Focal (Partial) Epilepsy Treatment & Management

Updated: Mar 14, 2022
  • Author: Muhammad H Jaffer, MD; Chief Editor: Helmi L Lutsep, MD  more...
  • Print
Treatment

Approach Considerations

Focal epilepsies are generally treated with antiseizure medications (ASMs). Nonpharmacologic treatments in certain refractory cases include surgery and dietary modification.

Next:

Antiseizure Medication Therapy

Approximately two-thirds of epilepsy patients will respond to either anti-seizure medication (ASM) monotherapy or combination therapy. There are approximately 30 ASMs available and, in general, drugs have similar rates of efficacy with limited comparative data. Important factors in choosing among various drugs include potential adverse effects, dosing schedules, drug interactions, available formulations, and cost.

In patients taking their first ASM, adverse effects are seen in up to 30% of patients, while polytherapy can lead to adverse effects in up to 90% of cases. Most common side effects include dizziness, drowsiness, and slowed cognition; these may be dose-dependent. Some ASMs (phenytoin, carbamazepine, lamotrigine) also can predispose to a rash and severe reactions such as Stevens-Johnson syndrome. Others may lead to weight gain (gabapentin, valproate) or weight loss (topiramate, zonisamide). In pregnant patients or women of childbearing age, it is important to consider teratogenic effects of ASMs and lamotrigine and levetiracetam have the lowest risk profile for congenital malformations. [32]

A “start low, go slow” titration approach over weeks to months is recommended when starting a new ASM and has been shown to reduce the risk of adverse effects. Patients may require ASM changes due to a lack of efficacy or intolerability. If the first ASM fails because of lack of tolerability, it should be replaced with an alternative monotherapy. If the first ASM fails because of a lack of efficacy, one can opt for either replacement of monotherapy or adjunctive therapy. Monotherapy conversion is favored when the first ASM was not well-tolerated or was totally ineffective; this is also preferred in elderly patients who are taking several medications, women of childbearing age contemplating pregnancy, patients with compliance issues, and financial issues. Adjunctive therapy would be preferred if the first ASM was well-tolerated and partially effective. There is a benefit to combining different mechanisms of action and use of redundant mechanisms may predispose to tolerability issues. Tapering or discontinuation of the baseline ASM should only be done once an efficacious dose of the replacement therapy is reached, and this may be facilitated through laboratory drug level monitoring. One should also pay attention to the patient’s schedule and in those with a busy lifestyle, a medication with an extended half-life and one-time daily dosing is recommended. [37] In all cases, a shared decision-making process between the patient and the provider is highly encouraged to improve compliance. [38]

For focal epilepsies, narrow-spectrum agents are typically effective, although broad-spectrum agents can improve seizure frequency in focal epilepsies as well with variable efficacy. Several ASMs, especially those that are inducers or inhibitors of the cytochrome P450 system, may lead to undesirable drug interactions. In childbearing age women, enzyme inducers such as carbamazepine and phenytoin can increase the clearance of oral contraceptives and precipitate unwanted pregnancy; oral contraceptives have been shown to also decrease plasma concentrations of lamotrigine. In patients who are on warfarin, enzyme inhibitors such as valproate can impair clearance of anticoagulation. In patients with multiple comorbidities, use of levetiracetam, lamotrigine, lacosamide, and gabapentin is favored due to limited drug interactions. Finally, use of lamotrigine and valproate in combination may have synergistic effects but a sensitive dosing approach is necessary.

Cost is a sensitive consideration for some patients, especially those without insurance; in such cases it is feasible to switch generic formulations that have Food and Drug Administration (FDA)-validated bioequivalence to their brand-name alternatives. [39]

Of note, new FDA guidelines allow for the extrapolation of ASM efficacy data in adults with focal epilepsy to pediatric populations over the age of four, although safety studies are still required. The FDA has also allowed for adjunctive ASM approval to be extrapolated for monotherapy. [40]

Go to Antiepileptic Drugs for complete information on this topic.

Previous
Next:

Surgical Care

Approximately 30%–40% of patients with focal epilepsy become intractable despite the use of anti-seizure medications (ASMs). Drug-resistant epilepsy is defined as the failure of adequate trial of two tolerated, appropriate chosen and used ASM schedules to achieve sustained seizure freedom. Several clinical trials have shown the efficacy of surgical over medical treatment for drug-resistant epilepsy, therefore referral of such patients to a qualified epilepsy center is paramount. Unfortunately, only one percent of patients with drug-resistant epilepsy are appropriately referred, and the reasons for this delay may be patient fear, lack of healthcare provider knowledge, lack of adequate healthcare access, or social and cultural issues. Fortunately, epilepsy surgery is highly safe, effective, and can be tailored to the patient’s needs; another highly attractive consideration is that epilepsy surgery is the only therapeutic option that provides a chance for complete remission of epilepsy. The referenced article provides a useful overview of the safety, efficacy, and mortality/outcome data regarding epilepsy surgery. [41]

Resective surgery remains the gold standard and may include variations such as callosotomy, hemispherectomy, and functional disconnection surgeries. If the epileptic focus is difficult to approach via open surgery or a less invasive option is specifically preferred, a thermal laser ablation may be performed and achieves comparable results to open-resection in well-selected patients. An ultrasound-induced thermal ablation may also be considered.

Although surgical resection is the standard of care in such cases, when eloquent cortex is implicated in the epileptic focus there is a risk for significant post-operative neurologic impairment. Neuromodulation devices can serve as a reasonable adjunctive therapy for intractable focal epilepsy in such cases where resection is too high-risk for neurologic injury. These devices utilize an internal pulse generator (IPG) to deliver electrical impulses that may disrupt hypersynchrony at the site of seizure initiation, produce a conduction block in seizure propagation, and attenuate cortical hyperexcitability and gating networks.  We will review here the three FDA-approved neuromodulation devices with attention to their mechanisms, their advantages/disadvantages, and the clinical evidence to support their use. Further details may be found in the reference article attached. [42]

Vagal nerve stimulation (VNS) is one of the earliest devices to have received FDA approval: a coiled lead is threaded around the vagus nerve and connected to an IPG implanted superficially to the pectoral muscle. VNS is an open-loop system, meaning that it delivers continuous electrical stimulation in a pre-defined pattern. However, several models now include a tachycardia detection algorithm that can deliver extra stimulation under the presumption of ictal tachycardia. VNS is theorized to increase activity in the nucleus tractus solitarius, activating the locus coeruleus and raphe nuclei which release norepinephrine and serotonin respectively; both neurotransmitters have been found to have anti-epileptic effects in the brain. Advantages of VNS include its safer extracranial implantation, its conditional compatibility with MRI, and its easy programmability; disadvantages/risks include vocal cord paralysis, bradycardia, cough, and neck pain. In prospective multicenter studies, the median percentage seizure reduction with VNS was 40%  after three years with nearly 22.5% achieving greater than 90% reduction in seizures.

Responsive neurostimulation (RNS) is a closed-loop device (ie, delivers targeted stimulation only when ictal activity is detected) which delivers electrical impulses to the putative seizure-onset zone. The electrodes rest on the neocortex and serve the dual purposes of recording brain activity (electrocorticography) and delivering abortive stimulation; meanwhile, the battery and circuit board are recessed in a ferrule under the scalp. Functioning analogously to a cardiac pacemaker, RNS detects and disrupts synchronized epileptiform activity in the focus of interest through direct electrical stimulation while also altering the long-term plasticity of epileptogenic networks. Advantages include targeted/intermittent stimulation, the potential for long-term electrocorticography (can track seizure patterns longitudinally), and high efficacy; disadvantages include lack of MRI compatibility, necessity to specifically localize the seizure-onset zone, and approximately 2% risk of infection/intracranial hemorrhage. A multicenter clinical trial with 191 patients enrolled demonstrated median percent seizure reduction of 60%–70% by 6 years post-implantation.

Deep brain stimulation (DBS) is an open-loop device in which 2 depth electrodes with 4 contact points are placed within the brain parenchyma and connected via a wire to an IPG that resides in the subclavicular region. Although many targets are still under active investigation (centromedian nucleus of thalamus, hippocampus, nucleus accumbens), the implantation site most supported by the current data is the anterior nucleus of the thalamus: a pivotal study in 2010 known as SANTE (Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy) demonstrated 69% seizure reduction at 5 years post-implantation. Although the mechanism remains theoretical, the anterior thalamic nucleus plays a role in the Papez circuit that involves several of the limbic structures involved in epilepsy. It is thought that stimulation at the anterior nucleus of the thalamus may desensitize the neural network and thus increases the precipitation threshold for seizures. Advantages to DBS include its relatively high efficacy and its plausibility to also improve outcomes in multifocal epilepsy; however, disadvantages include implant site infections, lead misplacement, and neurobehavioral impairment.

Go Vagus Nerve Stimulation and Epilepsy Surgery for complete information on these topics.

Previous
Next:

Dietary Modification

Consider the ketogenic diet or a modified Atkins diet as an alternative therapy for epileptic seizures. It is effective, even in highly refractory cases, but very strict; compliance may be extremely cumbersome. [43]

Previous
Next:

Activity Restriction

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. [44]

Previous
Next:

Consultations

As previously discussed, if seizures are refractory to the first 2–3 trials of medication, refer patients to a comprehensive epilepsy center to evaluate other treatment options. This is important not only for surgical considerations in drug-resistant epilepsy but also to identify “pseudoresistance,” which may be secondary to medication non-compliance, misdiagnosed non-epileptic events, or failure to identify a treatable cause.

Previous