Alternative approaches to conventional antiepileptic drugs in the management of pediatric epilepsy Dr. Vijay Sardana MD,DM...
Epilepsy- Pharmacological treatments <ul><li>1850s-Bromides </li></ul><ul><li>1912-Phenobarbital </li></ul><ul><li>Last 2 ...
<ul><li>Seizure control achieved in 75 % children with conventional AEDs </li></ul><ul><li>Increasing concern amongst pare...
Non conventional methods <ul><li>Evidence base  </li></ul><ul><ul><li>non randomized uncontrolled trials </li></ul></ul><u...
Non conventional antiepileptic drug (AED) treatment of Epilepsy <ul><li>Non-AED medical treatment </li></ul><ul><ul><li>St...
<ul><li>Epilepsy Surgery Techniques </li></ul><ul><ul><li>Lesional surgery (for example, tumour, amygdalo-hippocampectomy,...
Non-pharmacological treatment of epilepsy <ul><li>Lifestyle changes </li></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul>...
Non-pharmacological treatment of epilepsy (contd.) <ul><li>Alternative therapy </li></ul><ul><ul><li>Herbal medicine </li>...
<ul><li>1958 – Intramuscular ACTH in West Syndrome </li></ul><ul><li>Tetracosactide (UK) </li></ul><ul><li>Hydrocortisone ...
Non conventional Medical treatments Immunoglobulin <ul><li>1970- IVI g G for Allergic rhinitis -Epilepsy improved </li></u...
Melatonin <ul><li>Chronobiotic hormone secreted by pineal gland - regulates  circadian rhythym </li></ul><ul><li>May impro...
Vitamins & Epilepsy <ul><li>AEDs may lower plasma levels of Vitamins especially Vitamin-D </li></ul><ul><li>General Indica...
Pyridoxine (Vitamin-B6) <ul><li>Recessive pyridoxine dependant seizure syndrome </li></ul><ul><li>Diagnosis- clinical, int...
Pyridoxal phosphate <ul><li>Major activated form of Vit.-B6 </li></ul><ul><li>Infantile spasms, early infantile epileptic ...
Biotin <ul><li>Biotinidase deficiency – AR (Rare) </li></ul><ul><li>Treatable leucoencephalopaty  in infants and young chi...
Folinic acid <ul><li>Seizures in neonate patients not responding to AEDs, Pyridoxine, Biotin </li></ul><ul><li>Rare inheri...
Ketogenic Diet (KD) <ul><li>Devised in 1920s, interest reawakened in 1990s </li></ul><ul><li>Mimics fasting by having high...
Overview of admission of the ketogenic diet <ul><li>Day  Care </li></ul><ul><li>Minus1   History / physical </li></ul><ul>...
<ul><li>Day    Care  </li></ul><ul><li>Day3   Continue  monitoring until  tolerating meals </li></ul><ul><li>Day 4   Conti...
Ketogenic diet <ul><li>Discontinue if patient seizure free for 2 years </li></ul><ul><li>Problems </li></ul><ul><ul><li>Pa...
Ketogenic diet <ul><li>Side effects </li></ul><ul><ul><li>GI upset </li></ul></ul><ul><ul><li>Weight loss </li></ul></ul><...
Atkins diet <ul><li>Popular in UK for weight reduction </li></ul><ul><li>Lower fat and high protein content- No fluid or c...
Oligoantigenic diet <ul><li>Diet containing one meat, one  starch, one fruit, one vegetable, one oil, multivitamins, calci...
Epilepsy surgery <ul><li>Resective surgery </li></ul><ul><li>Disconnective Surgery  </li></ul>
Epilepsy Surgery <ul><li>Selection process – 3 steps </li></ul><ul><li>Establish epileptic nature and intractability </li>...
Epilepsy surgery : work up <ul><li>Clinical History </li></ul><ul><li>Neuro Radiological investigations  </li></ul><ul><ul...
Vagal Nerve stimulation (VNS) <ul><li>1960- Vagal stimulation influenced EEG activity </li></ul><ul><li>1992- (Zabara et a...
Vagal nerve Stimulation (VNS) <ul><li>Left vagal nerve stimulation - fibers predominantly afferent </li></ul><ul><li>Adver...
Non pharmacological treatment Lifestyle changes : Exercise   <ul><li>Impact on quality of life and social inclusion rather...
Sleep hygiene <ul><li>Adequate sleep </li></ul><ul><ul><li>Sleep later, get up later </li></ul></ul><ul><li>Idiopathic gen...
Alcohol <ul><li>Seizures within 48 Hours of excessive / binge drinking </li></ul><ul><li>Alcohol  Disturbed sleep  Seizure...
Psychological approaches Avoidance <ul><li>Triggers – Photosensitive seizures (light), music, eating, reading, hot water, ...
Relaxation technique <ul><li>Only one RCT in children (Dahe,1985)- only 18 patients- no firm conclusion </li></ul><ul><li>...
Biofeedback <ul><li>Popular psychological tool since 1970s </li></ul><ul><li>Patient trained to increase certain frequenci...
Promotion of emotional well being Yoga <ul><li>Stress – seizure precipitant </li></ul><ul><li>Yoga – Believed to induce re...
Reduction in Psychiatric  Co-morbidity <ul><li>Anxiety, Depression, Psychosis may complicate epilepsy </li></ul><ul><li>An...
Educational interventions  <ul><li>Residential Education programmes  improves quality of life </li></ul><ul><ul><li>Improv...
Alternate (complimentary) therapies Herbal medicine & Homeopathy <ul><li>No RCT </li></ul><ul><li>Open label studies (Tyag...
Aromatherapy and Hypnosis <ul><li>Betts et al 2003 – open study of 100 patients- one third became seizure free for 12 mont...
Acupuncture <ul><li>2 RCTs in adults (Klentz et al 1999, steven et al,2000) all patients had drug resistant epilepsy.  </l...
Conclusion <ul><li>Seizure control achieved in 75% children with conventional AEDs </li></ul><ul><li>Tempting for parents ...
Conclusion <ul><li>Only ketogenic diet and Epilepsy surgery have strong evidence base and are effective </li></ul><ul><li>...
THANKS
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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

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 24. Epilepsy surgery <ul><li>Resective surgery </li></ul><ul><li>Disconnective Surgery </li></ul>
  25. 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. 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. 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. 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. 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. 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. 31. Alcohol <ul><li>Seizures within 48 Hours of excessive / binge drinking </li></ul><ul><li>Alcohol Disturbed sleep Seizure precipitation </li></ul>
  32. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 43. THANKS

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