Contemporary Developments in Childhood Epilepsy Management. Olivia O Mahony, Cork University Hospital, Cork, and Mercy University Hospital
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1 Contemporary Developments in Childhood Epilepsy Management Olivia O Mahony, Cork University Hospital, Cork, and Mercy University Hospital
2 Developments in Epilepsy Care Standardised epilepsy care using evidence based diagnosis, investigation and management NICE guidelines Recent publications Irish National Model of Care BPNA PET program Prescribing advise Valproate Carbamazepine Diagnostic difficulties Evolving syndromes (Dravet s Syndrome) ILAE Epilepsy Classification
3 Aims Accurate diagnosis As well controlled epilepsy as possible Free of side effects Well managed co-morbidities Good quality of life for the child and family Reaching maximal developmental potential Well adjusted adult
4 Lecture Breakdown Definition and Statistics Diagnosis Investigations Treatment Special Syndromes
5 Definition and Statistics
6 Definitions An epileptic seizure is an intermittent, stereotyped disturbance of behaviour, emotion, motor function or sensation resulting from abnormal cortical neuronal discharges Epilepsy is the tendency to have recurrent epileptic seizures
7 Epilepsy Summary 1 in 200 children have epilepsy Incidence much higher in the first year of life 1 in 3 children with CP have epilepsy 1 in 3 children with hydrocephalous have epilepsy 30% of children and adults with autism have epilepsy 80% with Sturge Weber and TS and 3% with NF1 have epilepsy Febrile seizures 4%
8 Co-morbidities High incidence of learning difficulties, autism, neurocutaneous disorders 35-56% attending paediatric neurology clinics have significant behavioural problems Anti social behaviour X 2.3 ODB X4 30% may have ADHD inattentive type High risk Additional neurologic impairment Significant cognitive delay Poorly controlled seizures Quality of Life Data poorer for epilepsy than other chronic conditions
9 Stats 5% of individuals will have a seizure with a risk of recurrence of 30% max in the first 6 months Likelihood of seizure freedom with treatment 60-70% 30-40% refractory to drug treatment With failure to have any response to the first drug only 11% become seizure free with subsequent drugs but the chance is never 0% Failure to respond to 3 appropriate AEDS <5% chance of seizure freedom Treatment options Anti epileptic medication Dietary Low glycaemic index diet Modified ketogenic diet Ketogenic diet Surgery Resective VNS
10 Stats 2 Growing out of epilepsy 70% outgrow by 20 years Single seizure type 2-5 years seizure free Normal neurological exam & imaging Risk of recurrence Highest while weaning and first 6 months off Low risk of recurrence if 2 years seizure free off meds Risk of intractability with recurrence 1%
11 SUDEP Risk of SUDEP 0.35/1000 person years Postictal respiratory insufficiency Cardiac arrhythmia induced by a seizure Reduce risk ID cardiac arrhythmias as a cause of misdiagnosed epilepsy Control seizures as well as possible Beware nocturnal seizures Overall risk of premature death is 2-3 times greater than the normal population but much of this risk is related to the underlying cause of epilepsy eg brain tumour, neurodegenerative disorders
12 Diagnosis
13 Diagnostic Difficulties Children are prone to non epileptic paroxysmal events causing diagnostic confusion Every epileptic seizure type has a non epileptic differential 30% of individuals referred to a specialist clinic did not have epilepsy Concordance among neurologists for epileptic events is high but there is a tendency to overcall as epileptic non epileptic events
14 Getting it right Describe the event Trigger Onset and progression through event Duration Recovery time Touch/move child during events of uncertain cause Record events
15 Investigations
16 EEG Strongly predictive of epilepsy % population have epileptiform discharges 5% of children 1 st EEG positive in 56% 2 nd in 26% Sleep increases the yield 10-15% The EEG should not be used in isolation to make a diagnosis of epilepsy An EEG may be used to help determine seizure type and epilepsy syndrome where epilepsy is suspected. This enables correct prognosis. Inappropriate EEG use Day-dreaming or bad behaviour in patients with autism (unless neurologist suspects independent seizures) Funny turns when clear history of breath holding/tics/vasovagal events. It is actually contraindicated in these cases (false positive findings) Prolonged visual or auditory hallucinations in psychiatric patients other than the well described elemental hallucinations of parietal/temporal lobe epilepsy
17 Neuroimaging Neuroimaging should be used to identify structural abnormalities that cause certain epilepsies. MRI should be the imaging investigation of choice. MRI is particularly important in those: who develop epilepsy before the age of 2 years or in adulthood who have any suggestion of a focal onset on history, examination or EEG (unless clear evidence of benign focal epilepsy) in whom seizures continue in spite of first-line medication. In an acute situation, CT may be used to determine whether a seizure has been caused by an acute neurological lesion or illness.
18 Other tests In children and young people, other investigations, including blood and urine biochemistry, should be undertaken at the discretion of the specialist to exclude other diagnoses, and to determine an underlying cause of the epilepsy. A 12-lead ECG should be performed in individuals with suspected epilepsy. In cases of diagnostic uncertainty, a referral to a cardiologist should be considered. Use of home video recording with instruction
19 Treatment
20 When is seizure treatment needed? Single prolonged seizure i.e.>5min Most sz<5min, lasting >5min at risk of SE Early treatment more likely to be successful Clusters of seizures 3 or more sz per hour Risk of recurrence is high Acute symptomatic seizures Is it epilepsy (2 or more unprovoked seizures)- long-term treatment
21 Outcome of Status Epilepticus Mortality 3.6-7% Refractory 16% Death primarily in acute symptomatic SE (infants) or progressive encephalopathy Morbidity 9-28% Low with febrile or idiopathic SE High risk of ICU admissions with over use of benzodiazepines ideally 2 doses of benzodiazepines and then proceed to second line medication
22 Rescue medication indications (prescribing and administering) for patients in the community (message to GPs, schools etc.) Always remember it is an EMERGENCY medication It is not for shortening prolonged complex partial seizures which have a minimal motor or respiratory component. Prolonged generalised tonic clonic seizure (GTCS) more than 5 minutes (Emergency) Tonic seizures with cyanosis or prolonged more than 5 minutes (Emergency) Known patients who usually have rare or infrequent seizures, if they cluster frequently over a short period on one day and/or are known to progress to habitually prolonged GTCS when they cluster (preventing a very likely emergency) If a patient required emergency medication in the past and is weaning off their antiepileptic medications they should have rescue medication for a further 2 years. Patients who live in remote areas with a known prolonged emergency/ambulance response time and who are known to have generalised tonic clonic seizures, primary or secondary generalised. Patients in remote areas with prolonged emergency/ambulance response time could be allowed a second dose of rescue medication if first dose has not terminated the seizures within minutes of administration provided that it is continuing with no signs of slowing down or fading and provided that ambulance is called. This is particularly relevant and justified if it has been used before in such settings (twice within 24 hours) and known to have been tolerated with no respiratory depression.
23 First-line treatment in children, young people and adults with newly diagnosed focal seizures Offer carbamazepine or lamotrigine as first-line treatment to children, young people and adults with newly diagnosed focal seizures. Likelihood of an allergic rash- carbamazepine (HLA- A*3101) Marker for Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (30% mortality) in Han Chinese FDA recommends HLA testing before using carbamazepine in patients of Asian descent
24 First-line treatment in children, young people and adults with newly diagnosed GTC seizures Offer sodium valproate as first-line treatment to children, young people and adults with newly diagnosed GTC seizures. Be aware of the teratogenic and developmental risks of sodium valproate Offer lamotrigine if sodium valproate is unsuitable. If the person has myoclonic seizures or is suspected of having juvenile myoclonic epilepsy (JME), be aware that lamotrigine may exacerbate myoclonic seizures.
25 Valproate in Pregnancy In women who take valproate while pregnant, around 1 in 10 babies will have a birth defect. Birth defects seen when mothers take valproate during pregnancy include: spina bifida facial and skull malformations malformations of the limbs, heart, kidney, urinary tract and sexual organs. In women who take valproate while pregnant, about 3 4 children in every 10 may have developmental problems. The long-term effects are not known. The effects on development can include: being late in learning to walk and talk lower intelligence than other children of the same age poor speech and language skills memory problems. Children exposed to valproate in the womb are more likely to have autism or autistic spectrum disorders. There is also some evidence children may be more likely to be at risk of ADHD.
26 Current Advise Valproate should not be used in female children, in female adolescents, in women of childbearing potential and in pregnant women unless other treatments are ineffective or not tolerated. Women of childbearing potential must use effective contraception during treatment. No-one should stop taking valproate without discussing it first with their doctor and the benefits of valproate treatment must be carefully balanced against the risks. If valproate is the only option, women of childbearing age should be given effective contraception. Women taking valproate must have regular reviews of their treatment.
27 Ongoing monitoring Maintain a high level of vigilance for treatment-emergent adverse effects AED levels should not be routinely monitored but can be helpful for detection of non-adherence to the prescribed medication suspected toxicity adjustment of phenytoin dose management of pharmacokinetic interactions (for example, changes in bioavailability, changes in elimination, and co-medication with interacting drugs) specific clinical conditions, for example, status epilepticus, organ failure and certain situations in pregnancy Examples of useful blood tests include: before surgery clotting studies in those on sodium valproate full blood count, electrolytes, liver enzymes, vitamin D levels, and other tests of bone metabolism (for example, serum calcium and alkaline phosphatase) every 2 5 years for adults taking enzyme-inducing drugs. (Phenobarbitone, carbamazepine, phenytoin) Asymptomatic minor abnormalities in test results are not necessarily an indication for changes in medication.
28 New treatments Cannabis oil Experimental treatment No standard product THC CBD Very variable results to date Better (some dramatic Dravets syndrome) No change Worse Interactions with other AEDs Long term side effects unknown Controlled substance- importation issues
29 Special considerations
30 Dravet s Syndrome Dravet's Syndrome is a genetic epilepsy from an SCN1A mutation accounting for at least 7% of severe epilepsies beginning in the first 3 yrs.' of life. It is a clinical and genetic diagnosis. The mutation often occurs De Novo but there may be a family history of febrile seizures. Focal or generalised seizures beginning in the first 12 months of life often related to fever or vaccination Seizures begin as febrile, but later also appear without a fever Episodes of status epilepticus Myoclonic and absence seizures occur around the age 18 months of age Seizures intractable despite medication Initial development is normal, then slows or stagnates in the second year of life Variable EEG with early onset photosensitivity Gait deterioration in adolescence 15% mortality by adult life
31 Treatment Anticonvulsants frequently used in treatment: clobazam /clonazepam levetiracetam stiripentol topiramate /zonisamide valproic acid Medications that can worsen seizures Carbamazepine, phenytoin,lamotrigine, oxcarbazepine, vigabatrin All patients need an individualised acute seizure plan and a status epilepticus protocol Multidisciplinary team review
32 SCN1A mutation Phenotypes No seizures Migrating Partial Seizures of Infancy Rarely infantile spasms Dravet s Syndrome Febrile seizures Febrile seizures plus
33 Finally
34 Quality of Care Measures of Quality Epilepsy related morbidity and mortality SUDEP, Status Epileptics Morbidities related to the disease and the treatments Injuries Proportion of patients seizure free Admission/length of stay/readmission Rational use of resources EEG Neuroimaging Treatments
35 Aims Accurate diagnosis As well controlled epilepsy as possible Free of side effects Well managed co-morbidities Good quality of life for the child and family Reaching maximal developmental potential Well adjusted adult
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