Tapan Audhya, PhD New York University, NY & Vitamin Diagnostics, NJ

1. Autism One 2009 Conference Chicago, IL. May, 2009 Unprovoked Seizures in Autistic Individuals Tapan Audhya, PhD New York University, NY & Vitamin Diagnostics, NJ

2. Seizure (Sudden, Abnormal electrical activity in brain) Generalized seizure (Both site of brain) Unconscious; Both tonic and clonic Partial seizure (Focal, sensory or petit mal) (one part of brain; particularly the site which directs “flight” response; conscious; either tonic or clonic) Simple (No loss of consciousness) Complex Epilepsy – a recurrent seizure Non-epileptic Seizure – Similar to epileptic. Seizure but not caused by electrical disruption of cerebral cortex. Classified as 1) physiologic or 2) psychogenic

3. Age Group 4 -16 years ; N = 89 (Boys - 66, Girls – 23) Repetitive Epileptic Seizure 1-7.2 min (mean – 4.0 min) 3 - 4 times a day ICD-9 → 345.4;345.9;343.4;299.0 Epileptic Seizure was confirmed by EEG on 29 boys and 5 girls 17 children had spinal tap for unrelated reason Nutritional Status of Autistic Children with Seizure

4. Vitamins & Minerals

5. Protein & Amino Acids Prolactin 199 amino acid, Hypothalamic peptide & controlled by Dopamine 21 boys and 3 girls had high plasma prolactin (2 -3x the normal levels) 11 boys & 3 girls had low Dopamine Glutamate 14/17 high glutamate in CSF, 42 high in Plasma Aspertate 14 high in Plasma & CSF Taurine 10/17 low in CSF, 34 low in Plasma GABA 13/17 low in CSF, 28 high in Plasma, 59 low in Plasma

6. Synthesis of GABA and α-Ketoglutarate Glutamine → Glutamate Decarboxylase GABA P-5-P Transaminase α-Ketoglutarate P-5-P

7. Glutathione Peroxidase 26 low normal 34 less than half the normal value Free Radical Oxygen SOD H202 Glutathione Peroxidase (GP) H20 + 02 GP GSSG GSH GR

8. Autism, Seizure & Neurotransmitters (NT) NTs are chemicals that transfer information from one neuron to another • NTs have two basic functions • Inform receiving neuron to “Fire” Excitatory • Inform receiving neuron to stop “Firing” Inhibitory These actions of NTs depend on a class of proteins which is known as receptors. These receptors initiate the activity after receiving the NTs. GABA, for example, binds to receptors which are inhibitory. Most anti anxiety medications increase GABA transmission More GABA receptor activation Shut down the CNS Relaxation

9. GABA Receptor • GABAergic system in cerebellum and limbic structure in affected in autism. Inhibition of this system is suppressed by • Impairment of GABA-receptor • Antagonism of GABAergic neurons bearing receptors sensitive to glutamate analog NMDA. • Example: • Pathology relating to GABA receptors and suspected etiologies of autism • Excessive glutamate activation of non-NMDA glutamate receptor – Pathology observed in Autism

10. GABA Receptor submit Genes in Autism Only GABR A4 is involved in the etiology of autism and gene – gene interaction between GABR A4 and GABR B1

11. GABAA Receptor

12. GABAA Receptor

13. Controlling Seizures by Nutritional Approach Ketogenic Diet : A diet high in fats, low in protein and carbohydrate. Fat: (carb + protein) = 4:1 However, never make too low carb (Hypoglycemia) Mediumchain Triglycerides (MCT) are more ketogenic.