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&QJMFQTZ Name: Kirsty Genfi Email: kirsty.genfi21@imperial.ac.ukStructure The 7 step process Seizure definition and Classification Seizure management Interictal Epileptiform Discharges Questions0#+&$5*7&4▯0'▯."/"(&.&/5▯ ‘The 7 Step Process’: 1. Identify the patient’s problem Epilepsy Identify which type 2. Specify the therapeutic objective Eliminate seizures Avoid adverse effects Maintain a normal lifestyle 3. Select a drug on the basis of comparative efficacy, safety, cost and suitability Lamotrigine Sodium Valproate Diazepam Levetiracetam Also: Carbamazepine, topiramate, ethosuximide, phenytoin1IBSNBDPMPHZ▯PG▯&QJMFQTZ&QJMFQTZ • Seizures: sudden bursts of electrical activity in the brain causing changes in muscle tone, behavioural awareness • Epilepsy Syndromes: characterised by repeated seizures • Diagnosed with EEGs (seizure type) and MRI (organic causes) • Triggers: • Poor sleep • Alcohol and drugs (and their withdrawal) • Stroke • Intracranial haemorrhage • Space-occupying lesions • Metabolic disturbances4FJ[VSF▯$MBTTJGJDBUJPO • Classification: • Loca on in the brain: generalised (affects both sides of the brain from the start) or focal (just one side of the brain). • Level of consciousness • Involvement of motor symptoms • Two main types: • Focal • Generalised'PDBM▯4FJ[VSFT • With impairment of consciousness ('complex’): • Patients lose consciousness either after an aura, or at seizure onset. • Most commonly originate at the temporal lobe. • Post-ictal symptoms are common (eg. confusion). • Without impairment of consciousness ('simple’): • Patients do not lose consciousness, and only experience focal symptoms. • Post-ictal symptoms do not occur. • Evolving to a bilateral, convulsive seizure ('secondary generalised’): • Focal seizure then evolves to a generalised seizure (typically tonic-clonic). • In 2/3 of patients with focal seizures. 'PDBM▯4FJ[VSFT▯ TZNQUPNT Parietal lobe Frontal lobe Sensory symptoms such as tingling Motor features such as and numbness; motor symptoms - Jacksonian features, due to spread of electrical activity to dysphasia, or Todd's the pre-central gyrus in the frontal palsy. lobe. Occipital lobe Visual symptoms such as spots and lines in the visual field. Treatment of focal seizures Carbamazepine (SE: SIADH, drowsiness, diplopia, ataxia) or Temporal lobe Lamotrigine (SE: rash, tremor, Automatisms (eg. lip-smacking); diplopia) is first-line déja vu or jamais vu, emotional disturbance (eg. sudden terror); hallucinations.atory, or auditory(FOFSBMJTFE 4FJ[VSFT • Absence seizures • Often children • Pause briefly, for less than 10 seconds, and then carry on where they left off. • Treatment: Sodium Valproate or Ethosuximide is first-line; avoid Carbamazepine. • Tonic-clonic seizures • Patients lose consciousness; their limbs stiffen (tonic) and start jerking (clonic). • Post-ictal confusion is common. • Treatment: Sodium Valproate or Lamotrigine is first-line. • Myoclonic seizures • Sudden jerk of a limb, trunk, or face. • Treatment: Sodium Valproate or Levetiracetam (or Topiramate) is first-line; avoid Carbamazepine. • Atonic seizures • Sudden loss of muscle tone, causing the patient to fall, whilst retaining consciousness. • Treatment: Sodium Valproate or Lamotrigine is first-line.$PNQMJDBUJPOT▯PG▯&QJMFQTZ • Status epilepticus • 30 minutes of continuous seizures • work and call the anaesthetist Midazolam/rectal Diazepam, then Phenytoin if that does not • Depression • Suicide • Sudden unexpected death in epilepsy (SUDEP) • Thought to be due to excessive electrical activity causing a cardiac arrhythmia and death..BOBHFNFOU▯PG▯&QJMFQTZ • The focus of drug therapy in epilepsy is optimisation of quality of life with control of seizure activity, but any treatment must be balanced against potential side effects. • General rules of thumb: • Lamotrigine, levetiracetam and valproate are good for all seizure types. • Carbamazepine, gabapentin and phenytoin are better for focal (including secondary generalised) seizures. • Ethosuximide is the drug of choice for absence seizures. • Carbamazepine may worsen myoclonic seizures. • Interactions with other medications, e.g. phenytoin and carbamazepine, to be considered. • Teratogenicity – sodium valproate has a high risk of neural tube defects. • Lamotrigine is a good choice for women of childbearing age.4#"▯▯▯ A 26 year old man suffers a blackout and is brought to the emergency department by ambulance. He is accompanied by a friend who describes sudden collapse followed by 2-3 minutes of violent jerking with his eyes open. He also reports that his friend had described a strange feeling in his stomach and disturbed sense of taste as they sat eating together prior to the onset of the event. On examination, the man is drowsy and confused. There are subtle abrasions on the lateral aspect of his tongue, but no evidence of incontinence or residual neurological deficit. What is the single most likely diagnosis? A. Vasovagal syncope B. Stokes-Adams attack (arrhythmogenic syncope) C. Seizure D. Pseudoseizure (psychogenic non-epileptic attack) E. Anxiety attack4#"▯▯▯▯ "/48&3▯ A 26 year old man suffers a blackout and is brought to the emergency department by ambulance. He is accompanied by a friend who describes sudden collapse followed by 2-3 minutes of violent jerking with his eyes open. He also reports that his friend had described a strange feeling in his stomach and disturbed sense of taste as they sat eating together prior to the onset of the event. On examination, the man is drowsy and confused. There are subtle abrasions on the lateral aspect of his tongue, but no evidence of incontinence or residual neurological deficit. What is the single most likely diagnosis? A. Vasovagal syncope B. Stokes-Adams attack (arrhythmogenic syncope) C. Seizure D. Pseudoseizure (psychogenic non-epileptic attack) E. Anxiety attack4#"▯▯▯ Whilst eating dinner with his family, an 11-year-old boy suddenly drops his cutlery and begins to stare blankly into space. His eyelids begin to flutter, his eyes roll upwards and this continues for 10 seconds. His dad notices the event and asks him about it, but he can’t remember what happened. What type of seizure is this describing? A. Absence B. Simple partial C. Complex partial D. Myoclonic E. Atonic4#"▯▯▯▯ "/48&3▯ Whilst eating dinner with his family, an 11-year-old boy suddenly drops his cutlery and begins to stare blankly into space. His eyelids begin to flutter, his eyes roll upwards and this continues for 10 seconds. His dad notices the event and asks him about it, but he can’t remember what happened. What type of seizure is this describing? A. Absence B. Simple partial C. Complex partial D. Myoclonic E. Atonic1IBSNBDPMPHZ▯PG▯&QJMFQTZ • How to approach the question: • What is the first line drug? • Is this drug appropriate for this patient?-BNPUSJHJOF • Mechanism of Action • Blocks Voltage-gated Na+ channel on presynaptic glutamatergic neurons • Prevents Na+ influx Lamotrigine • Prevents depolarization • ↓ glutamate excitotoxicity • Drug-drug interactions Na+ VG Na+ channel • COCP induces UDPGA • ↑ lamotrigine metabolism • Less seizure control • Side effects • Maculo-papular rash (10%) • Drowsiness Na • Steven-Johnson’s syndrome (1 in 1000) • Suicidal thoughts (rare) 4PEJVN▯7BMQSPBUF • Mechanism of Action 1.Inhibits GABAtransaminase (enzyme) inside presynaptic GABAergic neurons and non-neuronal cells →prevents breakdown of GABA: a)Directly ↑ GABAconcentrations in synapse (presynaptically) b)Indirectly prolongs GABAin synapse ∵↓ extraneuronal metabolism of GABA→slower removal of GABAfrom synapse Valproate 2.↑ GABAavailability →inhibitory activity on postsynaptic neurons (GABAAreceptor) • Drug-drug interactions • Broad CYP450 enzyme inhibitor ∴ most other co-admin drugs need reduced doses • Avoid before conception, during pregnancy & breastfeeding • Side effects • GI: Nausea, abdominal pain, diarrhoea • Drowsiness, weight gain, hair loss • Hepatotoxicity, teratogenicity, pancreatitisValproate 4PEJVN▯7BMQSPBUF • Mechanism of Action 1.Inhibits GABAtransaminase (enzyme) inside presynaptic GABAergic neurons and non-neuronal cells →prevents breakdown of GABA: a)Directly ↑ GABAconcentrations in synapse (presynaptically) b)Indirectly prolongs GABAin synapse ∵↓ extraneuronal metabolism of GABA→slower removal of GABAfrom synapse Valproate 2.↑ GABAavailability →inhibitory activity on postsynaptic neurons (GABAAreceptor) • Drug-drug interactions • Broad CYP450 enzyme inhibitor ∴ most other co-admin drugs need reduced doses • Avoid before conception, during pregnancy & breastfeeding • Side effects • GI: Nausea, abdominal pain, diarrhoea • Drowsiness, weight gain, hair loss • Hepatotoxicity, teratogenicity, pancreatitis%JB[FQBN • Mechanism of Action postsynaptic neuronsptor) via benzodiazepine site on 2. ↑ Cl-ion influx → hyperpolarisation of excitatory neurons • Therapeutic use: • Status epilepticus • Chlordiazepoxide given for alcohol withdrawal • Sedation effects/short term for anxiety • Side effects • Drowsiness • Respiratory depression (IV or ↑ dose) • Haemolytic anaemia, jaundiceValproate%JB[FQBN • Mechanism of Action postsynaptic neuronsptor) via benzodiazepine site on 2. ↑ Cl-ion influx → hyperpolarisation of excitatory neurons • Therapeutic use: • Status epilepticus • Chlordiazepoxide given for alcohol withdrawal • Sedation effects/short term for anxiety • Side effects • Drowsiness • Respiratory depression (IV or ↑ dose) • Haemolytic anaemia, jaundice-FWFUJSBDFUBN • Mechanism of Action • Inhibits SV2Aon excitatory presynaptic neuronal vesicles • Prevents vesicle exocytosis • ↓ Glutamate secretion presynaptically • ↓ Glutamate excitotoxicity • Drug-drug interactions • None –no CYP450 enzyme interaction • Requires good renal function • Side effects • Dizziness, headache • Somnolence • Fatigue0UIFS▯1PJOUT▯GSPN▯*OTFOEJ • EEG shows interictal epileptiform discharge (IED) – risk of seizure recurrence4#"▯▯▯ 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. Myoclonic seizure B. Cortico-basal degeneration C. Atonic seizure D. Tonic-clonic seizure E. Reflex anoxic seizure4#"▯▯▯▯ "/48&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. Myoclonic seizure B. Cortico-basal degeneration C. Atonic seizure D. Tonic-clonic seizure E. Reflex anoxic seizure4#"▯▯▯ A 28 year old lady has been newly diagnosed with epilepsy, describing her seizures as muscle stiffening then jerking while unconscious, lasting 3m. She is not on the COCP and is currently trying for children. Which anti-epileptic medication is appropriate for her? A. Diazepam B. Sodium Valproate C. Lamotrigine D. Ethosuximide E. Levetiracetam4#"▯▯▯ A 28 year old lady has been newly diagnosed with epilepsy, describing her seizures as muscle stiffening then jerking while unconscious, lasting 3m. She is not on the COCP and is currently trying for children. Which anti-epileptic medication is appropriate for her? A. Diazepam B. Sodium Valproate C. Lamotrigine D. Ethosuximide E. Levetiracetam4#"▯▯▯ A 25-year-old man is seen in clinic with 5 unprovoked episodes of rapid bilateral upper and lower limb muscle contraction and relaxation that last around 10 seconds before stopping. These episodes cause him to fall to the floor; however, he denies any loss of consciousness and is able to continue doing his activities after. A collateral history is taken, and it is established that no incontinence or tongue biting occurs. Given the likely diagnosis, what is this patient most likely to be started on? A. Ethosuxamide B. Lamotrigine C. Levetiracetam D. Sodium Valproate E. Topiramate4#"▯▯▯ A 25-year-old man is seen in clinic with 5 unprovoked episodes of rapid bilateral upper and lower limb muscle contraction and relaxation that last around 10 seconds before stopping. These episodes cause him to fall to the floor; however, he denies any loss of consciousness and is able to continue doing his activities after. A collateral history is taken, and it is established that no incontinence or tongue biting occurs. Given the likely diagnosis, what is this patient most likely to be started on? A. Ethosuxamide B. Lamotrigine C. Levetiracetam D. Sodium Valproate E. Topiramate46.."3:▯ Focal Seizure Absent Seizure • Specific focal symptoms • Child, blank stare for 10s • Carbamazepine • Ethosuxamide Other 3 Generalised Seizures Status Epilepticus • Tonic-clonic, Myoclonic, Atonic • Lasting >30mins without regaining consciousness • Males = sodium valproate • Females = lamotrigine or leveracitam • Benezodiazepams5)"/,▯:06▯ Please fill in the Feedback form! Name: Kirsty Genfi Email: kirsty.genfi21@imperial.ac.uk https://app.medall.org/feedback/feedback- flow?keyword=c28516da3a4bda1b72d43278&organisation=imp erial-pharmacology-society