General questions

Question 1

Medications (5) & conditions (2) associated with interictal spikes on EEG.

Answer 1

Meds:

Cefepime; lithium; tramadol; bupropion; clozapine

Conditions:

Thyrotoxicosis & Uremia

Question 2

Major mecahnism difference: BZD vs Phenobarb

Answer 2

BZD: increases the frequency of opening of Cl channels (via Gaba receptors)

Barbiturates: prolong the opening time of Cl channels (also can work extrasynaptically)

Question 3

Antiepileptic drugs that are inducers of the hepatic cytochrome P450 enzyme system.

AED that is both an inducer and is strongly associated with decreased bone mineral density.

Answer 3

Phenytoin; phenobarbital; primidone; carbamazepine, VPA

Note- Valproic acid is an inhibitor of the cytochrome P450 system but is also associated with altered bone metabolism and decreased bone mass.

Question 4

AEDs commonly recognized for their mood-stabilizing properties

Answer 4

carbamazepine; lamotrigine; and valproic acid

Question 5

Antidepressants best avoided in epilepsy

Answer 5

Bupoprion = most infamous

Also (less common): amoxapine; clomipramine; maprotiline.

Question 6

For depression: first-line pharmacologic therapy (minimal interaction with AEDs)

Answer 6

SSRIs with minimal effects on CYP450 isoenzyme: citalopram; escitalopram; and sertraline

Question 7

Medication that can cause PLEDS

Answer 7

Teophylline

Question 8

AED combination that may result in diplopia and dizziness

Answer 8

Phosphenytoin (phenytoin) and CBZ

Question 9

Drugs that aggravate myoclonic or absence seizures

Answer 9

CBZ; gabapentin; Oxcarb; Pregabalin; Tiagabine. (Lamotrigine can aggravate myoclonic jerks)

Question 10

AEDs that may be avoided in Dravet syndrome as they may worsen seizures

Answer 10

Phenytoin, Lamotrigine and CBZ

Question 11

AEDs with most cognitive side effects (4)

Answer 11

Phenobarb; TPM; Zonisamide, and BZDs

Question 12

AEDs with least cognitive side effects (4)

Answer 12

LTG; LVT; Gabapentin; tiagabine

Question 13

Diagnosis of SUDEP if

Answer 13

(1) person had epilepsy;
(2) death occurred suddenly;
(3) death occurred unexpectedly while the person was in a reasonable state of health;
(4) death occurred during normal activity; often while sleeping;
(5) there was no determinable cause of death after autopsy; and
(6) death was not due to SE nor accidental injury; such as falls or asphyxiation from aspiration.

Question 14

Highest risk of SUDEP

Answer 14

Uncontrolled generalized convulsive seizures (not medication non-adherence):

1) Poorly controlled epilepsy (>12 seizures in past yr)
2) Genteralized tonic clonic seizures (>2 GTCs/year)
3) Medication non-adherence
4) Multiple AEDs (>2 AEDs)

Also:

• Mutliple recent AED changes
• IQ < 70
• ? Nocturnal Seizures

Question 15

Syncopes (2 primary types)

Answer 15

The two main causes of syncope are changes in vasovagal tone and cardiac arrhythmia (cardiogenic)

Most cases of vaso-vagal syncope (91%) are associated with some type of physiologic sign or symptom; including sweating; nausea; vomiting; visual dimming; motor weakness; and palpitations. These signs and symptoms may occur in isolation or in combination.

By comparison, syncopal events resulting from cardiac arrhythmia are not accompanied by prodromal symptoms in 50% of cases. When symptoms are present; diffuse weakness and dizziness are the most common symptoms.

Vasovagal syncope is more common in younger patients (mean age of 40); while syncope resulting from cardiac arrhythmia is more common in older patients (mean age of 68).

Question 16

Ketogenic diet contraindications

Answer 16

Contraindicated in patients with:

• Pancreatitis
• Liver disease (hepatic failure, porphyria)
• Carnitine deficiency
• Metabolic conditions: pyruvate carboxylase deficiency and beta-oxidation defects

Question 17

Ketogenic diet -first line treatment for:

Answer 17

GLUT1 deficiency & pyruvate dehydrogenase deficiency.

Question 18

Contraindications with use of propofol & Ketogenic diet concurrently:

Answer 18

May lead to propofol infusion syndrome.

Question 19

Ketogenic diet: chances of responding:

Answer 19

The chance that a child will respond with a greater than 50% seizure reduction is about 50%.

Question 20

Ketogenic diet: types of fat

Answer 20

Fats are usually long chain fatty acids or medium chain tryglicerides (which are better absorbed and produce more ketones).

Question 21

Efficacy of ketogenic diet vs MAD

Answer 21

The effectiveness of the the MAD is comparable to the KD in children and adults.

Question 22

Is the efficacy of ketogenic diet efficacy correlated with ketosis?

Answer 22

Seizure reduction is not correlated with the degree of acidosis or ketosis.

Question 23

NES predictors of poor outcome

Answer 23

Predictors of poor outcome:

• older age
• prominent motor features
• lower education achievement.

Question 24

Patient group/demographic most likely to have NES misdiagnosed?

Answer 24

Veterans are most likely to have their nonepileptic events mischaracterized as epileptic seizures.

Question 25

Best initial choice for young female with JME

Answer 25

LVT/Keppra

Question 26

Predictors of poor surgical neuropsychological outcome

Answer 26

• Higher pre-surgical cognitive performance
• Older age
• Absence of hippocampal atrophy on MRI
• Surgery on the dominant side.

Question 27

VNS and bradycardia: Which agus nerve is more highly associated (R vs L)?

Answer 27

Fibers from the right vagus nerve innervate the sinoatrial node; while fibers from the left nerve innervate the atrioventricular. Stimulation of the right side is postulated to cause bradycardia; but with higher settings bradycardia can be seem with stimulation of either nerve.

Question 28

DBS - best responders?

Answer 28

Temporal lobe epilepsy

Question 29

DBS side effects

Answer 29

Memory problems; depression; hemorrhage and infection (in this order)

Question 30

OTC supplement that may lower AEDs concentrations

Answer 30

St Johns Wort

Question 31

Medications or OTC products that increase AEDs concentrations

Answer 31

Macrolide antibiotics; calcium channel blockers (diltiazem; verapamil); antifungals (fluconazole; ketoconazole); antivirals (indinavir; ritonavir); antidepressants (fluvoxamine; nefazodone); and grapefruit juice.

Question 32

AEDS that lower OCP efficacy?

Answer 32

• Phenobarbital
• Phenytoin
• CBZ / Oxcarbazepine / Eslicarbazepine
• Felbamate
• Topiramate

Note: Lamotrigine is not metabolized by the hepatic enzymes, but OCPs may significantly reduce the level of lamotrigine. The dose of lamotrigine may need to be adjusted if OCPs are started or stopped during the course of AED treatment.

Question 33

AEDs with highest risk of congenital malformations?

Answer 33

• Valproate (highest risk) > PHB > TPM (cleft defects)
• Carbamazepine has a slight risk of spina bifida; but its overall risk for malformations is low.
• Lamotrigine (implicated in cleft defects, not well-substantiated); levetiracetam; and oxcarbazepine have low overall risk of major congenital malformations.
• Data are inadequate to determine the risks for many antiepileptic drugs (e.g.; gabapentin; lacosamide; and zonisamide).

Question 34

Drug whose levels fluctuates the most during pregnancy

Answer 34

Lamotrigine

Question 35

GLUT1 defficiency (De Vivo disease)

• Gene?
• Protein?
• Inheritance?
• First sign in infancy?
• % with seizures?
• Diagnosis? (level of CSF lactate?)
• Tx

Answer 35

GLUT1 deficiency syndrome is caused by mutations in the SLC2A1 gene

• protein: glucose transporter protein type 1 (GLUT1).
• Autosomal dominant - usually de novo.
• first sign may be irregular eye movements.
• up to 90% of patients have seizures,
• In newborns, Microcephaly, spasticity, complex movement disorders and developmental delay are common.
• Diagnosis: genetic testin (also: Low CSF lactate and glucose concentrations)
• Tx: Ketogenic diet

Question 36

Nonketotic Hyperglycinemia (Glycine encephalopathy)

• Genes?
• Inheritance?
• Presentation?
• EEG findings?

Answer 36

Mutations in the AMT and GLDC genes (which code for glycine cleavage enzyme complex) cause glycine encephalopathy.

• Autosomal recessive pattern,
• Appears shortly after birth with lethargy, feeding difficulties, hypotonia, abnormal jerking movements, and life-threatening problems with breathing. Profound intellectual disability and seizures that are difficult to treat follow.
• EEG: “suppression-burst” pattern in the neonatal period, changing to hypsarrhythmia during early or mid-infancy

Question 37

Occipital epilepsies (3)

Answer 37

Panyiotopolous syndrome (self-limited occipicatl focal epilepsy syndrome)

Celiac Dz: he association between occipital seizures and celiac disease, with or without bilateral occipital calcifications, has been well-documented.

Lafora body disease: frequently associated with occipital seizures. The diagnosis should be suspected when myoclonus and progressive mental decline are present.

Question 38

Tuberous sclerosis

• Genes (2)
• Proteins (2)
• Cognitive/behavioral Features:
• Brain tumor Types (3):
• Skine FIndings (3):

Answer 38

- Caused by a mutation of either of 2 genes: TSC1 and TSC2, which code for 2 proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors.

- Cognitive/behavioral features: 50% have learning difficulties; 25% and 61% of affected individuals meet the diagnostic criteria for autism.

- Three types of brain tumors may be associated with TSC:

1) Giant cell astrocytoma: (grows and blocks the CSF flow leading to dilatation of ventricles causing headache and vomiting)
2) Cortical tubers (are thought to represent foci of abnormal neuronal migration)
3) Sub-ependymal nodules: form in the walls of ventricles.

- Some form of dermatological sign will be present in 96% of individuals with TSC: 1) Facial angiofibromas (“adenoma sebaceum”)

2) Periungual fibromas
3) Hypomelanic macules (“ash leaf spots”) - noted by UV light (Wood’s lamp)
4) Forehead plaques
5) Shagreen patches