neurologic disorders
Seizure Disorders
Treatment of Seizure Disorders
Elimination of the cause if possible Avoidance of or precautions during situations when loss of consciousness could be life threatening Medications to control seizures urgery if≥2 medications in therapeutic doses do not control seizures For information about specific antiseizure medications, see Antiseizure Medications . Optimal treatment of seizures is to eliminate the causes whenever possible. If the cause cannot be corrected or identified, antiseizure medications are often required, particularly after a second seizure; usefulness of antiseizure medications after a single seizure is controversial, and risks and benefits should be discussed with the patient. Because the risk of a subsequent seizure is low, medications may be withheld until a second seizure occurs, particularly in children. In children, certain antiseizure medications cause important behavior and learning problems. During ageneralized tonic-clonic seizure,injury should be prevented by loosening clothing around the neck and placing a pillow under the head. Attempting to protect the tongue is futile and likely to damage the patient’s teeth or the rescuer’s fingers. Patients should be rolled onto their side to prevent aspiration. These measures should be taught to the patient’s family members and coworkers. Because focal-onset seizures can become generalized, patients are at risk of losing consciousness and thus should be advised to take certain precautions. Until seizures are controlled, patients should refrain from activities in which loss of consciousness could be life threatening (eg, driving, swimming, climbing, operating power tools, bathing in a bathtub). After seizures are completely controlled (typically for>6 months), many such activities can be resumed if appropriate safeguards (eg, lifeguards) are used, and patients should be encouraged to lead a normal life, including exercise and social activities. In a few states, physicians must report patients with seizures to the Department of Motor Vehicles. However, most states allow automobile driving after patients have been seizure-free for 6 months to 1 year. Patients should be advised to avoidcocaineand some other illicit drugs (eg, phencyclidine, amphetamines), which can trigger seizures, and to avoid alcohol. Some medications (eg,haloperidol, phenothiazines) may lower seizure threshold and should be avoided if possible. Family members must be taught a commonsense approach toward the patient. Overprotection should be replaced with sympathetic support that lessens negative feelings (eg, of inferiority or self-consciousness); invalidism should be prevented. Institutional care is rarely advisable and should be reserved for severely cognitively impaired patients and for patients with seizures so frequent and violent, despite treatment with antiseizure medications, that they cannot be cared for elsewhere. Dravet syndrome is treated with valproate,clobazam, ortopiramate, but seizures are often refractory to these medications.Carbamazepine,phenytoin, andlamotriginecan worsen myoclonus and exacerbate seizures.Cannabidioloral solution may also be used as adjunctive treatment of seizures in Dravet syndrome. Most generalized-onset and focal-to-bilateral tonic-clonic seizures remit spontaneously in several minutes or less and do not require emergency treatment with medications. However, status epilepticus and most seizures lasting>5 minutes require medications to terminate the seizures, with monitoring of respiratory status. Endotracheal intubation is necessary if there is any indication of airway compromise. The sooner antiseizure medications are started, the better and the more easily seizures are controlled. IV access should be quickly obtained, and patients are givenlorazepam0.05 to 0.1 mg/kg IV (typically a 4-mg IV dose for adults) at a rate of 2 mg/minute. Larger doses are sometimes required. Afterlorazepamis given, a second, longer-acting antiseizure medication is indicated. There is no consensus or evidence-based guideline indicating which longer-acting medication is preferred ( Treatment references ). Many experts choose one of the following: Fosphenytoin15 to 20 mg/kg PE (phenytoinequivalents) mg/kg IV, given at a rate of 100 to 150 PE/min Phenytoin15 to 20 mg/kg IV, given at a rate of 50 mg/minute 1500 to 3000 mg IV over 25 minutes, then 1500 mg orally 2 times a day ( Treatment references ) Valproate 20 to 40 mg/kg IV (loading dose) over 30 minutes followed by 4 to 8 mg/kg orally 3 times a day (total daily IV dose should be equivalent to the total daily oral dose (expressed asvalproic acid) and divided every 6 hours) The dose offosphenytoinis given inphenytoinequivalents (PE);fosphenytoin1.5 mg is equivalent tophenytoin1 mg. If seizures persist after these doses are used, an additional 5 to 10 PE mg/kg offosphenytoinor 5 to 10 mg/kg ofphenytoincan be given. If IV access cannot be obtained, options include IMfosphenytoinand sublingual or rectal benzodiazepines. Seizures that persist after use oflorazepamandphenytoin(or another second antiseizure medication) define refractory status epilepticus. Recommendations for a third antiseizure medications vary and includephenobarbital,propofol,midazolam,levetiracetam, and valproate. Dose ofphenobarbitalis 15 to 20 mg/kg IV at 100 mg/minute (3 mg/kg/minute in children); continued seizures require another 5- to 10-mg/kg dose. A loading dose of valproate 20 to 40 mg/kg IV is an alternative. At this point, if status epilepticus has not abated, intubation and general anesthesia are necessary. The optimal anesthetic to use is controversial, but many physicians usepropofol1 to 2 mg/kg at 100 mg/minute orpentobarbital5 to 8 mg/kg (loading dose) followed by infusion of 2 to 4 mg/kg/hour until EEG manifestations of seizure activity have been suppressed. Infusions should be continued for ≥ 24 hours, then stopped, so that an EEG can be repeated and reassessed. Inhalational anesthetics are rarely used. After initial treatment, the cause of status epilepticus must be identified and treated. Medications are given to prevent seizures if head injury causes significant structural injury (eg, large contusions or hematomas, brain laceration, depressed skull fracture) or if a Glasgow Coma Scale (GCS) score is<10. These medications reduce risk of seizures during the first week after injury but do not prevent permanent posttraumatic epilepsy months or years later. They should be stopped after 1 week unless seizures occur. If seizures begin>1 week after head injury, long-term treatment with medications is required. Antiseizure medications may be required indefinitely in patients with juvenile myoclonic epilepsy and in patients who require multiple antiseizure medications for seizure control. However, many types of seizures (eg, most febrile seizures, seizures due to alcohol withdrawal, seizures that do not recur) do not require treatment with antiseizure medications. ). For more detailed treatment information, see Choice of Medication for Long-Term Treatment . As many as 40% of patients have new-onset seizures that will become refractory to medical treatment; these patients may be candidates for conventional epilepsy surgery ( Treatment references ). If seizures originate from a focal, resectable area in the brain, resection of the epileptic focus usually improves seizure control markedly. If the focus is in the anteromesial temporal lobe, resection eliminates seizures in approximately 60% of patients ( Because surgery requires extensive testing and monitoring, these patients are best treated in specialized epilepsy centers. 50% in about 40% of patients ( Treatment references ). After the device is programmed, patients can activate it with a magnet to abort an imminent seizure. Adverse effects of vagus nerve stimulation include deepening of the voice during stimulation, cough, and hoarseness. Complications are minimal. Duration of effectiveness is unclear. The responsive neurostimulation system is a programmable neurostimulator device that is implanted intracranially and connected to cortical strip leads that are surgically placed in up to 2 seizure foci within the brain ( Treatment references ). When the system detects epileptiform activity, it directly stimulates the seizure focus, with the aim of disrupting epileptiform activity before a seizure can develop. It is an adjunctive surgical therapy to reduce the frequency of seizures in adults with medically intractable focal-onset seizures when they are not candidates for conventional epilepsy surgery. Brain responsive neurostimulation has been effective in treating different types of drug-resistant seizures ( Treatment references , 1.Kapur J, Jordan Elm J, Chamberlain JM, et al: Randomized trial of three anticonvulsant medications for status epilepticus.N Engl J Med. 381 (22):2103–2113, 2019. doi: 10.1056/NEJMoa1905795 2.Chamberlain JM, Kapur J, Shinnar S, et al: Efficacy oflevetiracetam,fosphenytoin, and valproate for established status epilepticus by age group (ESETT): A double-blind, responsive-adaptive, randomised controlled trial.Lancet395 (10231):1217–1224, 2020. doi: 10.1016/S0140-6736(20)30611-5 Epub 2020 Mar 20. 3.Engel J Jr: The current place of epilepsy surgery,Curr Opin Neurol31 (2):192–197, 2018. doi: 10.1097/WCO.0000000000000528 4.Dalio MTRP, Velasco TR, Feitosa IDF, et al: Long-term outcome of temporal lobe epilepsy surgery in 621 patients with hippocampal sclerosis: Clinical and surgical prognostic factors.Front Neurol13:833293, 2022. doi: 10.3389/fneur.2022.833293 eCollection 2022 5.Toffa DH, Touma L, El Meskine T, et al: Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: A critical review.Seizure83:104–123, 2020. doi: 10.1016/j.seizure.2020.09.027. Epub 2020 Oct 10 6.Bergey GK, Morrell MJ, Mizrahi EM et al: Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.Neurology84:810–817, 2015. doi: 10.1212/WNL.0000000000001280 7.Nair, DR, Laxer KD, Weber PB, et al: Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.Neurology95 (9):e1244-e1256, 2020. doi: 10.1212/WNL.0000000000010154 Epub 2020 Jul 20. 8.Geller EB, Skarpaas TL, Gross RE, et al: Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.Epilepsia58 (6):994–1004, 2017. doi: 10.1111/epi.13740 