First Seizure in Adulthood, Diagnosis and Treatment

[DrNour/Nour]

First Seizure in Adulthood, Diagnosis and Treatment



Introduction








Many diseases can cause paroxysmal clinical events. The correct diagnosis of the paroxysmal event is necessary to provide correct treatment. If the event is an epileptic seizure, the seizure type and associated clinical, electroencephalographic (EEG), and neuroimaging findings assist in determining the risk of seizure recurrence and the possible need to begin anticonvulsant therapy. Yet, the correct diagnosis is often missed.



http://img.medscape.com/pi/emed/ckb/neurology/1134815-1183857-1186214-1737378tn.jpg (javascript:showcontent('active','hiddenlayerd26e1 583');)An EEG recording of a temporal lobe seizure. The ictal EEG pattern is shown in the rectangular areas.


http://img.medscape.com/pi/emed/ckb/neurology/1134815-1183857-1186214-1737378.jpgAn EEG recording of a temporal lobe seizure. The ictal EEG pattern is shown in the rectangular areas.





http://img.medscape.com/pi/emed/ckb/neurology/1134815-1183857-1186214-1737379tn.jpg (javascript:showcontent('active','hiddenlayerd26e1 598');)An EEG recording from a patient with primary generalized epilepsy. A burst of bilateral spike and wave discharge is shown in the rectangular area.



http://img.medscape.com/pi/emed/ckb/neurology/1134815-1183857-1186214-1737379.bmpAn EEG recording from a patient with primary generalized epilepsy. A burst of bilateral spike and wave discharge is shown in the rectangular area.





http://img.medscape.com/pi/emed/ckb/neurology/1134815-1183857-1186214-1737382tn.jpg (javascript:showcontent('active','hiddenlayerd26e1 613');)An EEG recording of a seizure from a subdural array in a patient evaluated for epilepsy surgery. The subdural electrodes record from the left anterior temporal (LAT), left middle temporal (LMT), and left posterior temporal (LPT) regions. The EEG seizure pattern is seen best in bipolar EEG channels LAT 3-4and LMT 3-4 (rectangular areas).


http://img.medscape.com/pi/emed/ckb/neurology/1134815-1183857-1186214-1737382.bmpAn EEG recording of a seizure from a subdural array in a patient evaluated for epilepsy surgery. The subdural electrodes record from the left anterior temporal (LAT), left middle temporal (LMT), and left posterior temporal (LPT) regions. The EEG seizure pattern is seen best in bipolar EEG channels LAT 3-4and LMT 3-4 (rectangular areas).



In 1998, Scheepers et al reported 49 patients with an incorrect diagnosis and 26 patients with an uncertain diagnosis among 214 patients with a diagnosis of epilepsy (http://emedicine.medscape.com/article/1186872-overview).[/URL] In addition, about 30% of patients seen at epilepsy centers for refractory seizures turn out to have been misdiagnosed and do not have seizures.
This article focuses on 2 related questions:



Is the spell an epileptic seizure?
If the event is epileptic, is it likely to recur?


Thus, the stepwise approach should be:


Is it a seizure?
Is it epilepsy?
What kind of epilepsy?
What is the cause?


This article describes the common clinical features of patients with a first seizure, risk factors for seizure recurrence, and a general approach to management.




Pathophysiology



The definitions of the following terms come from the [URL="http://www.ilae-epilepsy.org/"]International League Against Epilepsy (ILAE) (javascript:showcontent('active','references');) Guidelines.3 (javascript:showcontent('active','references');),4 (javascript:showcontent('active','references');),5 (javascript:showcontent('active','references');)
An epileptic seizure is a clinical event presumed to result from an abnormal and excessive neuronal discharge. The clinical symptoms are paroxysmal and may include impaired consciousness and motor, sensory, autonomic, or psychic events perceived by the subject or an observer.
Epilepsy occurs when 2 or more epileptic seizures occur unprovoked by any immediately identifiable cause. The seizures must occur more than 24 hours apart. In epidemiologic studies, an episode of status epilepticus (http://emedicine.medscape.com/article/1164462-overview) is considered a single seizure. Febrile seizures and neonatal seizures are excluded from this category.
Idiopathic epilepsy describes epilepsy syndromes with specific age-related onset, specific clinical and electrographic characteristics, and a presumed genetic mechanism.
Epileptic seizures are classified as cryptogenic or symptomatic. Cryptogenic seizure is a seizure of unknown etiology. This type of seizure is not associated with a prior CNS insult known to increase the risk of developing epilepsy. It does not conform to the criteria for the idiopathic or symptomatic categories. Previous studies use the term idiopathic to describe a seizure of unknown etiology. However, current ILAE guidelines discourage use of the term idiopathic to describe a seizure of unknown etiology.
Symptomatic seizure is a seizure caused by a previously known or suspected disorder of the CNS. This type of seizure is associated with a prior CNS insult known to increase the risk of developing epilepsy.
An acute symptomatic seizure is one that occurs following a recent acute disorder such as a metabolic insult, toxic insult, CNS infection, stroke, brain trauma, cerebral hemorrhage, medication toxicity, alcohol withdrawal, or drug withdrawal. An example of an acute symptomatic seizure is a seizure that occurs within 1 week of a stroke or head injury. Studies have reported that 25-30% of first seizures are acute symptomatic seizures.6 (javascript:showcontent('active','references');)
A remote symptomatic seizure is a seizure that occurs more than 1 week following a disorder that is known to increase the risk of developing epilepsy. The seizure may occur a long time after the disorder. These disorders may produce static or progressive brain lesions. An example of a remote symptomatic seizure is a seizure that first occurs 6 months following a traumatic brain injury (http://emedicine.medscape.com/article/326510-overview) or stroke (http://emedicine.medscape.com/article/793904-overview).
Seizures are also classified as provoked or unprovoked. A provoked seizure is an acute symptomatic seizure. An unprovoked seizure is a cryptogenic or a remote symptomatic seizure.


Compared with an epileptic seizure, a nonepileptic event is a clinical event that can mimic, and be mistaken for, an epileptic seizure. Examples of nonepileptic events that mimic seizures include syncope and psychogenic nonepileptic attacks (PNEAs). Syncope is caused by decreased cerebral perfusion that results mostly from a decrease in the cardiac output, which results in loss of consciousness.







Frequency



United States



In 1997, Moore-Sledge reported that the annual incidence of adult-onset seizures in the United States was 84 cases per 100,000 population and that about 6% of the US population experience a nonfebrile seizure sometime during life.7 (javascript:showcontent('active','references');) She estimated that approximately 50 out of 84 patients develop epilepsy.
International



In European studies, the incidence of first unprovoked seizures ranges from 26-70 cases per 100,000 persons. Beghi et al attributed the variability to differences in methodology and definitions.8 (javascript:showcontent('active','references');) The rates were similar in different geographic areas despite technical differences in the studies.

Mortality/Morbidity



In a recent study, individuals with a first acute symptomatic seizure were found to be significantly more likely to die in the first 30 days after the seizure compared with those with a first unprovoked seizure; however, the risk of 10-year mortality did not differ.9 (javascript:showcontent('active','references');) Also, the risk for subsequent unprovoked seizure was 80% lower in the group with first acute symptomatic seizure compared with those with first unprovoked seizure.

Race



Racial differences have not been studied.

Sex



Most authors report a small-to-moderate preponderance of men in their studies of first seizures in adults.10 (javascript:showcontent('active','references');),1 1 (javascript:showcontent('active','references');),1 2 (javascript:showcontent('active','references');),1 3 (javascript:showcontent('active','references');)
In 1986, Annegers et al found a slight overall preponderance of women.14 (javascript:showcontent('active','references');) Their etiologic categories were neurologic deficit from birth, remote symptomatic, and no known prior etiology. They identified a preponderance of men in the group with neurologic deficit from birth, no sex preponderance in the group with remote symptomatic seizures, and a slight preponderance of women in the group with no known prior etiology. These authors did not determine if these sexual differences were statistically significant.
Among patients who had an initial generalized tonic-clonic seizure, Bora et al found that only 45.5% were men.15 (javascript:showcontent('active','references');) Patients with partial seizures and structural lesions proven on CT scan were excluded from this study.

Age



The incidence rate of epilepsy is age-related, with highest incidence in very young and very old groups. The incidence rate in children younger than 1 year is 100-233 per 100,000. The rate decreases in patients aged 20-60 years to 30-40 cases per 100,000. The rate increases to 100-170 cases per 100,000 in patients older than 65 years.16 (javascript:showcontent('active','references');)







Clinical



History



History remains the key in obtaining a correct diagnosis in patients with first seizure in adulthood. The detailed description of the actual episode in question is particularly important. The description should be obtained separately from the patient and from a caregiver who has witnessed the event. The patient may be able to report a warning or aura and the feeling after the seizure. The presence of an aura, by definition, makes the diagnosis of a localization-related epilepsy because auras are “simple partial” seizures with subjective symptoms. However, not every warning symptom is an aura.

Generally speaking, in order to be considered auras, symptoms should be brief (seconds) and followed, at least some of the time, by more definite seizure. Auras widely vary but tend to be stereotyped in a given patient. Some (eg, deja-vu, fear, epigastric sensation, lateralized somatosensory or visual phenomena) are very specific and even localizing; others are not (eg, indescribable sensation, whole body sensations, other vague symptoms like dizziness). The patient may not be able to describe the symptoms during the seizure, which speaks to loss of awareness, but says that the “next thing I know is coming to.” The caregivers or witnesses should then describe what they observe; having the caregivers mimic the types of movements or behaviors they see during the attacks may be helpful. Occasionally, the best witnesses are not present; this may require a telephone call.

The following information should be obtained in the history:




Patient's age should be recorded.
If a family history of seizures is noted, the clinical epilepsy syndrome of the affected family member should be determined.
Ask about a history of any previous provoked seizure.
Determine if the first seizure was status epilepticus.
Ask the time of day of the seizure occurrence.
History of postictal confusion, incontinence, and occurrence out of sleep.
Consider other paroxysmal neurologic events and identify seizure mimics, such as syncope (http://emedicine.medscape.com/article/811669-overview), transient ischemic attack (http://emedicine.medscape.com/article/794281-overview), transient global amnesia, migraine, sleep disorder, movement disorder, and vertigo.
In syncope, several historical features can be helpful. When an accurate description is missing (eg, unwitnessed event), the distinction between syncope and seizures can be difficult because it is based on history alone; several symptoms are helpful in aiding the diagnosis.17 (javascript:showcontent('active','references');),1 8 (javascript:showcontent('active','references');) These include the circumstances of the attacks, because the most common mechanism for syncope (vasovagal response) is typically triggered by known precipitants (eg, pain such as inflicted by medical procedures, emotions, cough, micturition, hot environment, prolonged standing, exercise).
Other historical features that favor syncope include “presyncopal” prodromes (eg, vertigo, dizziness, lightheadedness, chest pain, nausea), as well as age and a history of cardiovascular disease. Historical features that favor seizures include tongue biting, head turning, posturing, urinary incontinence, cyanosis, prodromal deja-vu, and postictal confusion.17 (javascript:showcontent('active','references');),1 8 (javascript:showcontent('active','references');) A point system using most of these features was designed, with a reported 94% sensitivity and specificity for the diagnosis of seizures.17 (javascript:showcontent('active','references');)
Psychogenic nonepileptic attacks (PNEAs) are the most common nonepileptic events seen in referral epilepsy centers but should only be considered in the setting of recurrent episodes.19 (javascript:showcontent('active','references');)
Seek a possible etiology (see Causes (http://emedicine.medscape.com/article/1186214-overview#ClinicalCauses)).


Physical




The neurologic examination should be directed at finding clinical evidence of a focal brain lesion.
A general physical examination should be performed to exclude a nonneurologic cause of the seizure.7 (javascript:showcontent('active','references');)
The examiner should pay attention to presence of signs traumatic injuries to any part of the body, especially tongue bite, which is highly specific in epileptic seizures.20 (javascript:showcontent('active','references');),2 1 (javascript:showcontent('active','references');)








Causes




Causes of epilepsy

Prenatal, perinatal, or postnatal complications of pregnancy and delivery
Febrile seizure: Distinguish a complex febrile seizure from a simple febrile seizure.
Cerebrovascular disease such as cerebral infarction, cerebral hemorrhage, and venous thrombosis
Head trauma: Head trauma is more significant when it occurs with loss of consciousness lasting longer than 30 minutes, posttraumatic amnesia lasting longer than 30 minutes, focal neurologic findings, or neuroimaging findings suggesting a structural brain injury.
CNS infections such as meningitis or encephalitis
Neurodegenerative diseases
Autoimmune disease
Brain neoplasm
Genetic diseases
Drug intoxication, drug withdrawal, or alcohol withdrawal
Metabolic medical disorders such as uremia, hypoglycemia, hyponatremia, and hypocalcemia

The wrong diagnosis of epilepsy is common; 20-30% of cases seen at epilepsy centers are misdiagnosed.19 (javascript:showcontent('active','references');),2 2 (javascript:showcontent('active','references');)

Convulsive syncope: Decreased cardiac output causes reduced cerebral perfusion with loss of consciousness and convulsive motor activity. Scheepers et al reported that cardiovascular disease was the most common diagnosis among patients whose conditions were initially misdiagnosed as epilepsy.1 (javascript:showcontent('active','references');) Using a comprehensive battery of cardiovascular tests in a population of patients diagnosed with epilepsy, Zaidi et al reported alternative diagnoses in 41%.23 (javascript:showcontent('active','references');)
Transient ischemic attack
Migraine
Sleep disorders, parasomnias, non-REM parasomnias (eg, night terrors, sleepwalking, and confusional arousals), REM behavior disorder, cataplexy (part of the narcolepsy tetrad, consisting of an abrupt loss of tone), hypnic jerks (ie, benign myoclonic jerks)
Paroxysmal movement disorders, including acute dystonic reactions, hemifacial spasms, and nonepileptic myoclonus
Transient global amnesia
Paroxysmal vertigo
Panic attacks
PNEAs: These are the most common conditions at epilepsy monitoring units. They comprise more than 90% of misdiagnosed adult cases and comprise more than 50% of cases in chidren.22 (javascript:showcontent('active','references');)
Malingering

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Differential Diagnoses



Cardioembolic Stroke (http://emedicine.medscape.com/article/1160370-overview)

Hemifacial Spasm (http://emedicine.medscape.com/article/1170722-overview)

Chorea Gravidarum (http://emedicine.medscape.com/article/1149725-overview)

Huntington Disease (http://emedicine.medscape.com/article/1150165-overview)
Chorea in Adults (http://emedicine.medscape.com/article/1149854-overview)
Hyperammonemia (http://emedicine.medscape.com/article/944996-overview)

Complex Partial Seizures (http://emedicine.medscape.com/article/1183962-overview)

Migraine Variants (http://emedicine.medscape.com/article/1142731-overview)
Epilepsia Partialis Continua (http://emedicine.medscape.com/article/1186731-overview)

Narcolepsy (http://emedicine.medscape.com/article/1188433-overview)
Epilepsy, Juvenile Myoclonic (http://emedicine.medscape.com/article/1185061-overview)

Posttraumatic Epilepsy (http://emedicine.medscape.com/article/1184178-overview)
Epileptiform Discharges (http://emedicine.medscape.com/article/1138880-overview)

Psychogenic Nonepileptic Seizures (http://emedicine.medscape.com/article/1184694-overview)

Essential Tremor (http://emedicine.medscape.com/article/1150290-overview)

Reflex Epilepsy (http://emedicine.medscape.com/article/1187259-overview)


First Seizure: Pediatric Perspective (http://emedicine.medscape.com/article/1179097-overview)


REM Sleep Behavior Disorder (http://emedicine.medscape.com/article/1188651-overview)
Frontal Lobe Epilepsy (http://emedicine.medscape.com/article/1184076-overview)
Restless Legs Syndrome (http://emedicine.medscape.com/article/1188327-overview)


Other Problems to Be Considered









Workup



Laboratory Studies




Metabolic screening for uremia, hypoglycemia, drug intoxications, and electrolyte disorders should be conducted for patients with first seizure who present to the emergency department.24 (javascript:showcontent('active','references');)
Other laboratory investigations may be indicated for specific clinical situations.


Imaging Studies




Neuroimaging should be performed because discovery of an epileptogenic lesion can have an impact on the diagnosis, prognosis, and treatment of new-onset seizures.
MRI improves diagnostic accuracy. Using clinical and EEG data alone, King et al were able to identify 23% of patients as having primary generalized epilepsy, 54% as having partial epilepsy, and 23% as having unclassified seizures.13 (javascript:showcontent('active','references');) Using clinical, EEG, and MRI data, they were able to determine that 23% of patients had primary generalized epilepsy, 58% had partial epilepsy, and 19% had unclassified seizures.
CT scanning might miss surgically remedial brain lesions that would otherwise be detected by MRI. King et al found that CT scanning detected only 12 of the 28 brain lesions that were detected by MRI; 7 of the missed lesions were brain tumors.13 (javascript:showcontent('active','references');)
Neuroimaging is unlikely to detect brain lesions in patients with clinical and EEG features of idiopathic generalized epilepsy or benign rolandic epilepsy. King et al found that MRI did not detect any brain lesions in 49 patients with clinical and EEG features of idiopathic generalized epilepsy or in 11 patients with benign rolandic epilepsy.13 (javascript:showcontent('active','references');)
Chadwick and Smith concluded that plausible arguments may be made for obtaining routine early CT scanning and reserving MRI for patients with epilepsy whose seizures are not controlled by antiepileptic drugs.25 (javascript:showcontent('active','references');)


Other Tests




EEG should be performed within 24 hours of the seizure because it is significantly more sensitive when obtained during that period.13 (javascript:showcontent('active','references');) If the routine EEG findings are normal, a sleep-deprived EEG should be performed.
Standard EEG detects epileptiform discharges in 29% of patients. Standard EEG combined with sleep-deprived EEG shows epileptiform discharges in 48% of patients.10 (javascript:showcontent('active','references');)
EEG significantly improves diagnostic accuracy in patients with a first seizure. Using clinical data alone, King et al were able to determine that 8% of patients had primary generalized epilepsy, 39% had partial epilepsy, and 53% had unclassified seizures.13 (javascript:showcontent('active','references');) Using clinical and EEG data, they were able to determine that 23% of patients had primary generalized epilepsy, 53% had partial epilepsy, and 23% had unclassified seizures.
Simpson et al described a case in which the placement of an insertable loop recorder, an important new tool in the diagnostic evaluation of patients with syncope, led to an unexpected diagnosis of a seizure.26 (javascript:showcontent('active','references');) Whenever cardiovascular causes are considered as the cause of a patient's spells but cannot be proven with conventional investigations, the use of the insertable loop recorder should be considered.
Schreiner and Pohlman-Eden studied the value of an EEG taken within 48 hours of the first seizure in an adult.27 (javascript:showcontent('active','references');) They found that 38% of patients without seizure recurrence had normal EEGs, while only 10.2% of patients with seizure recurrence had normal EEGs. Focal epileptiform activities were found significantly more frequently (26.5% vs 13%) in patients with seizure recurrence than in patients without seizure recurrence.
Unfortunately, although EEG can be helpful, it is often harmful because normal EEGs are frequently overread as epileptiform, leading to the misdiagnosis of seizures.22 (javascript:showcontent('active','references');),2 8 (javascript:showcontent('active','references');) The tendency to overread normal EEGs is common and has numerous causes.29 (javascript:showcontent('active','references');) The most common reason for misdiagnosis is that the history is not suggestive of seizures but the entire diagnosis is essentially based on the EEG.

[DrNour/Nour]

Treatment






Medical Care




Many patients who have a single seizure do not require anticonvulsant therapy. The physician and patient or family should decide jointly whether to institute anticonvulsant therapy after a single seizure. This decision is based on a discussion of the risk of seizure recurrence, the effectiveness of anticonvulsant treatment, and the adverse medical and socioeconomic effects of anticonvulsant treatment.
A first seizure provoked by an acute brain insult is unlikely to recur (3-10%), whereas a first unprovoked seizure has a recurrence risk of 30-50% over the next 2 years. Even among symptomatic seizures, the recurrence rate differs according to the underlying cause. Seizures associated with reversible metabolic or toxic disturbances are associated with a minor risk of subsequent epilepsy (£ 3% based on large case series). Seizures provoked by disorders that cause permanent damage to the brain, such as brain abscess (http://emedicine.medscape.com/article/781021-overview), have a higher risk of recurrence (³ 10%).6 (javascript:showcontent('active','references');)
Among medically untreated patients in one study, the cumulative 2-year risk of seizure recurrence was 51%.30 (javascript:showcontent('active','references');) Hauser et al found that variability in the reported risks of seizure recurrence may have been due to the following:31 (javascript:showcontent('active','references');)

Variations in patient populations: Some studies reflect the risk in referral populations; other studies reflect the risk in a more general patient population.
Variations in the specificity and sensitivity of case definitions
Misclassification of cases: Hauser et al found that 74% of the patient cohort required exclusion because of a previous unprovoked seizure.16 (javascript:showcontent('active','references');)
Variations in time of ascertainment
Biases from retrospective study design
Confounding effect of anticonvulsant treatment: Many of the previous studies included patients who received anticonvulsant therapy after their first seizure.

Risk factors for recurrent seizures include the following:

Age younger than 16 years: Musicco et al found that children younger than 16 years had almost double the risk of recurrent seizures as adolescents and adults aged 16-60 years.30 (javascript:showcontent('active','references');)
Remote symptomatic seizure:14 (javascript:showcontent('active','references');),3 1 (javascript:showcontent('active','references');),3 2 (javascript:showcontent('active','references');) In the case of seizures after a first stroke, Labovitz et al found that lesion location and stroke subtype are strong predictors of early seizure risk, and early seizures are a predictor of recurrent seizures.33 (javascript:showcontent('active','references');)
Seizures occurring between midnight and 8:59 am12 (javascript:showcontent('active','references');),3 4 (javascript:showcontent('active','references');),1 5 (javascript:showcontent('active','references');)
Prior provoked seizures31 (javascript:showcontent('active','references');)
Previous febrile seizure6 (javascript:showcontent('active','references');)
Family history of epilepsy;6 (javascript:showcontent('active','references');) remote symptomatic seizure in a patient whose sibling is affected with epilepsy
Status epilepticus or multiple seizures within 24 hours as the initial remote symptomatic seizure31 (javascript:showcontent('active','references');)
Partial seizures14 (javascript:showcontent('active','references');),3 2 (javascript:showcontent('active','references');)
Todd paralysis in patients with a remote symptomatic seizure31 (javascript:showcontent('active','references');)
History of neurologic deficit from birth such as cerebral palsy or mental retardation14 (javascript:showcontent('active','references');)
Abnormal examination findings in patients without a remote symptomatic seizure14 (javascript:showcontent('active','references');),3 5 (javascript:showcontent('active','references');)
CT scan that shows a brain tumor12 (javascript:showcontent('active','references');)
EEG that shows epileptiform discharges

In patients with a first seizure and no known etiology, van Donselaar obtained a routine EEG in all cases and a second sleep-deprived EEG if the first EEG did not show epileptiform discharges.10 (javascript:showcontent('active','references');) His pooled results showed the following 2-year cumulative risks of seizure recurrence: in patients with epileptiform discharges, 83%; in patients with nonepileptiform abnormalities, 41%; and in patients with normal EEGs, 12%.
In 1997, Beghi et al found that epileptiform discharges were associated with a 1.5- to 3-fold increase in the risk of seizure recurrence.8 (javascript:showcontent('active','references');)
In 1993, Musicco et al found that epileptiform discharges were associated with a 1.7-fold increased seizure recurrence risk.30 (javascript:showcontent('active','references');)
Berg and Shinnar found that epileptiform discharges were associated with a 2-fold increased seizure recurrence risk.32 (javascript:showcontent('active','references');)
In 1990, Hauser et al found that generalized spike and wave increased the risk of recurrent seizure in patients with no known etiology.31 (javascript:showcontent('active','references');)
In 1997, Beghi et al found that an abnormal EEG finding and the presence of an underlying etiology (remote symptomatic) are the most consistent predictors of recurrence.8 (javascript:showcontent('active','references');)


Immediate anticonvulsant treatment reduces the likelihood of a second seizure by half.30 (javascript:showcontent('active','references');) According to a 1993 report, Chandra found that valproate treatment reduced seizure recurrence rates from 63% to 4.3%.36 (javascript:showcontent('active','references');)
Immediate anticonvulsant therapy does not affect the long-term prognosis for achieving 1-year or 2-year seizure-free remission and exposes many patients who would never have a recurrent seizure to anticonvulsant side effects.11 (javascript:showcontent('active','references');)
The general consensus is that anticonvulsant treatment is needed after 2 seizures. The decision to provide anticonvulsant treatment after one seizure should be individualized.

Two situations that are often encountered in clinical practice and should be distinguished are a first seizure and new-onset epilepsy with more than one unprovoked seizure. Berg and Shinnar emphasized the need to distinguish between these two entities in clinical studies.32 (javascript:showcontent('active','references');)
Seizure recurrence risk is substantially higher after 2 or more unprovoked seizures than after just one.31 (javascript:showcontent('active','references');)



Medication



The chosen antiepileptic drug should have high efficacy, long term safety, good tolerability, and low interaction potential and should allow a good quality of life, especially because half of all patients never have another seizure without treatment.6 (javascript:showcontent('active','references');) These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.37 (javascript:showcontent('active','references');)
The accepted principle is that one should begin with monotherapy. All newer (second-generation) agents are acceptable choices and are likely just as effective as older agents. A recent American Academy of Neurology (AAN) evidence-based guideline recommended lamotrigine, oxcarbazepine, topiramate, and gabapentin as appropriate for initial monotherapy; however, this did not include newer antiepileptic drugs, such as levetiracetam and pregabalin.
In a 1995 report, phenytoin, carbamazepine, valproate, and phenobarbital were equally effective in treating newly diagnosed epilepsy; phenobarbital had more adverse effects.38 (javascript:showcontent('active','references');) Others agree that barbiturates should be avoided because of neurotoxic and cognitive side effects.6 (javascript:showcontent('active','references');)

The SANAD study compared carbamazepine, gabapentin, lamotrigine, oxcarbazepine, and topiramate for treatment of partial seizures.39 (javascript:showcontent('active','references');) The study reported that lamotrigine was significantly better in terms of time to treatment failure than the current standard treatment, carbamazepine, and the newer drugs gabapentin and topiramate. For time to 12-month remission from seizures, carbamazepine was not significantly advantageous compared with lamotrigine. Lamotrigine also has the lowest incidence of treatment failure and has better outcome than all drugs except oxcarbazepine.

The same SANAD study compared valproate, lamotrigine, or topiramate for generalized and unclassifiable epilepsy seizures.40 (javascript:showcontent('active','references');) The study reported that valproate is the drug of choice and is better tolerated than topiramate.

Another study compared 8 antiepileptic drugs used in 20 randomized trials. In patients with partial seizures, results favor carbamazepine, oxcarbazepine and lamotrigine. For generalized tonic-clonic seizures, results favor valproate and phenytoin.41 (javascript:showcontent('active','references');)

Regarding sodium valproate, the LEAD study group recommended that sodium valproate not be used as a first-line drug in the treatment of epilepsy for women of child-bearing age because of its side effects.42 (javascript:showcontent('active','references');) Overall the newer antiepileptic drugs appear safer and better tolerated; however, they have not been used for as long or in as many patients as the older drugs. None of the common side effects of the older drugs (eg, gum hyperplasia, neuropathy) have been identified; however, ruling out potential new problems with long-term use of the newer antiepileptic drugs is difficult. Head-to-head studies have demonstrated favorable side effect profiles for gabapentin when compared with carbamazepine, and for oxcarbazepine and lamotrigine when compared with both phenytoin and carbamazepine.

All newer antiepileptic drugs, although "officially" approved as adjunctive therapy, are acceptable options for monotherapy (off-label use).

Privitera et al found topiramate 100 mg/d is as effective as therapeutic doses of carbamazepine and sodium valproate and has the fewest discontinuations due to adverse events.

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