Top 10 Seizure Treatment Tips with Cases

00:01 So let's talk about some common tips.

00:03 So the top 10 seizure treatment tips when we're selecting and using medications.

00:10 So let's talk about some seizure tips or clinical pearls to think about when selecting a seizure treatment.

00:17 And we'll go through some cases.

00:19 The first is a 13-year-old boy, who's referred from his PCP.

00:23 The 13-year-old boy presents to the ED on referral from his PCP.

00:27 He initially presented with problems in school, staring about eight months ago.

00:31 Initially was diagnosed with ADD but recently there's been some concern for seizures.

00:37 He's also has depressed mood and at times is reported to have episodes of pressured speech and grandiose behavior.

00:43 He was placed on Tegretol three weeks ago, as he was not able to get and see a neurologist for another two months.

00:49 Unfortunately, he has developed seizures that have worsened and have now had five spells a day, where he was only having up to 1 to 2 weeks before.

00:59 So what's going on in this case? Well, this is someone, who initially had episodes of behavioral arrest that were thought to be from ADD, but were likely underlying seizures.

01:10 He was placed on carbamazepine, and then those episodes worsened in frequency.

01:15 This is a key clinical pearl about what medications worsen primary generalized seizures.

01:20 The clinical description is consistent with a generalized onset epilepsy.

01:25 And here we see one of the common offenders.

01:28 These medications include carbamazepine, as in this case.

01:31 Vigabatrin, gabapentin, Trileptal or oxcarbazepine, and Tiagabine.

01:37 These are medications that we don't tend to use for primary generalized epilepsy.

01:42 We can in selected cases, but we don't tend to because they can worsen those patients seizures.

01:46 A good clinical pearl.

01:50 Let's consider a 34-year-old woman with a long history of temporal lobe epilepsy who presents to the ED in status epilepticus.

01:57 She developed progressively worsening complex partial seizures over the past six months.

02:02 She's been on phenytoin and for many years.

02:04 Given an increase in seizure frequency, her phenytoin has gradually been increased and increased to a serum level around 25.

02:11 With continued seizures, valproic acid is added three days prior to her presentation.

02:17 You recommend that the ED checker levels to determine compliance.

02:20 Her total phenytoin level is high.

02:23 Her valproic acid level is normal.

02:26 So what antiepileptic medications have strong protein-protein interaction? And that's what's going on with this patient.

02:33 Phenytoin and valproic acid have protein-protein binding and both interact.

02:38 When we add the valproic acid to the phenytoin the valproic acid binds to protein more than phenytoin and we see an increase in the free phenytoin level.

02:49 Protein binding is important for medications like phenytoin and valproic acid.

02:53 Valproic acid has a greater affinity to protein than phenytoin.

02:58 And adding valproic acid to phenytoin displaces the phenytoin in from its bound state on the protein, resulting in a lower serum concentration, but higher free drug levels.

03:08 And so patients can become phenytoin toxic.

03:12 Let's consider a 28-year-old woman who presents for management of a known seizure disorder.

03:17 She has been on Topamax for three years and was tolerating it well.

03:21 But his reporting increased issues with difficulty with her thinking.

03:24 She's interested in changing medications and is wondering about carbamazepine or Tegretol.

03:29 Given associated mood complaints that she has.

03:32 You agree starter on 200 milligrams twice a day, and titrate up to 400 milligrams twice a day after one week.

03:40 You see the patient back after three months, and she says, that at first, she felt horrible.

03:44 Had intense vomiting sodium channel side effects after each dose of the medication.

03:49 But over time, this resolved.

03:51 Now, she's concerned that the medication is not working, because she's back to having one to two light seizures per week.

03:57 So what's going on with this patient? Well, this is a great example of what anti-seizure medicines are associated with hepatic auto-induction? And the one to remember is carbamazepine.

04:10 Carbamazepine causes auto-induction.

04:12 It induces the expression of the CYP3A4 enzyme in the liver.

04:17 This enzyme is involved in metabolism of carbamazepine.

04:20 So as the medication is initiated, the liver at the first doses doesn't have the CYP3A4 enzyme around.

04:27 So it's not rapidly metabolized.

04:30 Over time as the liver becomes used to the carbamazepine, there's increased expression of the CYP3A4 enzyme.

04:37 Increased metabolism of the carbamazepine and lower drug levels.

04:42 So carbamazepine is typically a drug that we start over the first couple of weeks and check a level after several weeks, and would plan to further titrate the medication based on the degree of hepatic auto-induction.

04:53 And this is a great clinical example of what's going on for this patient.

04:58 And then, let's consider an 18-year-old woman who presents to your clinic six months after a new patient appointment for a treatment evaluation of seizures.

05:06 She's very furious.

05:08 She says that she is not married and has become pregnant since you saw her last.

05:13 She has been on birth control pills, consistently over this period of time and is not sure how this happened.

05:19 And she blames you.

05:21 This is a good example of counseling needed for patients when we're starting selected seizure medications.

05:26 We must warn our patients about the potential of oral contraceptive failure on selected agents.

05:32 So what are those anti-seizure medications that can interfere with activity of oral contraceptive pills? Well, here's a list.

05:40 Levetiracetam, gabapentin, tiagabine, vigabatrin, zonisamide, topiramate, all of those medications have no effect on endogenous steroid hormone concentrations.

05:50 They're okay to use without seeing problems with oral contraceptive pills.

05:55 The medications that can cause contraceptive failure are lamotrigine, phenytoin, phenobarbital, and carbamazepine.

06:03 And important to counsel patients when starting these medications.

06:08 And then let's consider a 13-year-old boy with mild mental retardation who presents for a return appointment for management of medically refractory generalized epilepsy.

06:17 He was on Lamictal monotherapy and things were stable on this medication for many years, until recently.

06:23 His mother called with increased seizure frequency and breakthrough seizures about one month ago.

06:29 He's six inches taller and skinnier at this visit then last.

06:32 His mother was concerned about increased seizure frequency and asked and to start him on an additional medication.

06:38 You recommend valproic acid.

06:40 She says, that since that, since starting valproic acid over the past week, he's been sleepy or and sleeper, and seemed somewhat confused.

06:49 So what anti-seizure medication is associated with hyperammonemia? That's what's going on in this case.

06:55 Hyperammonemia is associated with valproic acid.

06:58 This is a medication that can be associated with idiosyncratic pancreatitis and hepatitis as well as, as spontaneous increases in circulating ammonia levels.

07:09 Hyperammonemia can occur in the absence of transaminitis or other LFT abnormalities.

07:14 And we note that this can be particularly the case when valproic acid is combined with lamotrigine where there is drug-drug interaction.

07:21 So this is a good example of a patient who's suffering from hyperammonemic-induced encephalopathy that was precipitated by the combination of valproic acid and lamotrigine.