Partial epilepsies are epileptic disorders in which seizure semiology or findings on investigation disclose localized origin of seizures. In children, cortical dysplasias and low-grade neoplasms are the most commonly identified causes.
Partial epilepsies represent the most common type of adult-onset epilepsy. Most adult-onset localization-related epilepsies do not have an identifiable etiology (ie, neuroimaging studies are most often normal). When a cause is found, it can include various structural lesions (eg, traumatic scars, neoplasms, vascular malformations, strokes, neuronal heterotopias).
Obtaining a description of the seizures from the patient and any witnesses is critical. The description needs to include a description of the patient’s state of consciousness during the seizure, to determine whether the seizure is a simple or complex partial seizure (see Clinical Presentation). Further evaluation, which may include neuroimaging, is important for determining the specific disorder, in order to determine prognosis and guide therapy (see Workup).
Partial epilepsies are generally treated with antiepileptic drugs (AEDs). Nonpharmacologic treatments in certain refractory cases include surgery and dietary modification (see Treatment and Management).
Go to Epilepsy and Seizures for a general overview of this topic.
Most partial epilepsies are the result of a localized brain abnormality, even though in most patients the abnormality cannot be seen with imaging techniques.
Only a few partial epilepsies are genetic; most are lesional. Unfortunately, in the current classification, they are referred to as idiopathic. The term idiopathic is often misunderstood in this setting. While generally idiopathic means "of unknown cause," idiopathic epilepsies are not truly of unknown cause. This terminology most likely will be corrected in the upcoming classification system of the International League Against Epilepsy (ILAE). Idiopathic epilepsies are determined genetically and have no apparent structural cause, with seizures as the only manifestation of the condition.
Most partial epilepsies are caused by a localized brain abnormality, which may or may not be visible on imaging studies. If the cause is found, the epilepsy is said to be symptomatic. If imaging studies are normal, the cause remains elusive and the disorder is said to be cryptogenic. Although imaging studies often have negative results, advances in neuroimaging techniques have resulted in the identification of lesions in increasing numbers of cases. Such lesions include low-grade tumors, hippocampal sclerosis, and subtle cortical dysplasias.
Because of dramatic differences in electroclinical semiology and management, localization-related epilepsies usually are divided into mesiotemporal and neocortical. The most common localization-related epilepsy in adults is mesiotemporal lobe epilepsy, but, in neonates and young children, this is less common than neocortical epilepsy.
The most common cause of temporal lobe epilepsy in candidates for epilepsy surgery in adults is hippocampal sclerosis, while in children, etiologies are dominated by cortical dysplasias and low-grade neoplasms.
Most adult-onset localization-related epilepsies do not have an identifiable etiology (ie, MRI is most often normal); this is well known. When a cause is found, it can include various structural lesions (eg, traumatic scars, neoplasms, vascular malformations, strokes, neuronal heterotopias).
The prevalence of epilepsy is approximately 1% of the population, both in the United States and internationally. Most adult-onset epilepsies are partial epilepsies. Males and females are equally affected. The age-related incidence follows a U-shaped curve, with a peak in the first year of life and an increase during the sixth and seventh decades. (See the image below.)
 View Image | This graph illustrates the 2 peaks of incidence of epilepsy: early and late in life. |
In the United States, the mortality rate from epilepsy decreased from 0.8 deaths per 100,000 population in 1979 to 0.7 deaths per 100,000 population in 1986; it was 0.6 deaths per 100,000 persons for white males and females but 1.7 deaths per 100,000 persons for black males and 1 death per 100,000 persons for black females. No specific data are available for partial epilepsy.
For patient education information, see the Brain and Nervous System Center, as well as Epilepsy.
Obtaining a description of the seizures from the patient and any witnesses is critical. The description needs to include a description of the patient’s state of consciousness during the seizure. Consciousness usually is assessed by the ability of the patient to respond to external stimuli (ie, responsiveness).
Partial seizures are divided into simple, complex, and those that evolve into secondary generalized seizures. Simple and complex seizures are distinguished solely on the basis of the state of consciousness. This is intact in simple partial seizures and impaired in complex partial seizures.
Simple partial seizures are subdivided into 4 categories, according to whether the symptoms are motor, sensory, autonomic, or psychic.
Motor symptoms can vary. They may include motor signs with or without march, versive movements, posturing, and phonatory symptoms.
Sensory symptoms include all 5 senses and a vertiginous sensation. With the exception of vertigo, these usually are characterized by elementary hallucinations.
Autonomic symptoms include the common rising epigastric sensation (typically observed in mesial temporal lobe epilepsy). Less frequent symptoms are vasomotor phenomena and mydriasis.
Psychic symptoms are characterized by various experiences involving memory (déjà-vu, jamais-vu), affect (fear, pleasure), or other complex psychic phenomena such as illusions.
Complex partial seizures include some complex symptomatology (ie, automatisms) and, by definition, an impairment of consciousness. Automatisms consist of involuntary but coordinated motor activity, which tends to be purposeless and repetitive. Common automatisms include lip smacking, chewing, fidgeting, and walking.
Complex partial seizures can begin as simple partial seizures and seizures with impaired consciousness at onset. Complex partial seizures are not subdivided according to coexisting symptoms, no matter how prominent.
The third type of partial seizure evolves into a generalized seizure. This is divided further according to what precedes generalization (simple partial seizure only, complex partial seizure only, simple partial seizure evolving into complex partial seizure). For clinical purposes, however, the partial phase of the seizure often is missed and many patients simply present with a convulsion (secondarily generalized tonic-clonic seizures).
Three genetic partial epilepsies are recognized, as follows:
Age of onset is 15 months to 17 years. One third of patients have a family history of epilepsy, especially rolandic epilepsy.
Symptoms of attacks include the following:
These attacks can occur while the child is awake or sleeping. They tend to occur during the transition period between wakefulness and sleep.
Age of onset is 2-12 years, with a strong peak at 8-9 years.
Characteristic ictal symptoms include the following:
Though these focal seizures are the most characteristic seizure types, they can be quite subtle and are missed easily. The most common mode of presentation is a nocturnal (secondary) generalized tonic-clonic seizure during sleep.
Neurologic examination is normal. The natural history is benign. This syndrome has an excellent prognosis regardless of treatment, with spontaneous remission by age 14-16 years. If treatment is required, options may include carbamazepine, gabapentin, or valproate. Antiepileptic drugs (AEDs) should always be weaned by age 14-16 years.
Autosomal dominant nocturnal (ADNFLE) is a recently described syndrome. Onset is early in life.
ADNFLE is caused by mutation in the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) gene. Several mutations of this gene have been identified as causes of ADNFLE. Despite its established genetic basis, the genetic findings are variable (locus heterogeneity); thus, definite diagnosis is difficult and largely one of exclusion.
Seizures are nocturnal and occur in clusters, mimicking parasomnias. They mostly are brief tonic seizures and rare tonic-clonic convulsions, often preceded by a nonspecific aura.
Seizures often subside with age and may even disappear at adulthood. They usually are controlled with carbamazepine.
In most focal epilepsies, physical examination is unrevealing. A neurologic examination should be done to elicit any cortical abnormality or dysfunction, which would depend on etiology and lesion site.
Laboratory studies, neuroimaging studies, and electroencephalography (EEG) are used in the assessment of partial epilepsies.
Because the type of seizure (partial vs generalized) often is not clear early on, investigate various possible causes for the seizures, including structural abnormalities and toxic and metabolic disturbances. Perform the following test, preferably at seizure onset:
A CT scan of brain without contrast is readily and rapidly available and appropriate in an emergency setting.
MRI of the brain, with and without contrast, delineates structural detail and pathology. Obtain a special temporal lobe cut for mesial temporal sclerosis.
EEG is extremely useful to confirm the diagnosis of epilepsy and to confirm a partial onset. The sensitivity of routine EEG is low but increases somewhat with repeated recordings. When seizures are frequent (>1/wk), EEG video monitoring allows a definitive diagnosis of epilepsy, including its type.
EEG shows sharp waves with a maximum occipital negativity. These often occur in long bursts of spike-wave complexes, and are markedly activated by eye closure.
EEG findings are centrotemporal sharp waves with a characteristic morphology. They occur in repetitive bursts and are often bilateral. These sharp waves are activated markedly by nonrapid eye movement (non-REM) sleep. (For comparison, see the article Normal Sleep EEG.)
Interictal EEG may show epileptiform discharges with a frontal predominance, often observed only in sleep.
Partial epilepsies are generally treated with antiepileptic drugs (AEDs). Nonpharmacologic treatments in certain refractory cases include surgery and dietary modification.
Many AEDs are available. In general, these drugs have similar rates of efficacy. Important factors in choosing among various drugs include potential adverse effects, dosing schedules, drug interactions, available formulations, and cost.
Conventionally, phenytoin, carbamazepine, valproic acid, primidone, and phenobarbital have been used for generalized seizure or epilepsies. The US Food and Drug Administration (FDA) has approved the following AEDs during the past 2 decades: gabapentin, lamotrigine, tiagabine, topiramate, zonisamide, levetiracetam, brivaracetam, oxcarbazepine, eslicarbazepine, cenobamate, and vigabatrin.
Most of these newer AEDs are approved as adjuncts for partial epilepsy. Note that most epilepsy specialists believe that all AEDs that have been approved by the FDA for adjunctive therapy may be effective as monotherapy, and their prescribing practices reflect this.
After they are on the market, many AEDs (eg, carbamazepine, valproic acid, levetiracetam, lamotrigine) are made available in a long-acting or extended-release preparation that may allow once-a-day dosing. It is not clear whether these preparations have sufficient advantages to offset their cost.[4, 5, 6]
Go to Antiepileptic Drugs for complete information on this topic.
Patients with medically refractory seizures may be candidates for nonpharmacologic treatments, which include epilepsy surgery and vagus nerve stimulation.[7] Resective surgery is an underutilized therapeutic option. In the United States, an estimated 20,000-70,000 people each year are candidates for a potentially curative surgical procedure. However, only 5,000 surgeries are performed per year in the 150 epilepsy centers in the United States.
Go Vagus Nerve Stimulation and Epilepsy Surgery for complete information on these topics.
Consider the ketogenic diet as alternative therapy for children with difficult-to-control seizures. It is effective but very strict; compliance is extremely cumbersome.
In the United States, each state has its own laws and regulations about driving with epilepsy. Strict enforcement is nonexistent and depends on reporting by patients. In a few states, reporting the condition is mandatory for physicians. A loophole exists for interstate drivers, in that state governments have no regulations and regulations are poorly enforced federally. Required seizure-free periods for US drivers range from 3 months (many states) to 2 years (Vermont).
If seizures are refractory to the first 2-3 trials of medication, refer patients to a comprehensive epilepsy center to evaluate other treatment options. Nonpharmacologic treatments include surgery, vagus nerve stimulation, and (rarely in adults) the ketogenic diet.
Antiepileptic drugs (AEDs) are the first-line treatment for partial epilepsy. All AEDs are effective, but all have potential adverse effects.
Classic (old) agents include phenobarbital, primidone, phenytoin, carbamazepine, and valproate. After a 15-year hiatus in drug approvals, many new AEDs became available, starting in the early 1990s. Newer drugs approved in the United States include felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), topiramate (Topamax), tiagabine (Gabitril), levetiracetam (Keppra), brivaracetam (Briviact), zonisamide (Zonegran), oxcarbazepine (Trileptal), pregabalin (Lyrica), lacosamide (Vimpat), vigabatrin (Sabril), eslicarbazepine (Aptiom), and cenobamate (Xcopri).
In one phase 3 study, adjunctive perampanel was shown to effectively reduce seizure frequency in patients ≥12 years with partial-onset seizures and was well tolerated.[8]
In November 2013, the FDA approved eslicarbazepine (Aptiom) for adjunctive treatment in patients with partial-onset epilepsy. Approval was based on 3 large multinational, phase 3 trials conducted in >1400 patients with partial-onset seizures inadequately controlled by 1-3 concomitant AEDs (including carbamazepine, lamotrigine, valproic acid, and levetiracetam). Results showed treatment with eslicarbazepine demonstrated statistically significant reductions in standardized seizure frequency compared with placebo (41% vs 22%). Additionally, significantly more eslicarbazepine-treated patients experienced seizure frequency reduction of >50% from baseline.[9, 10]
Clinical Context: Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity. Dose should be individualized. Administer larger dose before retiring if dose cannot be divided equally.
Clinical Context: Carbamazepine may block posttetanic potentiation by reducing summation of temporal stimulation.
Clinical Context: Valproic acid is chemically unrelated to other drugs that treat seizure disorders. Although its mechanism of action not established, its activity may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. It also may potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect.
For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 weeks. This reduction may start at initiation of therapy or be delayed by 1-2 weeks if concern that seizures may occur with reduction. Monitor patients closely during this period for increased seizure frequency.
As adjunctive therapy, divalproex sodium may be added to patient's regimen at 10-15 mg/kg/d. The dose may be increased by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses of less than 60 mg/kg/d.
Clinical Context: Gabapentin is structurally related to GABA, but does not interact with GABA receptors; it is not converted metabolically into GABA or a GABA agonist, and is not an inhibitor of GABA uptake or degradation. Nor does it exhibit affinity for other common receptor sites.
Titration to effect can take place over several days (300 mg on day 1, 300 mg bid on day 2, 300 mg tid on day 3).
Clinical Context: Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity that may have a state-dependent sodium channel-blocking action. This agent potentiates the inhibitory activity of GABA and may block glutamate activity. Monitoring of plasma concentrations is not necessary to optimize therapy. On occasions, the addition of topiramate to phenytoin may require adjustment of the dose of phenytoin to achieve optimal clinical outcome.
Clinical Context: A triazine derivative used in neuralgia, lamotrigine inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.
Clinical Context: An oral AED with weak inhibitory effects on GABA-receptor binding and benzodiazepine-receptor binding, felbamate has little activity at the MK-801 receptor-binding site of the N-Methyl-D-aspartate (NMDA) receptor-ionophore complex. However, felbamate is an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex. Felbamate is not indicated as first-line antiepileptic treatment.
Clinical Context: Oxcarbazepine has pharmacologic activity primarily through its 10-monohydroxy metabolite (MHD). This agent may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Its anticonvulsant effect may also occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics are similar in older children (>8 y) and adults. Young children (< 8 y) have 30-40% greater clearance than older children and adults. Children younger than 2 years have not been studied in controlled clinical trials.
Clinical Context: Eslicarbazepine acetate is a prodrug that is activated to eslicarbazepine (S-licarbazepine), the major active metabolite of oxcarbazepine. It stabilizes neuronal membranes by blocking sodium channels. This action may inhibit repetitive firing and may decrease the propagation of synaptic impulses. It may also increase potassium conductance and modulate the activity of high-voltage activated calcium channels. It is indicated as adjunctive treatment or monotherapy for partial-onset seizures in adults.
Clinical Context: This agent decreases neuron excitability and increases seizure threshold.
Clinical Context: Tiagabine's mechanism of action against seizures is unknown, but is believed to be related to the ability to enhance activity of GABA, which is a major inhibitory neurotransmitter in the CNS.
Tiagabine may block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on surfaces of postsynaptic cells; it also may prevent propagation of neural impulses that contribute to seizures by GABAergic action.
When adding tiagabine to the antiepileptic regimen, modification of concomitant AEDs is not necessary unless clinically indicated.
Clinical Context: Zonisamide is indicated for adjunct treatment of partial seizures with or without secondary generalization. Evidence suggests that it is also effective in myoclonic and other generalized seizure types.
Clinical Context: Levetiracetam is used as add-on therapy for partial seizures. Its mechanism of action is unknown. It has a favorable adverse effect profile, with no life-threatening toxicity reported.
Clinical Context: Precise mechanism of action is unknown. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect. It is indicated as adjunctive therapy for partial-onset seizures in adults and children aged 16 y or older.
Clinical Context: Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. It binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, it reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Pregabalin is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Clinical Context: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. It is indicated as monotheray or adjunctive therapy for partial-onset seizures in children and adults ≥4 years.
Clinical Context: The precise mechanism of action of vigabatrin is unknown. It is an irreversible inhibitor of GABA transaminase (GABA-T). GABA-T metabolizes GABA, an inhibitory neurotransmitter, thereby increasing CNS GABA levels. The use of vigabatrin must be weighed against the risk of permanent vision loss with this agent, which is available only from restricted access program.
Vigabatrin is indicated for adjunctive treatment for complex partial seizures in adults who have had inadequate response to first-line therapy.
Clinical Context: Ethotoin may act in the motor cortex, where it may inhibit the spread of seizure activity. The activity of brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.
Clinical Context: The precise mechanism is unknown, but it has shown to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of GABA-A ion channel. It is indicated for adults with partial-onset seizures as either monotherapy or adjunctive therapy.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
This graph illustrates the 2 peaks of incidence of epilepsy: early and late in life.
This graph illustrates the 2 peaks of incidence of epilepsy: early and late in life.
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