East Kent Locally Enhanced Service for Epilepsy

2. Overview of Epileptic Syndromes Focal Seizures 60% 0f Epilepsy Focal Cortical Disturbance Their origin usually determines the clinical picture Focal Spikes on eeg Primary Generalised Seizures Origin unclear either sleep spindles or hypersynchrony Commence bilaterally Spike and wave No aura

3. Focal vs. Primary Generalised Ep. Focal Epilepsy Aura Simple Sz.�s Complex Partial Sz�s Secondary Generalised Sz.�s P.G.E. Myoclonic Jerks Absence Atonic Sz�s Tonic Sz�s Tonic-clonic Sz.�s

5. Example of Primary Generalised Epilepsy Childhood absence seizure

6. Introduction to Epilepsy

7. Examples of Focal Seizures Focal motor seizure that becomes secondarily generalised. Likely focus in right frontal lobe

8. Treatment of newly diagnosed epilepsy When do you commence treatment? Has a diagnosis been reached? Which anti-epileptic medication? [NB female issues] Involve the person with epilepsy in the decision making

9. Cellular Electrophysiology Membrane Potential The Na+ / K+ Pump

10. Cellular Electrophysiology Selectively Permeable Membrane - Channels Depolarising Shift Epileptic Focus

13. Overview of established  Anti Epileptic Drugs Carbamazepine Partial Epilepsy � Not for Absence or Myoclonic Jerks Start at 100-200mg a day increase slowly S/E- diplopia, nausea, headache, dizziness Idiosyncratic reactions possible [up to 10%] Monitoring needed- increase �Chrono� dose Beware of interactions

14. Overview of established  Anti Epileptic Drugs Clobazam Used intermittently Extra cover for catamenial seizures, stressfull events , clusters of attacks Dose- 10mg [SLS] once or twice a day for 3 days

15. Overview of established  Anti Epileptic Drugs Clonazepam Limited role due to tolerance, sedation and withdrawal seizures Usually reserved for refractory seizures especially Myoclonic jerks

16. Overview of established  Anti Epileptic Drugs Ethosuximide Indication � Absence seizures [hence paediatric field usually] Introduce slowly 500mg daily increasing to 1-2 g a day Side Effects � GI and CNS

17. Overview of established  Anti Epileptic Drugs Gabapentin Add on therapy for partial seizures only Dose starts at 300mg a day and increases to 1800-2400 mg a day with t.d.s dosing No interactions[ not metabolised] Side effects � well tolerated occas. drowsiness, dizziness, diploplia, ataxia and headaches ? Efficacy

18. Overview of established  Anti Epileptic Drugs Lamotrigine Broad spectrum and first line [ less teratogenic than VPA] Dosing � slow to minimise side effects usually 25mg a day increasing every 2 weeks, b.d. dosing. Max dose around 400mg a day. Interactions � VPA , CBZ and PHT Idiosyncratic reactions in up to 5%

19. Overview of established  Anti Epileptic Drugs Piracetam Need a wheelbarrow ! Indications � refractory myoclonus Dose � 7.2g in t.d.s. dosage, increasing weekly to 12-24 g/day!! No known interactions

20. Overview of established  Anti Epileptic Drugs Phenytoin Was considered first line for partial seizures Poor side effect profile- rash , liver toxicity. blood dyscrasias, cosmetic changes, neurotoxicity etc Dosing difficulties � saturation kinetics Many interactions

21. Overview of established  Anti Epileptic Drugs Phenobarbitone [and Mysoline] World-wide best seller for partial seizures Side �effects largely unacceptable- effects on cognition, mood and behaviour. Also arthritic changes, dupytrons contracture, frozen shoulder Interactions- accelerates metabolism of many lipid soluble drugs

22. Overview of established  Anti Epileptic Drugs Sodium Valproate Broad Spectrum and Powerful [ no-longer first line in women] Dose � 300- 500mg a day, usually bd dosage Side effects- tremor, wt. gain, POS, possible hepatotoxicity, blood dyscrasias and pancreatitus Interactions- can inhibit liver enzymes

23. Overview of established  Anti Epileptic Drugs Vigabatrin Tertiary Care Initiation Peripheral field loss [permanent in up to 40%] Used for very resistant cases or in infantile spasms

24. Overview of the Newer  Anti Epileptic Drugs Topiramate Second line � Broad Spectrum [5 mechanisms of action] Dose starts at 25mg a day -2 in 3 tolerate it slowly increased to 200-400mg a day Side effects- Irritability, drowsiness, headaches, dizziness, cognitive slowing, speech impairment, weight loss and paraesthesia. Beware of kidney stones [occurs in 4 %]

25. Overview of the Newer  Anti Epileptic Drugs Tiagabine [ �safe� version of vigabatrin] Second line partial seizures only Dose- Started at 10 mg a day and can be increased to 30mg a day, t.d.s dosage Side-effects � sedation, headache, tiredness, dizziness, tremor, confusion. occas. can worsen seizures [status.] ? Efficacy

26. Overview of the Newer  Anti Epileptic Drugs Oxcarbazepine- analogue of CBZ Indications � same as CBZ, may worsen absence and myoclonic epilepsy. Dose � start at 300mg a day and increase to 900 � 2400mg a day as needed Side effects � hyponatraemia, headaches, occas. rashes and teratogenicity

27. Overview of the Newer  Anti Epileptic Drugs Levetiracetam � Piracetam derivative Licensed as second line for refractory partial epilepsy but is broad spectrum Dose- start at 125mg [half a tab] a day and build up to max of 3,000mg if needed Side effects � no known idiosyncratic reactions may cause somnolence, irritability [initially] Interactions � Nil definite ?? CBZ and PHT

29. Principles of Epidemiology Incidence Rate= new cases per year [n per 100,000 per year] For epilepsy is around 50 per 100,000 Point Prevalence = All cases with active epilepsy at a point in time [n per 1000]. For epilepsy is 4-6 per 1000 Active Epilepsy = to have had a seizure or treatment in the last 5 yrs

30. Epidemiology Prevalence is around 5-10 cases per 1000 [excluding Feb Sz. & Single Sz.] Lifetime Prevalence of single Sz. = 2-5% Incidence of Epilepsy is 50 cases per 100,000 per year Trough shaped curve for Incidence ie it peaks in childhood and later on in old age Regional Variations

31. Mortality in Epilepsy Up to 1000 deaths a year. 20% more men than women. No change in figures for over a decade SUDEP = 350-400 a yr in the UK Possible cardiac arrhythmias caused by channelopathies, bradycardia 2� to apnoea, endogenous opioids/endorphins. External obstruction likely to be a factor in up to 70% May effect up to 1 per 1000 with epilepsy 1 per 250 attending a tertiary epilepsy clinic If seizures are fully controlled, SMR falls to close to normal for the population Has been studied in small numbers � one was during video telemetry.

33. Principles of Neuro Imaging - CT Computed Axial Tomography CT scan = an image reconstruction Voxel � is a volume pixel and represents the depth of the slice Image is made from a grid consisting of the average density of each voxel within it Windowing � Only able to see a limited numbers of grey � select the area to attribute grey rather than black or white One CT is the equivalent to 24 months of background radiation

34. Principles of Imaging - MRI Certain atomic nuclei have an odd number of protons or neutrons e.g. hydrogen and phosphorous. This gives them the predisposition of �spin and magnetic movement,� [wobbly] Each has a resonant frequency. This resonant frequency is determined by exciting them with radio waves � turn it off and they re-emit radio waves The frequency and intensity of the radio waves reveals information about their environment. MRI � achieved by precise control of rapid magnetic field strength and radiofrequency pulses in combination to produce sequences

35. MRI Magnetic Resonance Imaging � Is achieved by the precise control of a combination of rapid magnetic field strength changes and radio frequency pulses. Together they form �sequences� Potential Hazards � No magnetic material must be present in the subject being imaged The radiofrequency must not be set too high a strength or else the subject will be �microwaved!�

36. Principle of MRI Image can be adjusted by altering sequences e.g. T1 weighted scan � water black T2 weighted scan water appears white Flair sequencing takes away CSF from T2 image Slices presented as if looking from below i.e. right = left Contrast medium �same as for angiography tend to use Gandolinium in T1 sequences

37. SPECT Scanning Single photon emission tomography Bolus of pure gamma emitter injected into patient bound to suitable carrier molecule- e.g. 99Tc 131I 68Ga. Carrier molecule should selected which is known to be concentrated in the specified organ or disease site SPECT- uses many camera angles then resulting projections used tomographically to reconstruct a slice Isotope injected during seizure and compared with inter ictal image.

38. PET Scan Proton Emission Tomography Injected isotope is emitter of positive electrons [ positrons] e.g. 15O. Has to be produced locally in cyclotron � hence expensive ++. The positron collides with neighbouring electron to produce positron annihilation. This results in the production of two gamma rays. These travel away from each other in opposite directions.

39. PET Scan Picked up by detectors and no need for energy inefficient collimators. Image can be produced by computing coincidence of the various lines of site detected Technique can be used to produce images reflecting glucose metabolism, blood flow and oxygen consumption

40. Functional MRI [fMRI] BOLD - Blood Oxygen Level Dependant Oxy-haemoglobin in non magnetic Deoxy-haemoglobin is magnetic Neuronal activity requires extra energy and cerebral blood flow increases locally hence the oxy/deoxy ratio increases Locally magnetic field becomes more uniform, signal increases a little Differences detected and visually represented

42. Special topics in the Management of Epilepsy, 1. Woman and Epilepsy Pregnancy and epilepsy. Pre-conceptual Care- ensure pregnancies are planned [high dose oestrogen pills if necessary, 4 packs of COC consecutively with 4 day pill free interval, Depo-provera every 10 weeks not 12.] Discuss modification of AED to reduce number and total dose Advise oral folic acid 5mg daily when intending pregnancy Belfast Register �.www.epilepsyandpregnancy.co.uk

43. Special Topics in the Management of Epilepsy Ante-Natal Care Continue 5mg Folic acid until at least 12 weeks Adjust AED if necessary on medical grounds Monitoring of plasma levels is not usually necessary [SIGN guidelines] Offer serum screening at 16weeks and anomaly scan at 18-22 weeks Prescribe oral vit K 20mg a day from 36weeks in on enzyme inducing AED Prolonged seizures can be controlled by IV Diazepam [ rectally is OK if IV access not possible] Belfast Register �.www.epilepsyandpregnancy.co.uk

44. Special Topics in the Management of Epilepsy Intra-Partum Care Continue usual AED regime during labour Control seizures with i.v. diazepam Early decision for LSCS if seizures uncontrolled Offer same range of analgesics as available to other mothers Give infant vitamin K 1mg IM at birth

45. Special Topics in the Management of Epilepsy Post Partum Care Encourage breast feeding Offer advice for safe settings for feeding, bathing etc. Review AED and contraceptive regimens Encourage pre-conceptive care for future pregnancies

46. Special topics in the Management of Epilepsy Catamenial seizures- �the clustering of epileptic seizures in relation to the menstrual cycle� Seizure control is worse in anovulatory cycles Oestrogen- inhibits GABA, potentiates glutaminergic transmission, increases neuronal metabolism and discharge rates and promotes kindling. Progesterone- its metabolites are barbiturate like ligands at GABA receptor, reduces neuronal transmission and discharge rate, suppresses kindling and inhibits epileptic discharges Seizures likely when oestrogen/progesterone ratio is highest

48. Sexual dysfunction in epilepsy Hypo sexuality � surveys suggest 22-67% reduction in sexual interest Erectile Dysfunction � occurs in 57%[ Toone et al 1989], up to 83% in TLE Sexual Functioning in Males [1989] Previous SI 56% [compared to 98% controls] S.I. in the previous month 43% [compared to 91% in controls] Previous erectile dysfunction 57% [compared to 18% controls]

49. Sexual dysfunction in epilepsy Approximately one third of women with epilepsy have anovulatory cycles POS associated with VPA treatment � some studies suggest up to 64% of women on VPA compared to 19% of controls. It may be linked to obesity with 2� hyper- insulinism causing increased ovarian androgen synthesis and structural changes in ovaries

50. Sexual dysfunction in epilepsy Psychiatric Depression � Up to 2/3 of PWE are depressed, with 2� reduced libido and effects of antidepressants Anxiety � self medicate with alcohol Psychosocial In one study [1988] of 92 patients with poorly controlled epilepsy 68% Had no friends 34% Never had a �true� friendship 57% Never had a steady relationship

51. Marriage Marriage rates for PWE Men > Women > general population Less likely to marry if seizures started before 10yrs in women and before 20yrs in men However if seizures well controlled by 12yrs marriage rate the same as general pop. Sexuality � often lowered by AED and hyposexuality reported in 50% of PWE involving the temporal lobe

52. Epilepsy and the family Most studies show marriage rates for PWE; Males > females less or equal general population Less likely to marry if seizure onset before 10yr Separation and Divorce Men with poorly controlled seizures since childhood have high rates of separation or divorce [? linked to deception and hiding of sz. And infidelity relating to sexual problems]

53. Social Aspects of Epilepsy Occupational � Unemployment, poor job-seeking skills, Non competitive, unskilled manual employment as a result of disadvantaged education, pressure of keeping current job Social � Social isolation as a result of no driving licence, unable to drink alcohol, stigma Tiredness Over protective parents

54. Employment Disability Discrimination Act 1995 & 1996Disability is defined as; �a physical or mental impairment which has a substantial and long term adverse effect upon one�s ability to carry out normal day to day activities.� Substantial is more than minor and long term is longer than 12 months Exclusions; Hay fever, tendency to set fires or steal, physical or sexual abuses of others Disability Discrimination Help Line Tel: 0345 622644

55. Employment Scope of problem 25-40% of employable PWE report having problems finding a job Statutory barriers to employment in PWE; Difficulties for Aircraft pilot, ambulance driver, armed services, RAF, coastguard, Diver, Fire Brigade, HGV and Taxi drivers, Merchant seaman, Nurse and midwife, Police, Prison service, even a Teacher in state school must be 3 yrs seizure free NB Loss of driving licence for some may mean loss of job.

56. Driving Collapse at the wheel- CVA 8% Heart 9% Diabetes 17% Blackout 22% Epilepsy 38% Others 7% Group1 Driving Licence- Must be 1 yr seizure free with a medical review before restarting or only nocturnal seizures for 3 yrs Group 2- Withdrawn for 10 yrs and can be re-issued if 10yrs seizure freedom and has not taken AD during the time or does not have a continuing liability to epileptic seizures

57. Driving AED Withdrawal Risk of developing seizure increases by 40% so advise patients not to drive during withdrawal and for 6 months afterwards Confidentiality If patients continues to drive inform patient not to If continues to drive advise if continues will inform DVLA [copy of warning letter to patient and GP] If still continues advise will inform DVLA and do so [occurs very exceptionally]