Epilepsy Study Guides

Epilepsy    Occurrence of 2 or more unprovoked seizures (without knowing underlying cause). Seizure is a paroxysmal event due to abnormal excessive or synchronous neuronal activity in the brain. The abnormal brain activity may result in dramatic convulsive activity or milder neurologic problems. Epidemiology  5 – 10% of population will have one seizure, only 0.3 – 0.5% of population go on to develop epilepsy.  Prevalence in Australia is over 225, 000 Australians; 3 – 3.5% of Australians will experience epilepsy at some point in their lives.  ~25, 000 people in Australia are diagnosed with epilepsy each other.  An estimated 2.4 million new cases occur each year globally.  Up to 70% of people gain full seizure control with treatment. Abnormal neural activity  Neuronal excitability is marked by action potential.  Hyperexcitability can be caused by: o Increased excitatory transmission: glutamate, aspartate. o Decreased inhibitor transmission: GABA.  There is alteration in ion channels and electrolyte concentrations.  Abnormal neural activity can be caused by: o Trauma. o Strokes. o Infection (e.g. meningitis, encephalitis). o Inflammation (e.g. vasculitis). o Degeneration (e.g. dementia). o Growths (e.g. benign meningioma, malignant glioblastoma).  During embryonic development: o Birth trauma. o Perinatal/intrauterine infections. o Vaccinations?? o Cortical dysplasia, abnormal embryonic development.  Environmental risk factors: o Reflex epilepsy: light, music, reading, hot water. o Metabolic and endocrine disorders. o Alcohol or alcohol withdrawal. o Other drugs and toxins.  Genetic causes: o Mutations in SCN1A caused generalised epilepsy with febrile seizures. o Mutations in DEPDC5 cause familial focal epilepsy with variable foci. Classification of seizures  Generalised seizures: involving generalised hyperactivity.  Partial/focal seizures: focal onset of seizure activity. o Frontal lobe: motor and pre-motor areas. o Parietal lobe: primarily sensory areas. o Temporal lobe: memory (but more likely sensory). o Can lead to secondary generalised seizure if affecting enough areas. Generalised seizures  Characterised by a sudden cry and fall, followed by: o Convulsive movements of all limbs. o Shallow/interrupted breathing, possibly leading to cyanosis. o Loss of bowel/bladder control. o Slow return to consciousness, post-seizure confusion and/or fatigue  Tonic-clonic: begins with stiffening, followed by rhythmic jerking of all limbs.  Tonic: abrupt stiffness and loss of consciousness.  Clonic: jerking of muscles.  Absence: brief loss of awareness, staring with some automatisms.  Myoclonic: brief jerking or twitching in limbs or trunk.  Akinetic/atonic: loss of muscle tone generally resulting in falls. Simple partial seizure  Seizure activity in the brain causing: o Rhythmic movements: isolated twitching of arms, face, legs. o Sensory symptoms: tingling, weakness, sounds, smells, tastes, visual distortions, feeling of upset stomach. o Psychic symptoms: déjà vu, hallucinations, feelings of fear or anxiety.  Usually last less than one minute.  May precede a generalised seizure. Classification of epilepsy  Idiopathic: genetic.  Secondary structural cause.  Cryptogenic: unknown. Epilepsy syndromes  Depends on: o Family history. o Age of onset of the condition. o Seizure type(s). o Cause, and other underlying diseases/conditions. o Rate of progression or development over time. o Presence or absence of neurologic abnormalities. o Investigation findings. o Response to medication.  Juvenile myoclonic epilepsy: o Onset in teens. o Three kinds of seizures; generalised tonic-clonic, absence and myoclonic jerks. o Respond well to treatment. o May need life-long treatment. o Remote family history. Clinical correlation: patient information on seizure  Patient has had a seizure, what do you do? o Ascertain detailed history. o General examination. o Examine neurological system. o Look for trigger or provoking factors. o Exclude mimics. o Ascertain family history.  Need to rule out mimics: o Faint or syncope. o Panic attacks. o o o o o o     Cardiac disorders. Hypoglycaemia. Abnormal involuntary movements (e.g. chorea and tics). Migraines. Sleep phenomena or parasomnia. Non-epileptic seizures or pseudo-seizures. Ascertained that it was a seizure, what do you do tell your patient? o They have had a seizure (i.e. abnormal brain activity). o There is <10% chance of second seizure. o If second seizure occurs, they are likely to have epilepsy and require treatment. Recommendation to patients: o Aim of treatment would be control, not cure seizures. o Treatment aims at maintaining and returning to normal lifestyle and activities. o Medications. o Avoid provoking factors and seizure threshold reducing agents. Recommendation to patient’s family: Increased risk of death may be related to: o An underlying brain disease, such as tumour or infection. o Seizures in dangerous circumstances, leading to drowning, burns or head injury. o Prolonged or ongoing seizures (status eplepticus). o Sudden and unexplained causes (SUDEP). o Possible respiratory or cardio-respiratory arrest during seizure. o Suicide. Clinical tests  Blood tests. o Exclude infections. o Look for electrolyte abnormalities. o Renal and hepatic dysfunction. o Ca2+, Mg2+, phosphates important (hypercalcaemia can cause seizure). o Urinary and chest infections. o Think of metabolic conditions if history suggestive. o Mitochondrial problems: test serum lactate, pyruvate.   Electroencephalogram (EEG). o Recording of electrical activity in the brain. o Generally scalp recording, but occasionally intracranial recording (particularly during surgery). Imaging. o CT scans (for bleeds) and MRI scans. Medications Antiepileptic drug Primidone, barbiturates. Carbamazepine, iamotrigine. Ethuosuximide. Phenytoin. Valproate.      Mechanism of action Enhances GABAerggic inhibition. Inhibits voltage-dependent Na+ channels, resulting in decreased release of excitatory transmitters. Modifies low-threshold or transient Ca2+ currents. Blocks Na+ dependent action potentials; reduces neuronal Ca2+ uptake. Reduces high-frequency neuronal firing and Na+ dependent action potentials; enhances GABA. Start with initial small dose. Titrate gradually (or rapidly if increased seizures) until ideal dose achieved. Measure blood levels. Watch for adverse side effects: o May be related to dose. o Care must be taken in discontinuing drug due to risk of seizure recurrence. Most common side effects: o Rash. o Clumsiness. o Drowsiness.    o Irritability. o Nausea. Warning signs of possible serious side effects: o Prolonged fever. o Rash, nausea/vomiting. o Severe sore throat. o Mouth ulcers. o Easy bruising. o Pinpoint bleeding. o Weakness. o Fatigue. o Swollen glands. o Lack of appetite. o Abdominal pain. When choosing medication, consider: o Type of seizures. o Contraindications. o Likely side effects. o Time needed to reach a therapeutic level. o Frequency of dosing. o Forms available. o Drug interactions. o Pregnancy and teratogenicity (do not use valproate if pregnant; causes low IQ). Factors that influence response to medications: o Consistent use. o Inadequate dose or ineffective medication. o Drug factors. o Disease. Seizures markedly reduced; 30% Seizures do not respond; 20% Alternative therapy Seizures eliminated; 50%     Other options include vagus nerve stimulation and ketogenic diet. A small percentage of people may be eligible for surgery; 70% of people who have epilepsy surgery become seizure free. Up to 15% of people referred to an epilepsy specialist centre do not actually have epilepsy and have been previously misdiagnosed. Many people outgrow or have a long term remission from seizures. Ketogenic diet  High fat, adequate protein, low carb diet.  GLUT1 deficiency syndrome leads to epilepsy.  Classic phenotype: o Infantile-onset seizures. o Delayed neurologic development. o Acquired microcephaly. o Complex movement disorders. o 5 seizures types occur: generalised tonic or clonic, myoclonic, atypical absence, atonic and unclassified. Vagus nerve stimulation  Designed to prevent seizures by sending regular, mild pulses of electrical energy to the brain via the vagus nerve. o Used together with medication (i.e. does not replace medication).  The VNS device is sometimes referred to as “pacemaker for the brain”. o Placed under the skin on the chest wall. o Controlled with hand held magnet.  Reduces seizure severity, frequency an duration by ~50%. Epilepsy surgery  For those with intractable epilepsy.  Crucial to select appropriate candidate.  Delineate epileptogenic zone with EEG and PET.  Possible procedures include: o Lobe resection. o Corpus callosotomy. o Lesionectomy. o Functional hemispherectomy. o Multiple subpial resection. Clinical correlation: status epilepticus  Either continuous seizure activity for 30 minutes or repeated seizures without full recovery of consciousness between attacks.  May be generalised or partial (complex partial or simple partial).  It is a medical emergency.  Start treatment after 5 minutes from when seizure started (even though not sure if it is status epilepticus).         Protect the airway and maintain oxygenation. Administer one type of medication, as listed below. Diazepam: o 10 – 20mg over 2 – 5 minutes, not exceeding 5mg/min. o Repeat once 15 minutes later if seizures continue. Midazolam: o 5 – 10mg (IM or IV) over 2 – 5 minutes. o Repeat once 15 minutes later if seizures continue. Phenytoin: o 15 – 20mg/kg (IV), not exceeding 50mg/min. o Continue monitoring ECG and BP. Sodium valproate: o 10mg/kg (slow IV), up to 800mg. o Usually followed by continuous infusion of 1 – 2mg/kg/hour to a maximum of 2500mg/day according to response. Transfer to ICU, where an infusion of midazolam, propofol or thiopentone may be used. Investigate for cause. Temporal-lobe epilepsy  Most common type of epilepsy in adults.  In most, the seizure focus originates in the mesial temporal lobe.  The most common pathology in surgically resected specimens is that of mesial temporal sclerosis, gliosis and scarring in the mesial temporal lobe.  Complex partial seizures (CPSs) often begin with an aura, followed by decreased responsiveness, a motionless stare, and decreased awareness of oneself and the environment. o The aura is often emotional, olfactory or gustatory.  During a CPS, the patient may appear awake, with no loss of muscle tone, convulsions, tongue biting or urinary incontinence.