).

Marus, 21 years: One study showed 30% infant lamotrigine levels compared with maternal plasma concentrations 2 weeks after delivery (53).

Norris, 40 years: Massive epileptic myoclonus implies that a bilateral jerk is large enough to create a fall, and semiologic difficulty may arise when massive myoclonic seizures result in a fall similar to tonic and atonic seizures (drop attacks).

Sulfock, 24 years: Bioavailability of sodium valproate suppositories during repeated administration at steady state in epileptic children.

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