Epilepsy in Autism: An Overview

Autism One Conference Toronto, Canada Oct. – Nov. 2009 www.hardyhealthcare.com drhardy@hardyhealthcare.com 781-740-8300 HHA Epilepsy in Autism: An Overview

HHA A Time for Optimism 32 year perspective • Back wards of a 1300 bed state school for the MR • Began to suspect complex partial szs • If not on EEG, do not rx. • Rigidity of thinking is changing.

HHA An Integrative Approach • Attention to diets and nutrition • Attention to environmental factors • Vaccines • Mercury • Attention to allergies, oxidative stress, inflammation, and detoxification

HHA Epidemiology is Different in Autism • Incidence of epilepsy is higher in autism • M. Rutter in 1970 stated @ one third • 20% to 40% is current estimate • Abnormal EEGs – up to 84% • Higher incidence of vaccination-induced seizures: • Pertussis, etc. • Higher incidence of temporal lobe seizure (TLE or CPS)

HHA Morbidity is Increased • Impaired or delayed language • Impaired or delayed cognition • Secondary emotional symptoms Anxiety, fear, obsessionalism • Social impairments Helmets, unable to swim at times • Anxiety in parents and staff of programs

HHA Look for Comorbidity • Co-morbid diseases • Tuberous Sclerosis • Fragile-X syndrome • Mesial-temporal sclerosis • Rubella • Neruo-inflammatory conditions? • Mitochondrial disorders • Unrecognized nutritional or metabolic issues: functional folic acid deficiency • Neuro-toxins: heavy metals?, etc.

HHA Mortality: Increased • Few studies on this subject (? avoidance) • SIDS • Sudden Unexplained Death in Epilepsy (SUDEP) • Cardio-respiratory event • Early morning nocturnal seizures • Aspiration • Trauma • Drowning

HHA Diagnosis: More Difficult • Often non-verbal or limited ability to express symptom, especially emotional feelings • Often unable to cooperate for EEGs, BEAMs, QEEGs, MEGs • Seizure vs: inattention, tics, Sydenham’s chorea, ‘stereotypy of autism’, PANDAS • Subclinical discharges & occult szs

HHA Clinical History is Key! • Temporal and paroxysmal patterns • History, history, history • Location, location, location • Trauma: birth or other head traumas • Mesial-temporal sclerosis • Constellation of symptoms and signs • Family history of variable importance • Myoclonic epilepsy • Mitochondrial disorders

HHA Examination • Neurocutaneous disorders • Dysmorphic features suggestive of chromosomal disorder or genetic disorder • Fetal alcohol syndrome • Valproate syndrome

HHA Laboratory Testing • Neurophysiologic • Sensitivity and specificity • Imaging studies • Genetic • Metabolic • Toxicological • Oxidative stress, sulfation, methylation • The Therapeutic Trial

HHA Basic Adage • “If you do not know the diagnosis after taking the history and doing the exam, go back and take the history over again.” • Robert Joynt, MD, PhD.

HHA Epilepsy Classification • Generalized (both hemispheres involved) • Tonic-clonic (Grand Mal, major motor) • Petite Mal (Absence seizure) • Partial • Simple: one modality of brain function • Complex: two or more • Temporal Lobe Epilepsy • Secondary Generalization • Myoclonic Epilepsy.

HHA Special Syndromes in ASD • TLE: + Panic Disorder +/- OCD • Landau-Kleffner Syndrome (epileptic aphasia): role of inflammation or oxidative stress? • Post Vaccination Epilepsy • Cerebral Folate Deficiency

HHA

HHA Travolta Case • Kawasaki’s Disease – mucocutaneous lymph node syndrome “not associated with either autism or epilepsy”. • BUT note the signs and symptoms of KD: • High fever lasting for five days or longer • Pinkeye in both eyes • Redness of lips, tongue, and lining of mouth • Swollen cervical lymph node > 1.5 mm in diameter • Red rash on the body, which may be flat or bumpy and that may have variable pattern • Swollen hands and feet with redness of palm and soles. In second week there may be peeling of the skin starting around the fingernails and moving up the arms

HHA Kawasaki’s Disease, Acrodynia, and Mercury • Mercury may play a pathogenic role • High urine mercury • Overlap of symptoms in two syndromes • Genetic depletion of glutathione S-transferase • Onset often within days of vaccination • 1985 – 1997 20x in incidence, paralleling use of thimerosal • Mutter J & Yeter D. Curr Med Chem. 2008; 15(28):3000-10.

HHA Pre-ictal • The build up of tension/agitation • Deepening of mood or depression • Increase of anxiety • Heightening of mania or obsessions and compulsions • Exacerbation of psychosis • Therapeutic effect of seizures

HHA Partial Ictal Phenomena • Motor Symptoms • Focal motor activity anywhere on body • Speech arrest • Somato-sensory and Special Sensory Hallucinations • Somato-sensory • Unformed visual • Olfactory • Gustatory • Vertiginous-vestibular

HHA Partial Ictal Phenomena,Continued • Derealization • Speeding thoughts • Incoherence of thought • Distortions of: • Time • Body Image • Odor • Sound • Color • Size, shape, distance • Hallucinations • Mystical experience • Psychic-Cognitive Symptoms • Fear, Anxiety, Panic • Depression • Anger • Irritability • Pleasure • Dysphasia • Deja vu • Jamais vu

HHA Partial Ictal Phenomena,Continued • Autonomic Symptoms • Abdominal: nausea • Chest • Unusual head • Hyper-salivation • Diaphoresis • Temperature • Pallor or flushing • Piloerection • Palpitations

HHA Post-ictal • Aggression • Self-injury • Confusion, Delirium • Lethargy, Anergy, Somulence

HHA Interictal • Aggression • Psychosis (Schizophreniform) • Sexual Dysfunction • Religiosity and Philosophic Interests • Hypergraphia • Circumstantiality and Viscosity (“stickiness”)

HHA Interictal Period “The Epileptic Personality” • Obsessiveness • Viscosity • Emotionality • Circumstantiality • Paranoia • Depression • Altered Sexual Interest • Anger • Aggression • Dependence • Religiosity • Hypermorality • Increased philosophic Concerns

HHA Panic Disorder Temporal Lobe Epilepsy TLE & Panic Attacks & SIB

HHA TLE & Panic and SIB HHA

HHA Biomedical Interventions • NUTRICEUTICAL • HORMONAL • Natural progesteron • Be careful of synthetic progestins & Provera • PHARMACEUTICAL • NEUROFEEDBACK • DETOXIFICATION: +/- CHELATION • VAGUS NERVE STIMULATION • NEUROSURGERY

HHA Treatment Should Be Iterative • “Trial and Error” • “Willing to stick one’s neck out” - to be inventive

HHA Coups in Boston  • 7 y/o girl with spikes on EEG, absent AER, probable regressive autism, side effects from Depakote (sedation) and Lamictal (rash), and fear of trying prednisone due to side effects: “I told her (mother) that I am more inclined to think that the treatments which Dr. Hardy may prescribe might actually do more for her and be safer in the long run. Thus, I thought it made a lot more sense to pursue that route first.” • David L. Coulter, M. D., Harvard Medical School, December 2008

HHA Nutritional/Natural Treatments I • Diets • Ketogenic (since 1921) • Atkins Diet? • Casein-free and/or gluten-free • Hormonal • Natural progesterone • Pills • Lozenge • Creams (ProGest)

HHA Nutritional/Natural Treatments II • L-Carnitine (to prevent valproate toxicity) • Magnesium (pre-eclampsia) • Zinc • Omega-3 EFAs • Vitamin B6 as P-5-P • L-methylfolinic acid: Deplin & CerefolinNAC

HHA Nutritional/Natural Treatments III • Mitochondrial cocktails • Vitamins D, E, thiamine, biotin, B12 • Manganese • DMG and/or TMG • Sulfur as ALA, glutathione, MSM, DMSA

HHA Antiepileptic Medication I • First Generation (1930 – 1980) – all associated with side effects (especially folate deficiency) and adverse drug-drug interactions • Bromides • Barbituates • Phenytoin • Carbamazepine • Valproic acids • ACTH & steroids

HHA Antiepileptic Medication II • Second generation (1990 – 2002) - fewer side effects • Neurontin • Lamictal • Topamax • Gabatril • Zonagran • Keppra – “The B6 discovery!” • Lyrica

HHA The B6 Discovery  • Vit B6 found to reduce behavioral side effects from Keppra

HHA Antiepileptic Medication III • Third generation in phase 3 Trials (2009 – ?) • Carisbamate • Retigabine • Eslicarbazepine • Lacosamide

HHA Vagal Nerve Stimulation

HHA Questions

Epilepsy in Autism: An Overview