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Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana
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Alternative approaches to conventional anti epileptic drugs in management of pediatric Epilepsy - Dr Vijay Sardana

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  • 1. Alternative approaches to conventional antiepileptic drugs in the management of pediatric epilepsy Dr. Vijay Sardana MD,DM (Neurology) Head Department of Neurology Medical College, Kota
  • 2. Epilepsy- Pharmacological treatments <ul><li>1850s-Bromides </li></ul><ul><li>1912-Phenobarbital </li></ul><ul><li>Last 2 decades- Many AEDs </li></ul>
  • 3. <ul><li>Seizure control achieved in 75 % children with conventional AEDs </li></ul><ul><li>Increasing concern amongst parents about side effects </li></ul><ul><li>Non conventional methods may have role in intractable seizure/AED toxicity </li></ul>
  • 4. Non conventional methods <ul><li>Evidence base </li></ul><ul><ul><li>non randomized uncontrolled trials </li></ul></ul><ul><ul><li>Retrospective Studies </li></ul></ul><ul><li>Steroids in West Syndrome </li></ul><ul><li>Epilepsy Surgery </li></ul><ul><ul><li>Strong evidence </li></ul></ul>
  • 5. Non conventional antiepileptic drug (AED) treatment of Epilepsy <ul><li>Non-AED medical treatment </li></ul><ul><ul><li>Steroids (for example, ACTH [tetracosactide], prednisolone) </li></ul></ul><ul><ul><li>Intravenous immunoglobulins </li></ul></ul><ul><ul><li>Vitamins (for example, pyridoxine, pyridoxal phosphate, biotin, folinic acid) </li></ul></ul><ul><ul><li>Melatonin </li></ul></ul><ul><li>Dietary manipulation </li></ul><ul><ul><li>Ketogenic diet </li></ul></ul><ul><ul><li>Classical ketogenic diet </li></ul></ul><ul><ul><li>MCT diet </li></ul></ul><ul><ul><li>Atkins diet </li></ul></ul><ul><ul><li>Oligoantigenic diet </li></ul></ul>
  • 6. <ul><li>Epilepsy Surgery Techniques </li></ul><ul><ul><li>Lesional surgery (for example, tumour, amygdalo-hippocampectomy, temporal lobectomy, extra-temporal resections, anatomical hemispherectomy or functional hemispherotomy, removal of cortical seizure foci) </li></ul></ul><ul><ul><li>Specific surgical techniques (for example, sub-pial transection for Landau-Kleffner syndrome) </li></ul></ul><ul><ul><li>Palliative surgery (for example, callosotomy or vagus nerve stimulator implantation) </li></ul></ul>Non conventional antiepileptic drug (AED) treatment of Epilepsy contd.
  • 7. Non-pharmacological treatment of epilepsy <ul><li>Lifestyle changes </li></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Avoidance of sleep deprivation </li></ul></ul><ul><ul><li>Avoidance of excessive alcohol consumption </li></ul></ul><ul><li>Psychological approaches </li></ul><ul><ul><li>Techniques to abort seizures or reduce seizure frequency (for example, avoidance, relaxation, biofeedback, aversive therapy) </li></ul></ul><ul><ul><li>Promotion of emotional wellbeing </li></ul></ul><ul><ul><li>(for example, Yoga) </li></ul></ul><ul><ul><li>Reduction of psychiatric co-morbidity </li></ul></ul><ul><ul><li>(for example, anxiety or depression) </li></ul></ul><ul><ul><li>Coping strategies for living with epilepsy </li></ul></ul><ul><ul><li>(for example, CBT, counseling, psychotherapy, educational interventions ) </li></ul></ul>
  • 8. Non-pharmacological treatment of epilepsy (contd.) <ul><li>Alternative therapy </li></ul><ul><ul><li>Herbal medicine </li></ul></ul><ul><ul><li>Homeopathy </li></ul></ul><ul><li>Others </li></ul><ul><ul><li>Aromatherapy </li></ul></ul><ul><ul><li>Hypnosis </li></ul></ul><ul><ul><li>Acupuncture </li></ul></ul><ul><ul><li>Seizure alert dogs </li></ul></ul>
  • 9. <ul><li>1958 – Intramuscular ACTH in West Syndrome </li></ul><ul><li>Tetracosactide (UK) </li></ul><ul><li>Hydrocortisone (France) </li></ul><ul><li>Prednisolone </li></ul><ul><li>Also effective in – Non convulsive Status epilepticus, severe myoclonic epilepsy of infancy, Lennox-Gastaut syndrome, Rasmussen’s Syndrome, Landau-Kleffner syndrome </li></ul><ul><li>Prednisolone – 2-3 mg/kg/day x 2 weeks, taper over 1-2 weeks </li></ul><ul><li>Mechanism – Not clear </li></ul>Non conventional Medical treatments Corticosteroids
  • 10. Non conventional Medical treatments Immunoglobulin <ul><li>1970- IVI g G for Allergic rhinitis -Epilepsy improved </li></ul><ul><li>Tried in – West Syndrome, LGS, RS </li></ul><ul><li>Dose – 100- 1000 mg / kg x 3 days, repeated after 1,2,3 week </li></ul><ul><li>Mechanism – Not clear </li></ul><ul><li>Expensive </li></ul><ul><ul><li>Weak evidence </li></ul></ul>
  • 11. Melatonin <ul><li>Chronobiotic hormone secreted by pineal gland - regulates circadian rhythym </li></ul><ul><li>May improve Myoclonic & nocturnal seizures </li></ul><ul><li>Mechanism – Improved sleep quality / Neuro protection </li></ul>
  • 12. Vitamins & Epilepsy <ul><li>AEDs may lower plasma levels of Vitamins especially Vitamin-D </li></ul><ul><li>General Indication of Vitamins </li></ul><ul><ul><li>Replacement therapy in inherited metabolic defects </li></ul></ul><ul><ul><li>Presumed anticonvulsant role possibly by resetting GABA & glutaminergic systems </li></ul></ul>
  • 13. Pyridoxine (Vitamin-B6) <ul><li>Recessive pyridoxine dependant seizure syndrome </li></ul><ul><li>Diagnosis- clinical, intractable seizures under 18 months </li></ul><ul><li>Oral Pyridoxine 100-200 mg daily, intravenous 100 mg (watch for Respiratory arrest) </li></ul>
  • 14. Pyridoxal phosphate <ul><li>Major activated form of Vit.-B6 </li></ul><ul><li>Infantile spasms, early infantile epileptic encephalopathy (Ohtahara’s syndrome) </li></ul><ul><li>50 mg/kg/day x 2 weeks </li></ul>
  • 15. Biotin <ul><li>Biotinidase deficiency – AR (Rare) </li></ul><ul><li>Treatable leucoencephalopaty in infants and young children, intractable seizures </li></ul><ul><li>Dose - 5-20 mg Biotin supplementation daily </li></ul>
  • 16. Folinic acid <ul><li>Seizures in neonate patients not responding to AEDs, Pyridoxine, Biotin </li></ul><ul><li>Rare inherited syndrome </li></ul><ul><li>Folinic acid 5-10 mg daily </li></ul>
  • 17. Ketogenic Diet (KD) <ul><li>Devised in 1920s, interest reawakened in 1990s </li></ul><ul><li>Mimics fasting by having high Fat & low Carbohydrate content promoting prolonged ketone production </li></ul><ul><li>Mechanism- Not understood </li></ul><ul><li>Indication - Effective alternative therapy for intractable epilepsy/unacceptable AED toxicity or both </li></ul>
  • 18. Overview of admission of the ketogenic diet <ul><li>Day Care </li></ul><ul><li>Minus1 History / physical </li></ul><ul><li>Day1 Admit to hospital </li></ul><ul><li> Dextrostix every 6h; if<40mg/dl every 2h; Glucose <25 mg/ dl give 30 ml orange juice; follow </li></ul><ul><li> Use carbohydrate- free medications </li></ul><ul><li>Day2 Continue monitoring </li></ul><ul><li>Nutrition </li></ul><ul><li>Begin fasting after dinner </li></ul><ul><li>Fast </li></ul><ul><li>Fluids restricted to </li></ul><ul><li>60-75 ml/kg per day; encourage drinking </li></ul><ul><li>Continue fluids </li></ul><ul><li>Fast until dinner then 1/3 of the usual calories </li></ul>
  • 19. <ul><li>Day Care </li></ul><ul><li>Day3 Continue monitoring until tolerating meals </li></ul><ul><li>Day 4 Continue monitoring </li></ul><ul><li>Day 5 Discharge reivew : medications, vitamins, monitoring, follow-up </li></ul><ul><li>Nutrition </li></ul><ul><li>Continue fluids </li></ul><ul><li>Breakfast and lunch: 1/3 of calculated meal </li></ul><ul><li>Dinner : 2/3 of calculated meal </li></ul><ul><li>Breakfast and lunch : 2/3 of calculated meal </li></ul><ul><li>Dinner: Full ketogenic diet meal </li></ul><ul><li>Breakfast : Full ketogenic diet meal </li></ul>Overview of admission of the ketogenic diet contd.
  • 20. Ketogenic diet <ul><li>Discontinue if patient seizure free for 2 years </li></ul><ul><li>Problems </li></ul><ul><ul><li>Parent commitment </li></ul></ul><ul><ul><li>Patient compliance </li></ul></ul><ul><ul><li>Frequent blood/urine monitoring </li></ul></ul><ul><ul><li>Loss of effect after many months </li></ul></ul>
  • 21. Ketogenic diet <ul><li>Side effects </li></ul><ul><ul><li>GI upset </li></ul></ul><ul><ul><li>Weight loss </li></ul></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><li>Hypernatremia </li></ul></ul><ul><ul><li>Vitamin & trace element deficiency </li></ul></ul><ul><ul><li>Renal stone </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>Atherosclerosis </li></ul></ul>
  • 22. Atkins diet <ul><li>Popular in UK for weight reduction </li></ul><ul><li>Lower fat and high protein content- No fluid or calorie restriction and no fast in beginning </li></ul><ul><li>Single trial (2003)- benefit </li></ul><ul><li>Easier to implement and sustain </li></ul>
  • 23. Oligoantigenic diet <ul><li>Diet containing one meat, one starch, one fruit, one vegetable, one oil, multivitamins, calcium and mineral water </li></ul><ul><li>Headache and seizure frequency improved (J. pediatrics1989) </li></ul><ul><li>Unlikely to become as recognized as KD </li></ul>
  • 24. Epilepsy surgery <ul><li>Resective surgery </li></ul><ul><li>Disconnective Surgery </li></ul>
  • 25. Epilepsy Surgery <ul><li>Selection process – 3 steps </li></ul><ul><li>Establish epileptic nature and intractability </li></ul><ul><li>Match the patient to one on remediable syndromes </li></ul><ul><ul><li>Mesiall Temporal epilepsy </li></ul></ul><ul><ul><li>Lesional partial epilepsy </li></ul></ul><ul><ul><li>Diffuse hemisphiric syndrome </li></ul></ul><ul><ul><li>Secondary generalized epilepsy in infants and Children </li></ul></ul><ul><ul><li>Sec. generalized epilepsy in older patients </li></ul></ul><ul><li>Consider functional intervention if not suitable for resective surgery </li></ul>
  • 26. Epilepsy surgery : work up <ul><li>Clinical History </li></ul><ul><li>Neuro Radiological investigations </li></ul><ul><ul><li>MRI (epilepsy protocol) </li></ul></ul><ul><ul><li>SPECT </li></ul></ul><ul><ul><li>PET </li></ul></ul><ul><ul><li>fMRI </li></ul></ul><ul><li>Neurophysiological investigations </li></ul><ul><ul><li>EEG </li></ul></ul><ul><ul><li>Video Telemetry </li></ul></ul><ul><li>Neuro psychological investigations </li></ul><ul><li>Quality of life and psychiatric assessments esp. in older childrem </li></ul>
  • 27. Vagal Nerve stimulation (VNS) <ul><li>1960- Vagal stimulation influenced EEG activity </li></ul><ul><li>1992- (Zabara et al)- vegal stimulation controlled seizures in dogs induced by IV Phenyalnetetrazole </li></ul><ul><li>Approved in USA for refractory partial seizure in > 12 yrs old patients. Europe- any age or seizure type </li></ul>
  • 28. Vagal nerve Stimulation (VNS) <ul><li>Left vagal nerve stimulation - fibers predominantly afferent </li></ul><ul><li>Adverse effects- Fever, cough, headache, voice alteration, cough/cold, infection, pharyngitis </li></ul><ul><li>MRI Body – contraindicated. </li></ul><ul><ul><li>MRI Head- can be performed using closed head coil </li></ul></ul>
  • 29. Non pharmacological treatment Lifestyle changes : Exercise <ul><li>Impact on quality of life and social inclusion rather than seizure control </li></ul><ul><li>One trial in adults (1990)- no difference in seizure frequency after 4 weeks of aerobic exercises. </li></ul><ul><li>No RCT </li></ul>
  • 30. Sleep hygiene <ul><li>Adequate sleep </li></ul><ul><ul><li>Sleep later, get up later </li></ul></ul><ul><li>Idiopathic generalized seizures, JME, Temporal lobe epilepsies </li></ul>
  • 31. Alcohol <ul><li>Seizures within 48 Hours of excessive / binge drinking </li></ul><ul><li>Alcohol Disturbed sleep Seizure precipitation </li></ul>
  • 32. Psychological approaches Avoidance <ul><li>Triggers – Photosensitive seizures (light), music, eating, reading, hot water, chess playing, hair brushing </li></ul><ul><li>Photosensitive epilepsy – Avoidance Techniques </li></ul><ul><ul><li>Sitting more than 2.5 meter from TV in well-lit room </li></ul></ul><ul><ul><li>Use remote control </li></ul></ul><ul><ul><li>Approach TV with one eye close </li></ul></ul><ul><ul><li>Avoid playing video games in darkened room </li></ul></ul>
  • 33. Relaxation technique <ul><li>Only one RCT in children (Dahe,1985)- only 18 patients- no firm conclusion </li></ul><ul><li>May improve seizures through improved sleep </li></ul>
  • 34. Biofeedback <ul><li>Popular psychological tool since 1970s </li></ul><ul><li>Patient trained to increase certain frequencies (12-14 Hz) on EEG from sensory motor cortex (sensory motor rhythm) </li></ul><ul><li>Known to inhibit seizures in animals </li></ul><ul><li>Positive visual feed back with colored lights and images- 30 minutes training several times / week for 3 months </li></ul><ul><li>Cumbersome impractical for young or cognitively impaired children </li></ul>
  • 35. Promotion of emotional well being Yoga <ul><li>Stress – seizure precipitant </li></ul><ul><li>Yoga – Believed to induce relaxation / stress reduction involves breathing exercise, postures, meditation techniques </li></ul><ul><li>Only one RCT (Ramaratnam et al,2000)- 10 patients “Sahaja yoga” 10 “Sham” yoga, 12 control. Study small- no useful conclusion </li></ul><ul><li>Yoga – unlikely to play role in pediatric population </li></ul>
  • 36. Reduction in Psychiatric Co-morbidity <ul><li>Anxiety, Depression, Psychosis may complicate epilepsy </li></ul><ul><li>Antidepressants and Neuroleptics wherever indicated </li></ul>
  • 37. Educational interventions <ul><li>Residential Education programmes improves quality of life </li></ul><ul><ul><li>Improvement in knowledge and understanding of Epilepsy </li></ul></ul><ul><ul><li>Coping with Epilepsy </li></ul></ul><ul><ul><li>Medicine compliance </li></ul></ul><ul><ul><li>Improves social skills, scholistic performance </li></ul></ul>
  • 38. Alternate (complimentary) therapies Herbal medicine & Homeopathy <ul><li>No RCT </li></ul><ul><li>Open label studies (Tyagi et al,2003) </li></ul><ul><ul><li>Remedy containing 13 herbs in 100 patients had similar efficacy as phenobarbitone 3-6 mg/kg </li></ul></ul><ul><ul><li>Herb “Zhenxianling” (constituents -peach flower buds and human placenta) given to 239 patients for 6 months to 2 yrs. seizure reduction of > 75% in two third </li></ul></ul><ul><li>Lack of scientific studies- can’t be recommended </li></ul>
  • 39. Aromatherapy and Hypnosis <ul><li>Betts et al 2003 – open study of 100 patients- one third became seizure free for 12 months when both techniques were used together </li></ul><ul><li>Time consuming </li></ul><ul><li>Hypnosis- useful in children and adults to induce non epileptic seizures </li></ul>
  • 40. Acupuncture <ul><li>2 RCTs in adults (Klentz et al 1999, steven et al,2000) all patients had drug resistant epilepsy. </li></ul><ul><ul><li>Acupuncture v/s sham acupuncture no difference found </li></ul></ul><ul><li>Acupuncture unlikely to ever have a role in pediatric epilepsy </li></ul>
  • 41. Conclusion <ul><li>Seizure control achieved in 75% children with conventional AEDs </li></ul><ul><li>Tempting for parents to seek alternative non conventional AEDs and non pharmacological treatment for children with intractable epilepsy/ drug toxicity </li></ul><ul><li>Alternative or complementary medicine become popular, though not scientific , for many chronic illnesses where Allopathy has frustrating lack of efficacy </li></ul>
  • 42. Conclusion <ul><li>Only ketogenic diet and Epilepsy surgery have strong evidence base and are effective </li></ul><ul><li>More time should be spent to educate families about nature of disease and poor prognosis , rather than advocating use of unproven remedies or alternative approaches </li></ul>
  • 43. THANKS

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