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Ethosuximide is a succinimide anticonvulsant, used mainly in absence seizures. It is sold by Pfizer under the name Zarontin®. more...

Zoledronic acid

Adverse Effects

Central Nervous System


  • drowsiness
  • mental confusion
  • insomnia
  • nervousness
  • headache
  • euphoria
  • ataxia
  • hiccups
  • impaired concentration
  • irritability
  • hyperactivity
  • loss of taste
  • night terrors


  • paranoid psychosis
  • increased libido
  • exacerbation of depression


  • dyspepsia
  • vomiting
  • nausea
  • cramps
  • constipation
  • diarrhea
  • stomach pain
  • loss of appetite
  • weight loss
  • gingival hyperplasia
  • swelling of tongue


  • microscopic hematuria
  • vaginal bleeding


The following can occur with or without bone marrow loss:

  • pancytopenia
  • agranulocytosis
  • leukopenia
  • eosinophilia


  • urticaria
  • systemic lupus erythematosus
  • Stevens-Johnson syndrome
  • hirsutism
  • pruritic erythematous rashes


  • myopia


  • abnormal liver function

Drug Interactions

Valproates can either decrease or increase the levels of ethosuximide; However, combinations of valproates and ethosuximide had a greater Protective Index than either drug alone.

It may elevate serum phenytoin levels.


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Evaluation and management of first seizures in adults
From American Family Physician, 9/15/97 by Cynthia M. Moore-Sledge

An estimated 6 percent of the U.S. population will experience at least one afebrile seizure during their lifetime. The annual incidence of adult-onset seizures in the United States is 84 per 100,000. Of that number, 50 patients per 100,000 develop epilepsy, with males affected more often than females.[1] Risks for recurrence following a first nonfebrile seizure include evidence of a neurologic abnormality, epileptiform abnormality on electroencephalogram or a partial seizure disorder.

Seizure Classification

A seizure is defined as abnormal neurologic functioning caused by excessive neuronal activation in the cerebral cortex or the deep limbic system. Epilepsy is defined as recurrent seizures. The International League Against Epilepsy has divided seizures into three classes: generalized, partial and unclassified.[1] Generalized seizures involve neuronal activation of both hemispheres and are further divided into absence seizures, myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures and atonic seizures. Partial seizures involve neuronal activation of one part of a cerebral hemisphere. Partial seizures are further divided into simple partial seizures (consciousness is not impaired), complex partial seizures (consciousness is impaired) and partial seizures evolving to secondarily generalized seizures. Unclassified seizures defy classification as either partial or generalized because of inadequate or incomplete data. This classification system allows communication across international boundaries and establishes uniform descriptive terminology[2,3] (Table 1).

Roadblocks to an Accurate History. Because it may affect the decision to treat, it is important to determine whether this event was the first seizure the patient has experienced--and this may be difficult to determine. For example, patients may be asleep during a seizure or experience an absence seizure and, thus, be unaware that they had a seizure. Some patients, fearing the potential ramifications (such as loss of employment, driving restrictions, stigmatization, possible commitment to a lifetime of medical treatment, difficulty in obtaining health and/or life insurance), may delay or avoid obtaining medical evaluation. In others, seizures may have been falsely ascribed to hypoglycemia or abnormal behavior.[3,7,11]

Physical Examination

A careful physical and neurologic examination should be performed with attention to signs of systemic illness, dysmorphic features, needle tracks and/or sclerosed veins suggesting drug abuse, focal neurologic deficits, orthostatic blood pressure changes and cardiac murmurs, arrhythmias and bruits.

Laboratory Tests

Routine laboratory investigation, including complete blood cell count, erythrocyte sedimentation rate, blood chemistries, VDRL, skull and chest radiographs have not been found to be helpful in pinpointing the cause of a first seizure in patients who are neurologically intact at the time of evaluation. Metabolic acidosis, leucocytosis, and/or transient electroencephalographic abnormalities may occur as a result of seizure activity and, thus, some abnormalities identified may be the result of, rather than the cause of, the seizure. Most physicians, however, continue to obtain screening laboratory tests because of medico-legal concerns. Lumbar puncture is useful only in situations where, based on the history or physical findings, the physician has a strong suspicion of meningeal irritation.[3,12] The clinician should remember, however, that a pleocytosis of up to 100 cells may result from a prolonged seizure.

Electroencephalogram. The EEG is an important tool in the diagnosis of seizures. Its diagnostic yield is increased if it is obtained during the ictal state (within 24 hours of the seizure). This test is probably the most important predictor of seizure recurrence.[1,3] In one study,[10] EEGs were obtained for 165 patients presenting with idiopathic first seizures. If the standard EEG was normal, a partial sleep-deprived EEG was also obtained. If both examinations were normal, the recurrence rate at two years was only 12 percent. On the other hand, the recurrence rate increased to 83 percent if one or both EEGs showed epileptic discharges. Nonepileptiform (non-spike-wavelike) abnormalities carried a risk of recurrence of 41 percent. Focal epileptic discharges had a higher risk of recurrence than generalized epileptic discharges.

A normal interictal EEG does not eliminate the possibility of a seizure focus, nor does a normal EEG rule out a structural lesion. Using computed tomographic (CT) scans and magnetic resonance imaging (MRI), lesions were identified in 18.8 percent of patients with normal EEGs who had a history of seizures.[6] The likelihood that EEGs will provide a diagnosis may be increased with sleep deprivation.

Radiographic Studies. Controversy regarding the routine use of CT and MRI in the evaluation of all patients with a first seizure is ongoing. In a study[13] involving 148 adult patients (median age: 47 in men, 57 in women) with focally abnormal neurologic findings had abnormal scans 82 percent of the time. The incidence of abnormal scans increased with focal seizures and with age. CT findings were abnormal in 61 percent of patients with focal seizures, 27 percent of patients with partial complex seizures and 19 percent of patients with generalized seizures of all causes. Elderly patients were more likely to have an increased incidence of abnormal CT findings, most often related to cerebrovascular events and tumors.[3,13,14]

MRI has been shown to be valuable in detecting lesions that might be missed by CT scan, such as early cerebral infarct, early inflammatory lesions, low-grade tumors and some vascular lesions. MRI offers a higher diagnostic yield than CT and is preferable if it is readily available. Both CT and MRI are indicated if the patient develops intractable seizures.

Patients undergoing evaluation should be advised not to drive or operate potentially dangerous machinery until the evaluation is complete and the risk of recurrence has been determined. Some states have specific laws mandating that physicians report persons with seizures to the state division of motor vehicles (Table 5). In states without mandatory physician reporting, the patient is responsible for reporting. The physician should carefully document his or her discussion with the patient regarding increased driving risks and the patient's responsibility to inform the division of motor vehicles.[15]


The decision to treat seizures carries with it a change in the patient's lifestyle, along with driving and occupational restrictions, social stigma, economic burdens related to the cost of the medication and adverse side effects in 30 percent of patients taking anti-epileptic drugs.[12,17]

The patient's age, seizure type and daily activities, and the possible social and economic ramifications of treatment should be considered. In 16 studies, the overall risk of recurrence was estimated to be 51 percent.[18] When no risk factors are present, the risk of recurrence of idiopathic seizures is 24 percent after two years. History of a sibling with epilepsy or an abnormal EEG also increases the risk of recurrence. Patients with partial seizures and symptomatic seizures with Todd's paralysis (transient paralysis following partial epileptic seizures), or a prior seizure history also have a significantly increased risk of recurrence.[1,18,19]


Seizure classification determines medication recommendations[7] (Table 8). A randomized, comparative monotherapy trial[20] involving 243 adults revealed no differences in efficacy between phenobarbital, phenytoin (Dilantin), carbamazepine ((Tegretol) and valproic acid (Depakene) in the treatment of tonic-clonic or partial seizures with or without secondary generalization. Phenobarbital was, however, more likely to cause intolerable side effects.

The Elderly. In the elderly, changes in body fat, declining albumin concentration, decreased liver metabolism and decreased urinary clearance necessitate lower initial doses of drugs, with a slow titration.[21,22]


Remission is defined as a prolonged seizure-free interval, specified in various studies as two to five years. Patients who experience frequent generalized seizures or multiple seizure types, or who require multiple antiepileptic medications are less likely to achieve remission. Patients responding quickly to treatment are more likely to achieve remission.


Relapse may occur during treatment, during withdrawal or following withdrawal of the medication. Fifty percent of relapses occur during drug withdrawal, with 80 percent of relapses occurring during the first year.[1] The EEG does not consistently predict the risk of relapse. Patients with seizures associated with risk factors for recurrence may be considered for withdrawal after a five-year seizure-free interval. Patients with seizures without associated risk factors for recurrence may be considered for withdrawal after a two-year interval with no seizures.

Drug withdrawal should take place over two to six months, with close follow-up. Should seizures recur, the medication should be restarted at the original dosage. The patient should be advised of regulations governing the period of remission time that is required before they can be allowed to resume driving (Table 5).


The Epilepsy Information Service may be contacted by telephone at 800-642-0500 for packets of information written for both the lay public and professionals; information may also be obtained from the Epilepsy Foundation of America, 4351 Garden City Dr., Landover, MD 20785; telephone: 800-EFA-4050.


[1.] So NK. Recurrence, remission, and relapse of seizures. Cleve Clin J Med 1993;60:439-44.

[2.] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981; 22:489-501.

[3.] Pellegrino TR. An emergency department approach to first-time seizures. Emerg Med Clin North Am 1994;12:925-39.

[4.] Sander JW, Hart YM, Johnson AL, Shorvon SD. National General Practice Study of Epilepsy: newly diagnosed epileptic seizures in a general population. Lancet 1990;336:1267-71.

[5.] Annegers JF, Hauser WA, Lee JR, Rocca WA. Incidence of acute symptomatic seizures in Rochester, Minnesota, 1935-1984. Epilepsia 1995;36:327-33.

[6.] Sempere AP, Villaverde FJ, Martinez-Menendez B, Cabeza C, Pena P, Tejerina JA. First seizure in adults: a prospective study from the emergency department. Acta Neurol Scand 1992;86:134-8.

[7.] Kaplan PW, Fisher RS. Seizure disorders. In: Barker LR, Burton JR, Zieve PD, eds. Principles of ambulatory medicine. 4th ed. Baltimore: Williams & Wilkins, 1995:1187-97.

[8.] Quirk JA, Fish DR, Smith SJ, Sander JW, Shorvon SD, Allen PJ. First seizures associated with playing electronic screen games: a community-based study in Great Britain. Ann Neurol 1995;37:733-7.

[9.] Ferrie CD, De Marco P, Grunewald RA, Giannakodimos S, Panayiotopoulos CR Video game induced seizures. J Neurol Neurosurg Psychiatry 1994;57:925-31.

[10.] van Donselaar CA, Geerts AT, Schimsheimer RJ. Idiopathic first seizure in adult life: who should be treated? BMJ 1991;302:620-3.

[11.] Edmondstone WM. How do we manage the first seizure in adults? J R Coll Physicians Lond 1995; 29:289-94.

[12.] McLachlan RS. Managing the first seizure. Can Fam Physician 1993;39:885-8.

[13.] Ramirez-Lassepas, M, Cipolle RJ, Morillo LR, Gumnit RJ. Value of computed tomographic scan in evaluation of adult patients after their first seizure. Ann Neurol 1984;15:536-43.

[14.] Young AC, Costanzi JB, Mohr PD, Forbes WS. Is routine computerised axial tomography in epilepsy worth while? Lancet 1982;2(8313):1446-7.

[15.] Krumholz A, Fisher RS, Lesser RP, Hauser WA. Driving and epilepsY A review and reappraisal. JAMA 1991;265:622-6.

[16.] Stefan H, Bauer J, Feistel H, Schulemann H, Neubaur U, Wenzel B, et al. Regional cerebral blood flow during flocal seizures of temporal and fronto-central onset. Ann Neurol 1990;27:162-6.

[17.] Randomized clinical trial on the efficacy of anti-epileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial Group (FIR.S.T. Group). Neurology 1993; 43(3 Pt 1):478-83.

[18.] Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 1991;41:965-72.

[19.] Hauser WA, Rich SS, Annegers JF, Anderson VE. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology 1990;40:1163-70.

[20.] Heller AJ, Chesterman P, Elwes RD, Crawford P, Chadwick D, Johnson AL, et al. Phenobarbitone phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. J Neurol Neurosurg Psychiatry 1995;58:44-50.

[21.] Treiman DM. Current treatment strategies in selected situations in epilepsy. Epilepsia 1993;34(Suppl 5):517-23.

[22.] Swanson PD. Treatment recommendations for anti-convulsant drug therapy in the older patient. Drugs Aging 1992;2:95-102.

Each year members of a different family practice department develop articles for "Problem-Oriented Diagnosis." This series is coordinated by the Department of Family and Community Medicine at the University of Alabama at Birmingham. Guest editors of the series are T. Michael Harrington, M.D., and Myra A. Crawford, Ph.D.

CYNTHIA M. MOORE-SLEDCE, M.D. is residency director and assistant professor in the Department of Family and Community Medicine at the University of Alabama at Birmingham, where she graduated from medical school and completed a family practice residency.

Address correspondence to Cynthia M. Moore-Sledge, M.D., Department of Family and Community Medicine, University of Alabama at Birmingham, 930 S. 20th St., Birmingham AL 35294-2042.

COPYRIGHT 1997 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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