Secondarily generalized tonic-clonic seizures

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By Robert L Beach MD PhD and Rajdeep Singh MD

Therapeutic options of secondarily generalized tonic-clonic seizures include medical therapy and surgery. Along with therapy, management should include counseling of the patient regarding the condition and providing knowledge of standard seizure precautions.

Medical therapy. Medical therapy with a single anticonvulsant is the initial primary approach to management of secondarily generalized tonic-clonic seizures. The use of a single AED reduces the risks of idiosyncratic and dose-related toxic reactions, the cost of medications, and chances of drug interactions and increases the compliance of therapy. The initial drug selection is based on consideration of syndrome and seizure type, potential side effects, cost, comorbidities and drug interactions. Both older and newer AEDs have efficacy for the treatment of partial seizures. According to the American Academy of Neurology guidelines, gabapentin, lamotrigine, oxcarbazepine, and topiramate are among the newer agents that can be used in initial monotherapy (French et al 2004). The International League Against Epilepsy (ILAE) published evidence-based guidelines in 2006 for the initial monotherapy of newly diagnosed patients. In adults with partial-onset seizures, there was Level A evidence for carbamazepine and phenytoin. Valproic acid was probably efficacious with level B evidence, and there was level C evidence for gabapentin, lamotrigine, oxcarbazepine, phenobarbital, topiramate, and vigabatrin (Glauser 2006). Carbamazepine has generally been considered a first drug of choice in the treatment of secondarily generalized tonic-clonic seizures (Ramsay and DeToledo 1997). A large, unblinded, randomized control trial (SANAD) compared carbamazepine with newer AEDs, including gabapentin, lamotrigine, oxcarbazepine, and topiramate (Marson et al 2007). The trial found lamotrigine to be significantly better for time-to-treatment failure for any reason (inadequate seizure control or unacceptable side effects). Further analysis showed lamotrigine to be better mainly because of its better tolerability than carbamazepine. Carbamazepine was still slightly better than lamotrigine for the secondary efficacy outcome of time to first seizure.

Vagus nerve stimulation (VNS). Vagus nerve stimulation is used as a safe adjunctive therapy to intractable seizures. Complex partial seizures with secondary generalizations respond well to this therapy with significant reduction in seizures as well as improvement in alertness (Buoni et al 2004). Vagus nerve stimulation involves repeated stimulation of the left vagus nerve through implanted electrodes. Despite studies in animals and man, which show changes in brain electrophysiology, metabolism, and neurochemistry, the mode of action remains uncertain. Stimulation is delivered via a programmable generator, allowing variation in current, pulse, frequency, and duty-cycle. Complications of this treatment can be divided into: adverse events related to surgery, late complications, and stimulation-induced effects. Adverse surgical outcomes are acceptably low in experienced hands (Tecoma and Iragui 2006). These include infection, hematoma, reversible left vocal cord paralysis, and incorrect lead placement. Late complications include lead breakage, device extrusion, and device migration. Stimulation-induced effects, such as hoarseness, cough, and dysphagia, are intensity dependent, diminish over time, and are usually not treatment-limiting.

Intracranial stimulation has received renewed attention in the treatment of epilepsy. Cortical stimulation in response to electrographic ictal or preictal activity has shown promising data in animal and preliminary human studies. An investigational implantable responsive neurostimulator system – ‘”NeuroPace RNS,” is being evaluated in a multicenter, randomized, double-blinded trial for the treatment of medically refractory epilepsy (Sun et al 2008). Deep-brain stimulation of the anterior thalamus, evaluated in the SANTE trial, showed improved seizure control in most patients (findings presented by Dr Robert Fisher at the 2008 American Epilepsy Society meeting in Seattle).

Surgical therapy. Surgery should be considered once the patient has failed a second drug trial because once a patient has failed 2 drug trials, chances of achieving seizure control with additional drug trials or combination therapy are less than 20% (Thadani and Taylor 2007). Common disorders that can be successfully addressed with surgery include low-grade tumors, vascular lesions, cortical dysplasias, and mesial temporal or hippocampal sclerosis. The key to successful epilepsy surgery is multimodality localization of the seizure focus. Video-EEG recording with scalp and or with intracranial EEG plays a vital role in localization. New imaging technologies, including PET scans, ictal SPECT, and magnetic resonance spectroscopy, are being increasingly used to help in localization and placement of intracranial electrodes. Seizure control can be anticipated in 50% to 70% of patients who undergo a focal resection (Thadani and Taylor 2007).

In This Article

Historical note and nomenclature
Clinical manifestations
Differential diagnosis
Diagnostic workup
Syndromes and diseases in which the seizure type occurs
Prognosis and complications
References cited