Epilepsy Flashcards

Question

what are the challenges associated while choosing an epilepsy medication?

Answer 1

- several comparison studies: minimal differences in efficacy of standard AEDs - thus, differences in profile of expected adverse effect, pharmacokinetic and cost should guide AED choice - most patients can be optimally managed w single AED therefore, one mist be sure that drug oven has failed before moving on to alternative drug or two drug combination - if patient has persistent seizures but no adverse effects from the drug then the dose can be increased as tolerated or until seizure control in obtained - the “therapeutic range” of serum concentrations given is only a guideline—the patient’s clinical state determines the appropriate dose

Answer 2

1. epilepsy medication | 2. epilepsy surgery

Answer 3

Marson et al. - an unblinded RCT, THE SANAD studied the effectiveness valproate, lamotrigine or topiramate for generalised and unclassifiable epilepsy and found valproate. was effective. for focal but. not generalised

Answer 4

1. partial - focal 2. simple partial - focal w/o impaired awareness 3. complex partial - focal w impaired awareness 4. secondary generalised TCS - focal evolving to bilateral convulsive seizure 5. cryptogenic - unknown 6. symptomatic - metabolic/structural 7. idiopathic - genetic

Answer 5

Age - normal EEG of a child is very different from adult Artefacts - chewing Conscious Level - sharp waves seen in cortex while sleeping Drugs - burst depression seen under anaethesia Cerebral Pathology - cerebral palsy shows abnormal EEG but not necessarily seizures

Answer 6

1. photo stimulation 2. hyperventilation: vasoconstriction provokes seizure 3. sleep and sleep deprivation 4. long term monitoring: ambulatory and video-telemetry

Answer 7

1. wake EEG - 50% 2. Sleep EEG- 80% 3. repeat wake and sleep EEG - 92%

Answer 8

EEG epileptiform in 0.5 – 4 % healthy adults however the population is not healthy

Answer 9

1. Diagnosis (ictal) - epilepsy vs non-epilepsy - interictal period reflecting epileptiform activity consists of bursts of abnormal discharges containing spikes or sharp waves - epileptiform activity not specific for epilepsy but has a greater prevalence in epileptic population than others - however, even in an epileptic patient, the initial interictal EEG may be normal up to 60% - thus, EEG cannot establish the diagnosis of epilepsy in many cases 2. Classification (ictal/ interictal) - general or focal - however, absence of EEG seizure activity does not exclude seizure disorder as focal seizures may originate from a region in cortex that cannot be detected by standard scalp electrodes - since seizures typically infrequent and unpredictable often difficult to obtain EEG during a clinical event - thus, video EEG telemetry unit for hospitalised patients or use portable equipment to record EEG continuously on cassettes >24h in ambulatory patients - video approach now a routine approach for accurate diagnosis of epilepsy in patients w poorly characterised events or seizures that are difficult to control 3. Classifying seizure disorders and aid in the selection of anticonvulsant medications e.g. - episodic generalised spike-wave activity seen for absence (3Hz) as well as epilepsy syndromes like JME + LGS - west syndrome: Hypsarrhythmia EEG - focal interictal epileptiform discharge seen in TLE and frontal lobe discharges a. frontal: limb jerking, headache or eye deviation b. parietal: sensory disturbance - spreading tingling c. temporal: deja vu, jamais vu, memories, feeling dread, rising feeling d. occipital - positive visual disturbance - coloured balls 4. monitor the progress - normal EEG -> better prognosis - abnormal background or profuse epileptiform activity -> poor - however, this is also a limitation of EEG in epilepsy 5. Work-Up for Epilepsy Surgery (ictal/ interictal)- concordance w MRI abnormality 6. Management of Status Epilepticus - convulsive or non-convulsive ??

Answer 10

1. monitoring of progress - not imp. if EEG changes or not after treatment but imp how patients reposed to the treatment 2. anti-convulsant withdrawal in adults - anti-convulsants have better results in children 3. diagnosis in the presence of intracerebral disease 4. diagnosis where history is of syncope - EEG should not be done of its a blackout 5. driving - the regulation change every few years of driving

Answer 11

1. Vagal nerve stimulation (VNS) 2. Deep brain stimulation (DBS) 3. Resective surgery 4. Ketogenic diet 5. Complementary therapies

Answer 12

- an adjunctive treatment for epilepsy with focal or generalised onset - it is used for refractory patients who seizures have not been controlled after trial 2/3 medications and are not suitable for resective surgery - Aims to reduce the frequency and/or intensity of seizure activity, shorten recovery time and lessen side effects

Answer 13

- a pulse generator is impacted into a pocket of skin normally not he left - wires and electrodes travel under the skin and are connected to the left vagus nerve in the neck - The stimulator is programmed to send regular, mild electrical impulses to the vagus nerve and can also be controlled by use of a magnet. The newest VNS model is also sensitive to a rise in HR (Eggleston et all, 2014).

Answer 14

- aims to reduce seizure activity by up to 60% interrupting and preventing the electrical irregularities on the surface of the brain, that cause seizures. - improved alertness and memory and fewer mood problems. - Therapy is reported to improve over time, side effects lessen over time - proffered by patients over brain surgery

Answer 15

- Not possible to know in advance who will have seizure reduction and to what extent - Can take up to 2yrs to achieve optimum seizure control - Mild side effects: laryngeal nerve travels within the mid cervical region of the left vagus nerve also so hoarseness of voice occurs each time the device activates + coughing - Battery changes every 6-8- years

Answer 16

- hypothesis - CN10 afferents - numerous projects in CNS - so AP generated in vagal afferents have potential to affect the entire organism however, the precise MOA and how it suppresses seizures remains to be elucidated - aim: to induce AP within different types of fibres that constitute the nerve at the cervical level. however, the fibres responsible and/or necessary for its seizure suppressing effect are unknown - unidirectional stimulation activating afferent vagal fibres, is preferred, as epilepsy is considered a disease with cortical origin, and efferent stimulation may cause adverse side effects.

Answer 17

- LivaNova developed VNS - reported that 2 year therapy 64% of patient has more than a 50% reduction in the frequency of their seizures. - There are patients that have become seizure free with VNS but that’s not what they vouch it can do - studies by LivaNova have shown that 82% of patients have inter-ictal tachycardia and so the device is sensitive to this rise and sends an additional boost of electrical stimulation to the nerve in an attempt to abort or shorten the seizure - Live Nova state that it can take up to 2 years to see the full impact of the VNS. - Side effects can re-emerge when we increase settings but usually settle after 24-48 hours, such as a cough upon stimulation. - after the initial surgery patients need to come back to see us every 2 weeks to build up the level of stimulation to a therapeutic level and then every 3-6 months depending on response to therapy/seizure control/battery life. - Licenced in states to treat depression but it improves mood

Answer 18

- has an influence on the production of serotonin, (this has been proven via cerebral spinal fluid (CSF) samples) - VNS has de-syncronization function on the EEG rhythms and VNS has influence on the cerebral Blood flow (CBF) to both the thalamus and the cortex - All this together, has an anti-epileptic effect.

Answer 19

- an adjunctive treatment for epilepsy with focal onset - used for refractory patients who seizures have not been controlled after trial 2/3 medications and are not suitable for resective surgery - Aims to control excess electrical activity in the brain using regular electrical impulses to reduce the frequency and severity of seizures - involves implanting electrodes into specific areas in the brain

Answer 20

- thin wire implanted into the brain - wire is attached to an electrical stimulator placed under the skin - surgery takes few hours, 3-5 hrs hospital stay, switched on 2-4 wks after

Answer 21

- risks - haemorrhage (1-2%) and infection (3-5%) - following surgery, memory problems and depression may reduce over time - trials show seizures become less frequent in some people - in others, it may reduce the seizures a little or have no effect

Answer 22

- same as VNS - not widely available in the UK currently, still a relatively new treatment in field of epilepsy care and not currently available in shef - evidence on efficacy of DBS for refractory epilepsy is limited in both quantity and quality - evidence on safety shows serious but well-known side effects - therefore, this procedure should only be used w special arrangements for clinical governance, consent and audit or research according to nice guideline jan 2012

Answer 23

- suitable for focal seizures - if several AEDs trialled and none of them have stopped or reduced the seizure frequency by half - a physical cause for epilepsy such as scarring on brain or head injury or an infection like meningitis and this can be identified on scan and is only in one area of brain

Answer 24

- aim to dramatically reduce or stop the occurrence of seizures - around 70% of people become seizure-free - after surgery most people will still take their AEDs for 2 yrs

Answer 25

- brain surgery so carries significant risks, i.e. death, stroke, paralysis, worsening of epilepsy - approx 50% of patients recommended for surgery are unable to proceed after formal testing - 2yr work up - investigations: MRI, EEG plus telemetry, PET, SPECT neuro-psychotherapy and psychiatry

Answer 26

- special high-fat, low-carbohydrate diet - one treatment option manly for children w epilepsy whose seizures are not controlled w AEDs - particularly recommended for children w Lennox-gastaut syndrome but useful in any seizure type - now available in adult service

Answer 27

- patients are first seen by neurologist and if suitable will be offered a low glycemic diet - if this works they can remains on this - if it does not work they are passed onto a specialist dietician for guidance on ketogenic diet

Answer 28

- may help to reduce the number or severity of seizures - can often have positive effects on behaviour - research also shows that it has an anti-epileptogenic effect on the brain

Answer 29

- ketones are formed when the body uses fat as its source of energy - the body usually carbohydrates (such as break, sugar, pasta) for its but because ketogenic diet is low in carbs, fats become the primary source of energy instead - when the body is in ketosis, the ketones can cross the BBB and cause an anti-epileptic effect - ketones are one of the more likely mechanisms of action of the diet; with higher ketone levels often leading to improved seizure control

Answer 30

- If seizures have been well controlled for some time, usually 2 years, the doctor might suggest going off the diet - Usually, the patient is gradually taken off the diet over several months or even longer. Seizures may worsen if the ketogenic diet is stopped all at once - Children usually continue to take seizure medicines after they go off the diet - In many situations, the diet has led to significant, but not total, seizure control. Families may choose to remain on the ketogenic diet for many years in these situations

Answer 31

1. Kidney stones 2. High cholesterol levels in the blood 3. Dehydration 4. Constipation 5. Slowed growth or weight gain 6. Bone fractures

Answer 32

1. Co-morbid depression/anxiety – those with refractory epilepsy at high risk 2. Low self-esteem 3. Psycho-social problems: Education, Employment, Relationships. Social isolation 4. Psychosis 5. Self harm 6. Anger, frustration & violence 7. Adjustment/acceptance issues 8. Suicidal thoughts, attempts and actual suicide 9. Sleep disturbance

Answer 33

True, the main ones are - major depressive disorder, anxiety disorder, mood/anxiety disorder, suicidal ideation

Answer 34

1. Learning and educational problems 2. Personality and behaviour difficulties 3. Psychiatric disorders 4. Cognitive slowing and memory problems

Answer 35

- relaxation, CBT, biofeedback - may be used in conjunction w AED therapy in adults where other the person or specialist considers seizure control to be inadequate w optimal AED therapy - this may be associated with an improved quality of life in some people (NICE,2012)

Answer 36

1. Aromatherapy – with caution 2. Meditation – repeated can alter EEG patterns + or – effect on seizures 3. Herbal remedies - CBD oil, studies in over 3000 people have shown 1 in every 8 will have a 50% reduction in seizures

Answer 37

- Rochester et al. (2011), a population based study found that the cumulative incidence and life time risk of epilepsy increases with advancing age, this is crucial because: 1. One in 26 people will develop epilepsy in their life time 2. The lifetime risk provides an estimate of an individual’s risk for epilepsy over his or her remaining lifetime and assist heath care planners as they estimate service needs for epilepsy - at the age 20, there is RLR (relative lifetime risk) of 0.2 (2 in 1000)

Answer 38

- younger age (infants): skull is thin - highest risk of TBI, usually non-accidental perhaps birth trauma - middle age (teenagers): skulls gets steadier but irresponsible teens, especially men as they're more prone to injuries - older age (elderly): have higher rates of falling therefore, high risk of TBI, men=women

Answer 39

``` 1. LOC mild TBI - less than 30 mins moderate TBI - more than 30 mins and less than 24 hours severe TBI - more than 24 hours 2. Skull fracture mild TBI - absent moderate - could be present or absent severe TBI - contusion, hematite or skull fracture 3. PTA (post traumatic amnesia) mild TBI - less than 1 day moderate TBI - more than 1 day and less than 7 days severe TBI - more than 7 days ```

Answer 40

different definitions for different TBIs, not standardised

Answer 41

immediate seizure - within the first day of injury; occur in less than 24 hours after injury early seizure - within the first weeks of injury (acute symptomatic seizure) late seizure - after one week of injury (constitute the diagnosis of PTE)

Answer 42

Big sample sizes Huge variation in incidence of PTE Some retrospective and prospective

Answer 43

1. sex: male 2. history: alcohol abuse 3. clinical findings: PTA, focal neurological signs, LOC at initial TBI, 4. Abnormal neuro-imaging findings: skull fracture, midline shift, brain contusion, SDH, ICH 5. Clinical severity of TBI: MBI, SBI and acute symptomatic seizure

Answer 44

1. Huge sample size, prospective study - Risk of developing epilepsy is still higher after 20-30 years later Mild, moderate and severe - Severe brain injury carries a relatively higher risk of PTE - Epilepsy is highest in the first few years, risk continues to decline or separate from the baseline risk after 20 yrs of the moderate and mild 2. 78000 population study in Denmark - High risk with severe brain injury and PTE - Shows relative risk rather than absolute proportion with epilepsy - RR is highest in the beginning and then falls but never falls down to the baseline

Answer 45

provides an opportunity to study the therapeutic potentials

Answer 46

- higher risk of epilepsy after PBI, increases by >50% - famous example: Phineas gage - injury in 1848 but started seizures in 1860 - after 12 years, died from status epileptics a few months later - the 12 years highflying the latent period

Answer 47

- a longitudinal study of 90 patients - studied the effect of two things on the development of PTE – acute symptomatic seizures (25%) and haemorrhagic temporal lobe epilepsy (75%) - Temporal lobe is a common site of onset of seizure - Half of them went for long term follow up – 45% developed PTE 38% seizures on cEEG (continuous EEG) - Together highlighting, temporal lobe injury and early seizures predict the development of PTE

Answer 48

- seizure that lasts >30 mins (most seizures <5m) - or multiple seizures w/o recovery - w impaired LOC in inter-octal period - traditionally, by definition SE: 15-30m - practically, SE in which duration prompts acute use of ant-convulsant therapy for e.g. GCSE >5m

Answer 49

1. generalised convulsive status epileptics (GCSE): rhythmic jerking, tonic-clonic movements, impaired mental status, 2. non-convulsive status epileptics

Answer 50

- cardiorespiratory dysfunction, hyperthermic, metabolic derangements develop as a consequence of prolonged seizures resulting in irreversible neuronal injury - CNS injury could occur when patient is paralysed w neuromuscular blockade but continues to have seizure

Answer 51

- anti-convulsant withdrawal or non-compliance - metabolic disturbances - drug toxicity - CNS infection - CNS tumours - refractory epilepsy - head trauma

Answer 52

- GCSE is prominent initially when the patient is having convulsions however, the signs become subtle with increasing time - later, the patients might have only mild clonic movements of fingers or fine fine rapid eye movements - episodes of tachycardia, hypertension, pupillary dilation could also be present - in such cases, EEG is the only method of establishing the diagnosis - patients stops having prominent seizure but remains comatose due to being paralysed w neuromuscular blockage (to protect the airway), an EEG is essential to rule out the on going SE

Answer 53

- Stage 1 (0-10m): ABCD, BGC levels - samples ent to lab to identify metabolic abnormalities - anti-convulsant therapy w/o delay

Answer 54

- inter-ictal EEG for focal seizures often normal or may show brief discharges called as epileptiform spikes or sharp waves - since focal seizures arise from mTL or inferior frontal lobe (regions distant from the scalp), the EEG recorded during the seizure may be non-localising - however, the seizure focus if often detected using sphenoidal or surgically placed intracranial electrodes

Answer 55

1. jacksonian march (secs): motor movements begin in a restricted region (fingers) and gradually progress to include larger portion of extremity 2. Todd's paralysis (min-hours): localised paresis 3. epilepsia partíais continua (hours-days) - rare, often refractory to medical therapy

Answer 56

- since the collateral witness tend to emphasise more on the dramatic generalised convulsive phase of the seizure and over look the more subtle focal symptoms present at onset - at times, focal onset is apparent only when a careful history identifies a preceding aura - distinguishing between the two is essential as there could be substantial differences in the evaluation and treatment b/w them

Answer 57

- EEG: hypsarrthymia consisting of diffuse, giant slow waves w chaotic background of irregular multifocal spikes and sharp waves - EEG background suppressed: electrode decremental response - EMG may help distinguish it from tonic and myoclonic seizures as it showed characteristic EMG pattern - occurs mainly in infants - could be due to neuronal function and connectivity in the developing CNS

Answer 58

- children - triad 1. multiple seizures: usually GTC, atonic and atypical absence 2. EEG: <3Hz slow spike and wave discharges 3. impaired cognitive function but not in all cases - associated w CNS disease or dysfunction like developmental abnormalities, perinatal hypoxia/ischemia, trauma, infection, acquired lesions - poor prognosis due to underlying diseases and consequences of sever poorly controlled epilepsy

Answer 59

- changes in local structure ->

Answer 60

- identifies any underlying structural abnormalities - exception: children w absence seizures - MRI superior than CT for detecting cerebral lesion associated w epilepsy - incidental findings like tumours, vascular malformation that need immediate therapy - new MRI methods has increased the sensitivity in detected cortex abnormalities including hippocampal atrophy associated w mTLE - but for suspected CNs infection or mass lesion: CT should be performed when MRI is not available, also CT is quicker - PET, SPECT used for some patients w refractory seizures

Answer 61

- increase in seizure frequency around menses - either due to effects oestrogen + progesterone on neuronal excitability or changes in AED levels due to altered protein binding or metabolism - some may benefit from increase AED dosage during menses - natural projections or intramuscular medroxyprogesterone may benefit to some women

Answer 62

- most women w epilepsy who become pregnant will have an uncomplicated gestation and deliver a normal baby - however, there are some risks 1. seizure frequency = unchanged in 50% = increase in 20% = decrease in 30% - changes attributed to endocrine effects on CNS, variations in AED pharmacokinetics, changes in medical compliance - useful to see patients at frequent intervals during pregnancy to monitor serum AED levels 2. fetal abnormalities in children born = 5-6% epileptic mothers as compared to = 2-3% healthy mothers - higher incidence in epileptic mothers due to teratogenic effects of AEDs and the risk increase with number of medications used (10-20% risk of malformations w 3 drugs) and possibly w higher doses - recent meta analysis, common malformations?: cardiovascular and musculoskeletal system (1-2%) - VPA strongly associated w increased risk of adverse fatal outcomes (7-20%) - little known about the safety of newer drugs although reports suggest, higher than expected risk of cleft lip or palate w use of lamotrigine during pregnancy - advisable to have patients on mono-therapy w low doses - type and frequency of seizures may allow them to safely come off the AEDs prior to contraception - patients should take folate as the anti-folate effect of anticonvulsant are thought to play a role in neural tube defects, although this benefit remains to be proved - AED medication are excreted into breast milk to a variable degree - the ratio ranges from 5% (VPA) to 300% (levetriacetam) - however, provided the known benefits of breast feeding and the lack of evidence of long term to infants by exposed to AEDs, mothers can be encouraged to breast feed

Answer 63

- 2 main phase: initiation and propagation - initiation phase: 1. high frequency bouts of AP - extracellular Ca2+ influx -> long lasting depolarisation -> NGSC opening -> Na+ influx -> receptive AP -> followed by hyperpolsarisation mediated by GABA R or K+ channels (depending on cell type) 2. hypersynchronisation: the synchronous bursts from a sufficient number of neurones result in spike discharge on EEG - normally, spread of bursting activity prevented by intact hyperpolarisation and inhibition by inhibitory neurones - normal seizure circumstances

Answer 64

- UK: around 15,000 w NEAD excluding the misdiagnosis of epilepsy (NEAD society) - Epilepsy Foundation (US): - 20-30% seen an epileptic intractable seizures diagnosed w PNES - Prevalence rate in general population: 2-33 per 100,000 making PNES as prevalent as MS or trigeminal neuralgia

Answer 65

- misdiagnosis of epilepsy in people w PNES is very common - 25% of people previously diagnosed w epilepsy and are not responding to AEDs have been misdiagnosed - PNES difficult to diagnose cause: 1. pshyicians taught almost exclusively to consider physical disorders as the cause of physical symptoms 2. diagnosis of seizures mainly depends on the collateral witness who may not be trained to notice the subtle differences b/w seizures and non-epileptic seizures 3. many neurologists do not have access to video EEG

Answer 66

- attacks that resemble epileptic seizures but are not caused by abnormal brain electrical discharges - instead, are a manifestation of psychological distress - may look like they are experiencing GTC with falling and shaking. - less frequently, may mimic absence seizures or focal impaired awareness seizures - not a unique disorder but are a specific type of a larger group of psychiatric conditions that manifest as physical symptoms - used to be called somatoform disorders (DSM4) and are now termed somatic symptoms disorders (DSM5) - treatments: CBT, SSRIs - treatment issues: difficult to treat as when one symptom is extinguished, another symptom appears

Answer 67

- multifactorial, associated w abnormal emotional development in childhood - a specific traumatic event, such as physical or sexual abuse, incest, divorce, death of a loved one, or other great loss or sudden change, can be identified in some people with PNES - tend to develop during adolescence or early adulthood but may occur at any age, also appears to be more common in women - ICM: genetic predisposition -> NEAD vulnerable -> NEAD

Answer 68

- EEG: less specific even for epilepsy as diagnosed epileptic patients have normal EEG - therefore, video EEG used to monitor the patient for hours or days till a seizure occurs - analysis of video and EEG could provide a certain diagnosis of PNES - traditionally, video EEG performed at hospital but w modern equipment it can be permed at home also - when videoEEG. unavailable, cell phone videos obtained by collateral witness also helpful in suspecting PNES

Answer 69

``` 1. triggered by emotion NEAD - common epilepsy - rare 2. onset NEAD - gradual epilepsy - rapid 3. duration NEAD - prolonged epilepsy - secs-mins 4. cyanosis NEAD - rare epilepsy - common (GTC) 5. consciousness NEAD - may interact epilepsy - unconscious 6. movements NEAD - semi-purposeful (avoid harm), pelvic thrusting epilepsy - commonly limbs + GTC 7. eye opening NEAD - resist eye opening epilepsy - unable to resist 8. post-ictal symptoms NEAD - rare epilepsy - common 9. breathing NEAD - continuous epilepsy - periods pf apnoea ```

Answer 70

- normal seizures: glutamate induces excitatory bursts counteracted by inhibitory GABA release terminating the seizure - in SE, the seizure does not terminate leading to prolonged excitation due to glutamate 1. early stage (mins) - increased glutamate release - decreased GABA release + inactivation of GABAa receptors 2. middle stage - internalisation of GABAa receptors - increased AMPA receptor release onto the post-synapse - increased release of pro-convulsive peptides (glutamate) 3. late changes - abnormal gene expression - plastic changes w synapses increasing the risk of future seizures

Epilepsy Flashcards

(95 cards)