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PharmSoc Year 2 Epilepsy Tutorial Questions – Rebecca Irvine SBA 1: A 27-year-old woman is brought into the Emergency Department by paramedics. She is very confused and does not know where she is. The paramedics explain that according to witnesses, she was drinking with her friends at a pub, and suddenly dropped to the floor and started “shaking”. Upon further questioning, they describe these movements as the limbs first stiffening, and then jerking. The episode lasted seven minutes. Neurological examination showed no physical abnormalities. What is the most appropriate treatment for this patient's epileptic syndrome? a. Ethosuximide b. Levetiracetam c. Sodium Valproate d. Carbamazepine e. Lamotrigine Answer : E: Lamotrigine This is a classic presentation of a tonic-clonic seizure, with the limbs stiffening and then jerking, in combination with a loss of consciousness as indicated by a sudden drop to the floor. In a woman of child-bearing age, the first line medication is lamotrigine. SBA 2: An 8-year-old boy is brought into his GP by his parents, over “concerns at school.” His mother says that his teacher has noticed that he keeps “slipping in and out.” She has noticed this at home, too, where he stops in the middle of what he was doing or saying, for around ten seconds, and then carries on where he left off. This occurs several times a day. He can never recall these episodes. She is concerned that this is affecting his performance at school. Neurological examination shows no physical abnormalities. What is the most appropriate treatment for this patient's epileptic syndrome? a. Lamotrigine b. Ethosuximide c. Carbamazepine d. Sodium Valproate e. LevetiracetamAnswer: B: Ethosuximide This is a classic presentation of absence seizures: in childhood, consisting of brief pauses several times a day. Ethosuximide is the first-line in absent seizures. SBA 3: A 29-year-old man presents to his GP, complaining of "crazy movements". Upon further questioning, he explains that every now and then, his right arm jerks violently. He mentions that at times, he has thrown cups and plates against the wall, unintentionally. He is completely aware of these episodes and otherwise reports no additional symptoms. Neurological examination shows no physical abnormalities. His GP suspects epilepsy. What is the best description for this patient's symptoms? a. Sodium Valproate b. Topiramate c. Levetiracetam d. Lamotrigine e. Carbamazepine Answer: A: Sodium Valproate This is a classic presentation of myoclonic seizures, where involve a sudden jerking of a limb, trunk, or face. Consciousness is preserved and these movements can be violent and unpredictable. In males, sodium valproate is first-line for myoclonic seizures. SBA 4: An 18-year-old man is reviewed in the clinic with a 3-month history of episodic confusion. He experiences episodes of becoming unaware of his surroundings, during which bystanders report he smacks his lips, plucks his clothes, and does not respond to speech. Each episode is preceded by a feeling of rising in his stomach and lasts for 3 minutes before resolving, after which he feels tired. He has a past medical history of febrile convulsions when he was a child. Given the likely diagnosis, what is the most appropriate first-line treatment option? a. Carbamazepine b. Phenytoin c. Topiramate d. Ethosuximide e. Sodium Valproate Answer: A: Carbamazepine This patient has signs and symptoms consistent with epilepsy characterised by focal seizures emerging in the temporal lobe due to repeated episodes of automatism (lip smacking and plucking), aura (epigastric rising), with impaired awareness with no other apparent underlying cause, followed by a post-ictal period characterised by tiredness. The history of febrile convulsions (seizures provoked by fever in otherwise normal young children which often resolve as children grow up) also supports a diagnosis of epilepsy as it is a risk factor for its development. SBA 5: A 16-year-old girl is rushed to A&E by her parents. She is unconscious and shaking uncontrollably. Her mother says that she has been fitting for over half an hour. What is the most appropriate first step in the management of this patient? a. IV phenytoin b. IV thiopentone c. IV lorazepam/PR diazepam d. Reassure her parents and let the seizure terminate by itself e. Oral sodium valproate Answer: C: IV lorazepam/PR diazepam This patient is in status epilepticus – a seizure lasting longer than 30 minutes or repeated seizures without recovery or regain of consciousness in between. It is a medical emergency and should be treated as soon as a seizure lasts longer than 5 minutes as there can be long- term consequences of waiting until 30 minutes have passed (such as functional impairments due to neuronal injury and death). The patient’s airway should be secured and high-flow oxygen should be administered. ECG, blood pressure and pulse oximetry monitors are attached, blood glucose is measured and IV access is established. A benzodiazepine is then administered in the form of IV lorazepam or PR diazepam (buccal midazolam is also used in the community setting). If the seizure persists, after 10 minutes, they are started on a phenytoin infusion. Blood pressure and ECG are closely monitored because hypotension andarrhythmias are adverse effects of a rapid infusion of IV phenytoin. If the seizure still does not terminate after another 10 minutes, IV thiopentone (general anaesthetic) can be used. VSAQ 1: A 27-year-old woman presents to her GP, complaining of "weird movements". Upon further questioning, she explains that her right leg starts twitching, and this movement moves up her right trunk to involve her right arm. She is completely aware of these episodes and otherwise reports no additional symptoms. Neurological examination shows no physical abnormalities. Her GP suspects epilepsy. What is the best description for this motor phenomenon? Answer: Jacksonian March This motor phenomenon is due to the propagation of electrical activity through the primary motor cortex. VSAQ 2: Maria, an 11-year-old girl, has been rushed to the Children's Assessment Unit with a potential seizure. Her dad filmed the episode and show's you a video in which she has clonic, jerking movements that initially begin in her hand and then move proximally up the arm. In what type of epilepsy is this presentation usually seen? Answer: Frontal lobe seizure Jacksonian movement (clonic movements travelling proximally) indicates frontal lobe epilepsy. VSAQ 3: A 25-year-old woman is reviewed in clinic after experiencing 3 unprovoked episodes of sudden bilateral upper and lower limb limpness and falling. Each episode lasts for 10 seconds and she does not lose consciousness. She denies any incontinence and is able to carry on her activity after a few minutes.Given the likely diagnosis, what is this patient most likely to be started on? Answer: Lamotrigine This patient is likely to have atonic seizures due to experiencing 3 unprovoked episodes of muscle limpness (atony) and falling. Atonic seizures usually last for a few seconds and many patients do not lose consciousness and can return to their activities shortly after. The first- line management for managing atonic seizures in women of childbearing potential is the use of lamotrigine as high-quality evidence has demonstrated its efficacy. For men, the first line is sodium valproate. Sodium valproate must be avoided in women of childbearing potential due to its associations with the development of congenital malformations, therefore, lamotrigine is used in preference for women of childbearing potential. VSAQ 4: A 16-year-old girl presents to the neurology clinic accompanied by her parents. She has been suffering from recurrent falls for the last few months. Her parents describe her falls as sudden, where she seems to lose power in all the muscles in her body and falls to the ground if standing. She never loses consciousness during these episodes and she always remembers them. What is the drug target for the most appropriate management to prescribe? Answer: Voltage-gated Na+ channel The patient in the vignette presents with a classic history of atonic seizures. These seizures are characterised by sudden weakness in all body muscles, short duration and retained awareness. Lamotrigine is recommended as the first-line anti-epileptic for managing atonic seizures in females (of childbearing potential), as sodium valproate is teratogenic by the BNF. The drug target for lamotrigine is voltage-gated Na+ channel. VSAQ 5: A 22-year-old man attends a neurology clinic having been referred by his GP. His initial complaint was excessive twitching and jerks in his arms and legs in the morning. This would be ‘on and off’ for a few seconds after waking. He explained this has happened on 3 or 4 occasions and has never lost consciousness. No one has witnessed any of these events. He reports no history of illicit drug use or previous head trauma. The neurologist decides to start medical treatment. Given the likely diagnosis in this man, what is the drug target for the appropriate treatment to commence?Answer: GABA transaminase This man has experienced myoclonic seizures, seen by the brief-like muscle jerks that occur in clusters shortly after waking. In men, the first-line treatment for myoclonic seizures is sodium valproate. The drug target for sodium valproate is GABA transaminase. SAQ: Part 1: A 17-year-old girl was brought into the emergency department by her mother who 2 hours prior noticed that her child suddenly became limp and fell over. She maintained consciousness and was aware throughout but noticed her eyelid droop and head nod. This lasted a few seconds. The mother believes it was caused by the flashing lights of her eldest son's PS4 console. She decided to bring her daughter into the emergency department as this is the third seizure her daughter has experienced. What would be the most appropriate first-line medication to provide the patient, considering her most likely diagnosis? (1 mark) Answer: Lamotrigine (1 mark) Lamotrigine is considered the first-line management option for female patients experiencing atonic seizures. The patient is showing the typical signs of an atonic seizure including loss of tone but the maintenance of consciousness, with a head nod and eyelid droop. Part 2: How would the first-line management change for male and why? (2 marks) Answer : Sodium valproate would be considered the first line in male patients experiencing atonic seizures. (1 mark) This cannot be given for women of child-bearing age due to the risk of teratogenicity. (1 mark) Part 3: Describe the mechanism of action of the first line drug chosen in part 1. (3 marks)Answer: Lamotrigine blocks voltage-gated Na+ channels on presynaptic glutamatergic neurons. (1 mark) This prevents Na+ influx and hence prevents depolarization of the neurone. (1 mark) This decreases glutamate excitotoxicity. (1 mark) Part 4: She is now started on the combined oral contraceptive pill, but comes back to the GP a few weeks later as she notices that she has been experiencing more seizures than previously. What has likely happened, and what should the GP’s next steps be? (2 marks) Answer: The COCP induces UDPGA which increases lamotrigine metabolism, resulting in less seizure control. (1 mark) Either the dose of lamotrigine should be increased, or the contraceptive changed. (1 mark)