7 Med Epilepsy PDF

Epilepsy Prof Peter Widdess Walsh Consultant Neurologist Beaumont Hospital Learning outcomes: 1. Define epilepsy 2. List the types of epilepsy 3. List the causes/risk factors of epilepsy 4. Describe how each cause leads to the development of epilepsy 5. Outline the common symptoms...

Epilepsy Prof Peter Widdess Walsh Consultant Neurologist Beaumont Hospital Learning outcomes: 1. Define epilepsy 2. List the types of epilepsy 3. List the causes/risk factors of epilepsy 4. Describe how each cause leads to the development of epilepsy 5. Outline the common symptoms and signs of epilepsy 6. Develop a differential diagnosis for epilepsy 7. Outline the overarching principles of investigations and management of epilepsy LEARNING OUTCOME 1 Define epilepsy  What is a seizure? Excessive electrical discharge from the cerebral cortex, resulting in clinical seizure symptoms. Imbalance between excitation and inhibition Symptoms depend on where the seizure is located Epilepsy = recurrent unprovoked seizures  International League Against Epilepsy (ILAE) definition Epilepsy is a heterogeneous disorder of the central nervous system (CNS), characterized by recurrent seizures - at least two, or one in the presence of electrographic (EEG) evidence of epileptiform activity. It is characterized by multiple possible seizure types and syndromes, diverse etiologies, and variable prognoses. Prevalence 1 %, affecting 50 million people in the world, approximately 45,000 people in Ireland. Explanation of new terms ILAE 2017 Onset: Where in the brain the seizure starts from Generalised onset: both sides of the brain involved Focal onset: starts in part (area or lobe) of the brain Unknown onset: unclear where the seizure starts Onset is subdivided by awareness and movement Awareness level: is awareness impaired or not? Motor or non motor: is movement involved or not? Terminology Seizure: a sudden change in behavior caused by electrical hypersynchronization of neuronal networks in the cerebral cortex. Unprovoked seizure: refers to a seizure of unknown etiology as well as one that occurs in relation to a preexisting brain lesion or progressive nervous system disorder. Unprovoked seizures that are determined to be due to an underlying brain lesion or disorder are also referred to as remote symptomatic seizures. They carry a higher risk of future epilepsy compared with acute symptomatic seizures. Provoked seizures: occur in the context of systemic processes such as drug and alcohol intoxication/withdrawal, acute brain injury, metabolic disturbances or eclampsia. In these settings seizures may not imply a future risk of developing epilepsy. Harry Lee Parker ▪ “And so today you have seen two extremes of epilepsy. In the first case the disease is one I call a malignant type. It has worsened steadily and remorselessly since the first minor attack, and will continue to get worse. Despite all our more modern remedies, medication has failed, and the patient is a total loss to society and a misery to himself. The second patient has what one certainly would call a benign type of epilepsy, easily controlled by medication, and for all I know, she might have recovered without any treatment…….There is no rule in epilepsy that cannot be broken; it is largely an unpredictable disease except for general experience and all the aids to diagnosis and prognosis we can get”. ▪ Clinical Studies in Neurology 1946 Todd’s Paralysis – Robert Bentley Todd ▪ “A paralytic state remains sometimes after the epileptic convulsion. This is more particularly the case when the convulsion has affected only one side or one limb: that limb or limbs will remain paralytic for some hours, or even days, after cessation of the paroxysm, but it will ultimately perfectly recover”. Department of Medicine, RCSI Epidemiology ▪ A national lifetime prevalence of self-reported epilepsy among adults of 10 per 1,000 population. ▪ A national prevalence of treated epilepsy in Ireland 9 per 1,000 (2005) for those over the >5 years. ▪ An average of 13 patients with epilepsy presenting to each GP nationwide. ▪ An average of 17 hospital-based consultations for epilepsy each week per Consultant Neurologist, ▪ and therefore approximately 442 consultations nationwide. ▪ An estimated 67 discharges of persons with epilepsy occurring weekly in acute hospitals in Ireland. Department of Medicine, SUMMARY REPORT. May 2009. Brainwave RCSI The Irish Epilepsy Association LEARNING OUTCOME 2 List the types of epilepsy  Classification A) By mode of onset: B) By AETIOLOGY 1) Genetic: including epilepsy syndromes 2) Structural: congenital or acquired 3) Metabolic 4) Immune 5) Infectious 6) Unknown: Nature of underlying cause not currently known. C) Epilepsy syndromes Complex clinical features, signs and symptoms that define a distinctive, recognisable clinical seizure disorder. Can be focal/generalised Usually identified based on age of onset, seizure type(s), EEG characteristics, aetiologies and associated comorbidites. Now many recognised to be due to specific pathogenic gene mutations Examples Syndromes Genes Autosomal dominant nocturnal frontal lobe epilepsy (NFLE) CHRNA2 Autosomal dominant epilepsy with auditory features LGI1 Juvenile myoclonic Epilepsy Complex Childhood Absence Epilepsy Complex Dravet syndrome SCN1A, epileptic encephalopathy Lennox-Gastaut syndrome Various de novo mutations, ie DNM1, SLC6A1 LEARNING OUTCOME 3 List the causes/risk factors of epilepsy Causes and risk factors Acute symptomatic seizures (provoked seizures) Acute hemorrhagic and ischemic stroke Metabolic encephalopathy Drugs and alcohol Others (eg, recent head trauma, active intracranial infections) Epilepsy (unprovoked seizures) Cerebrovascular disease (eg, prior stroke, vascular malformation) Dementia Others (eg, brain tumors, remote head trauma, prior intracranial infection) Unknown Seizure triggers and risk factors Lack of sleep Alcohol abuse Drugs – missed dose; starting a new medication due to interactions with anti- seizure-medication (ASM) Stress Acute illnesses and fever Dehydration Head injury Stroke Flashing lights – 3-5% of all epilepsies are photosensitive Loud noise or music (reflex epilepsy) LEARNING OUTCOME 4 Describe how each cause leads to the development of epilepsy  Seizures and epilepsy are the consequence of an imbalance between excitation and inhibition within certain regions of the central nervous system which arise from hyperexcitation and hypersynchronisation of a neuronal network. This may be a result of hypoxia, alkalosis, hypoglycemia and abnormal neurotransmitter properties, which release large amounts of neurotransmitters at the synapse and consequently promote seizure. The neurons in the epileptogenic focus have a lower threshold for stimulation and therefore are hyperexcitable. The irritable neurons are easily activated by any physiological changes and certain conditions such as fatigue or lack of sleep, stress, fever and constipation may lower the threshold for seizures. The focal cells stimulate the nearby normal cells leading to the spread of the activity Clinical presentation Features that suggest seizure in older adults: Confusion, behavioral change, or unresponsiveness Sudden falls with no recall or warning Recurrent events occurring in various positions or circumstances Arousal from sleep with confusion or disorientation Seizures in older adults are often difficult to recognize for the following reasons: Lack of aura or preceding warning Lack of motor features Comorbid dementia Misdiagnosis as delirium LEARNING OUTCOME 5 Outline the common symptoms and signs of epilepsy Clinical features Before & during the seizure: Aura (sensory, motor, autonomic features) Loss of consciousness Motor: tonic/clonic movements of the face and extremities – one limb/bilateral Urinary incontinence Tongue biting Eyes: rolling, open, eyelids flickering Head turning After the event: Confusion Poor coordination Signs of tongue biting Focal weakness – “Todd’s paralysis” Hedadache Deep sleep Clinical manifestation of tonic-clonic seizure LEARNING OUTCOME 6 Develop a differential diagnosis for epilepsy Differential diagnosis/seizure mimics Hypoglycaemia Syncope – cardiogenic in elderly with high morbidity and mortality. Hypotension mimicking postictal state Delirium and confusional states Non-epileptic attack disorder (NEAD) – diagnosed by in-patient video EEG monitoring Transient ischemic attacks Transient global amnesia Sudden unexplained falls/drop attacks Psychogenic spells and/or behavioural spells Sleep disorders Migraine Movement disorders: paroxysmal dystonias LEARNING OUTCOME 7 Outline the overarching principles of investigations and management of epilepsy Diagnosis Eye-witness description of the event is VITAL! Clinical diagnosis – history is key in the diagnosis. Rule out causes of provoked seizures first - ask about triggers: recent illness, drug/alcohol use etc. Look for medical alerts (bracelets etc) Establish whether know epileptic or not at the beginning of the consultation. If known epileptic, ask about compliance with medication, frequency, duration of seizures, recent dose adjustment of ASM. Diagnostic tests BLS – hypoglycaemia can mimic a seizure ECG to rule out underlying arrhythmia Check electrolytes – Na, K, Mg, Ca, U&E. Lactate level – commonly elevated during/after seizures FBC, CRP for infection MSU for dipstick and HCG – pre-eclampsia can lead to eclampsia and seizures Urinary toxicology Sputum/wound swab CT in emergency and pre-LP MRI brain (more sensitive) looking for alternative diagnosis (less widely available in acute setting) LP in meningitis and subarachnoid haemorrhage (perform CT prior LP) Tilt-table testing  Investigations Neuroimaging- in all adults with first seizure and should be performed immediately when an intracranial lesion is suspected (non-contrast CT Brain followed by MRI in these cases) EEG Positive finding: Generalized epileptiform activity or focal, localizing abnormality Can be used to support the diagnosis of idiopathic generalized or focal-onset epilepsy A normal EEG does NOT exclude epilepsy Only 25% approximately will be abnormal at presentation with first seizure Provocation testing may be used to increase yield Sleep deprivation Hyperventilation/Photic stimulation Gold standard: Inpatient video-EEG monitoring LP: Suspected intracranial infection or inflammatory disease Metabolic/Genetic studies Status epilepticus Prolonged seizure lasting over 5 minutes, or a series of seizures with incomplete recovery of consciousness. (MEDICAL EMERGENCY) Incidence 20 - 40 / 100 000 per year Half of these patients have acute symptomatic (metabolic/structural) cause If a seizure lasts longer than 5 minutes it should be treated as a medical emergency and this is why we give a “5 minute rule” for calling an ambulance. Emergency medication helps prevent Status Epilepticus. Emergency management: 1st line: benzodiazepines: diazepam PR, Midazolam buccal, Lorazepam IV Repeat dose of benzodiazepine if seizure does not stop within 5 – 10 mins. Seek expert help. 2nd line: Levetiracetam IV, Phenytoin IV (loading dose), Valproate IV 3rd line: Phenobarbital and Propofol infusion; general anaesthesia. Support ABC’s – oxygen via non-rebreather mask, left lateral position to reduced the risk of aspiration  1 2 3 4 5 6 7 8 A 37-year-old female , is brought into emergency department be ambulance following a collapse. She is currently having a generalized seizure while lying on a bed. The ambulance crew managed to place a cannula and ask if you want 3 PLANNING to give any medication. They report that she has been seizing for about 10 MANAGEMENT minutes. She is not on any regular medications, and has never had a seizure before Which of the following medication will be the first to be given patient ? A. IV Lorazepam B. Sublingual Nitrate C. IV Levetiracetam D. IV Flumazenil E. Propofol infusion A Correct Answer:1st line management for Seizures is benzodiazepines: diazepam PR, Midazolam buccal, Lorazepam IV Non-convulsive status epilepticus Most commonly in critically ill patients in the hospital (ICU) setting. It affects up to 10 % of the patients with reduced level of consciousness. Can be diagnosed on EEG.  Beaumont Hospital Status epilepticus protocol Management of Convulsive Status Epilepticus in Adults Time Line Stabilise the patient. Secure airway and give oxygen. Assess cardiac and respiratory function 0-5 min Assess blood glucose – correct any hypoglycaemia with glucose Stabilisation Time seizure from its onset. Phase Establish intravenous access if possible. Take blood for FBC, Renal, Liver and Bone profile and Anti-epileptic drugs levels Initial therapy: Give Benzodiazepine IV Lorazepam 0.1mg / kg. (Maximum 4 mg per dose) Administer 2mg/min. Dilute with equal volume of normal saline prior to IV administration. If no IV access available, consider buccal midazolam 10mg. Eclampsia in Pregnancy: Contact neurology for advice. Commence treatment with 4g Magnesium Sulphate intravenously over 5 to 15 minutes, followed by maintenance of 1 g/hour maintained for 24 hours Repeat IV Lorazepam 0.1mg / kg (Maximum 4 mg per dose) 5-10 min Initial Therapy If no IV access available give IM midazolam 10mg Phase Patients weighing less than 40kg and elderly patients give IM midazolam 5mg or Consider buccal midazolam 10mg Prepare Levetiracetam or Phenytoin for infusion if needed If still seizing Call Neurology Give Second therapy: IV Levetiracetam or Phenytoin Levetiracetam 60mg / kg, max. 4.5g, IV infusion in 100mls Normal Saline over 15 minutes Phenytoin* 20mg / kg (Max 2g). Infuse in normal saline using a 0.2 micron filter Dose Volume of Normal Saline Up to 1g 100ml 10-20 min Greater than 1g 250ml Second Therapy Max rate = 50mg/min Phase Cardiac monitoring required during and after infusion. Saline flush after. *Other second line options are IV sodium valproate 40mg / kg (max 3g) or IV lacosamide 200mg If still seizing Call ICU/Anaesthesia If there is ongoing seizure activity despite above measures. 20-60 min Third Therapy Contact ICU for further management for consideration of infusions Phase of midazolam, propofol or barbiturate agents. References: Evidence-based guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the guideline Committee of the American Epilepsy Society. Epilepsy Currents, Vol 16, No. 1 2016 48-61 BNF Online. https://www.formularycomplete.com/. Accessed June 2020 Epanutin SPC Accessed via www.medicines.ie Jones S, Pahl C, Trinka E, et al. A protocol for the inhospital emergency drug treatment of convulsive status epilepticus in adults. Pract Neurol 2014;14:194-197 Kapur J, et al Randomized Trial of Three anticonvulsant medications for status epilepticus. NEJM 2019;381:2103-2113 Hypertension in pregnancy: diagnosis and management NICE guideline [NG133] If still seizing after 10mins  Chronic Treatment with Anti-epileptic drugs Usually not necessary after a single seizure, particularly if provoked by factors that resolve Should be started in patients at significant risk for recurrent seizures Generally started after ≥ 2 unprovoked seizures started After 1 seizure if has the following: ✓ Epileptiform abnormalities on interictal EEG ✓ Remote symptomatic cause as identified by clinical history or neuroimaging (eg brain tumour, brain malformation, prior CNS infection) ✓ Abnormal neurologic examination ✓ First seizure that occurs during sleep Patient education Side effects of medications Management of triggers: sleep hygiene, alcohol, compliance Counselled about unsupervised activities that might pose danger with sudden LOC e.g. working at heights/ machinery/ hot surfaces/ swimming alone etc. SUDEP (sudden unexplained death in epilepsy) Driving: (NDLS Ireland) Epilepsy: Group 1 drivers (car/motorcycle/tractor): stop driving until seizure free for a year First unprovoked seizure: G1 drivers: minimum seizure-free period before driving: 6/12, not to resume driving until treating consultant is satisfied that medical results shows that patient is medically fit to drive Treatment of Epilepsy General approach – Ideally use one drug appropriate to diagnosis – About 2/3 new diagnoses of epilepsy are successfully treated with first antiseizure drug – Goal is “no seizures and no side effects” Increase dose as tolerated Rational polytherapy Considerations – Interactions with other medications – Co-morbid medical conditions – renal, hepatic disease, etc. – Older patients – Women of childbearing age/pregnancy – Lifestyle and patient preferences – Cost Other Treatment Options Epilepsy surgery Vagal nerve stimulation/Devices Dietary therapies Surgery May be considered for patients with seizures that are poorly controlled on medical treatment Should have clearly defined focus Especially helpful for seizures from structural abnormalities Has the potential to cure certain forms of epilepsy and improve quality of life Future developments Newer drugs Parenteral formulations Direct comparison trials Cost considerations Pharmacogenetics Laser surgery Neurostimulation Precision Medicine Cases Interactive problem-solving examples of common epilepsy syndromes Case 1 16yo Morning jerks Daydreaming spell in class Late night/beer – GTC Epilepsy Epilepsy type Generalized Seizure type Myoclonic/Absence/GTC Cause Genetic Co-morbidity Migraine Case 2 29yo Febrile seizures as infant Déjà vu/fear aura then lip smacking GTC from sleep Epilepsy Epilepsy type focal Seizure type Psychic aura – automatism/unware – GTC Cause Mesial temporal sclerosis Co-morbidities Memory loss, depression Case 3 45yo Intellectual disability/autism Episodes stiffening/incontinence at night, other episodes unaware, restless, agitated after, other drops to ground Epilepsy Epilepsy type: generalized and focal Seizure type: generalized tonic, atypical absence, atonic seizures Cause: unknown, DNM1 mutation Co-morbidities: ID  Case 4 6yo Zoning out many times a day Not keeping up in school Eye flutter/activity arrest Epilepsy Epilepsy type: generalized Seizure type: typical absence Cause: genetic Co-morbidities: ADHD  Case 5 78yo Left frontal stroke 18 months ago Episodes right arm jerking and confusion Epilepsy Epilepsy type: focal Seizure type: Right arm clonic seizure Cause: Stroke (post-stroke epilepsy) Co-morbidities: right hemiparesis