Epilepsy in Autism: An Overview
Autism One Conference
Toronto, Canada
Oct. – Nov. 2009
781-740-8300Nov. 09 1HHA
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.
Nov. 09 2HHA
An Integrative Approach
Attention to diets and nutritionAttention to environmental factors
Vaccines Mercury
Attention to allergies, oxidative stress, inflammation, and detoxification
Nov. 09 3HHA
Epidemiology is Different in AutismIncidence 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)
Nov. 09 4HHA
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
Nov. 09 5HHA
Look for ComorbidityCo-morbid diseases
Tuberous Sclerosis Fragile-X syndrome Mesial-temporal sclerosis Rubella Neruo-inflammatory conditions?
Mitochondrial disordersUnrecognized nutritional or metabolic
issues: functional folic acid deficiencyNeuro-toxins: heavy metals?, etc.
Nov. 09 6HHA
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
Nov. 09 7HHA
Diagnosis: More DifficultOften 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
Nov. 09 8HHA
Clinical History is Key!
Temporal and paroxysmal patternsHistory, history, historyLocation, location, location
Trauma: birth or other head traumas Mesial-temporal sclerosis
Constellation of symptoms and signsFamily history of variable importance
Myoclonic epilepsy Mitochondrial disorders
Nov. 09 9HHA
Examination
Neurocutaneous disordersDysmorphic features suggestive
of chromosomal disorder or genetic disorder
Fetal alcohol syndromeValproate syndrome
Nov. 09 10HHA
Laboratory TestingNeurophysiologic
Sensitivity and specificity
Imaging studiesGeneticMetabolicToxicologicalOxidative stress, sulfation, methylationThe Therapeutic Trial
Nov. 09 11HHA
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.
Nov. 09 12HHA
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.Nov. 09 13HHA
Special Syndromes in ASD
TLE: + Panic Disorder +/- OCDLandau-Kleffner Syndrome (epileptic
aphasia): role of inflammation or oxidative stress?
Post Vaccination EpilepsyCerebral Folate Deficiency
Nov. 09 14HHA
Nov. 09 15HHA
Travolta CaseKawasaki’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
Nov. 09 16HHA
Kawasaki’s Disease, Acrodynia, and Mercury
Mercury may play a pathogenic roleHigh urine mercuryOverlap of symptoms in two syndromesGenetic depletion of glutathione S-transferaseOnset often within days of vaccination1985 – 1997 20x in incidence, paralleling use of
thimerosal Mutter J & Yeter D. Curr Med Chem. 2008;
15(28):3000-10.
Nov. 09 17HHA
Pre-ictal
The build up of tension/agitationDeepening of mood or depressionIncrease of anxietyHeightening of mania or obsessions and
compulsionsExacerbation of psychosisTherapeutic effect of seizures
Nov. 09 18HHA
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
Nov. 09 19HHA
Partial Ictal Phenomena,Continued
Psychic-Cognitive Symptoms Fear, Anxiety, Panic Depression Anger Irritability Pleasure Dysphasia Deja vu Jamais vu
Derealization Speeding thoughts Incoherence of thought Distortions of:
TimeBody ImageOdorSoundColorSize, shape, distance
Hallucinations Mystical experience
Nov. 09 20HHA
Partial Ictal Phenomena,Continued
Autonomic Symptoms Abdominal: nausea Chest Unusual head Hyper-salivation Diaphoresis Temperature Pallor or flushing Piloerection Palpitations
Nov. 09 21HHA
Post-ictal
AggressionSelf-injuryConfusion, DeliriumLethargy, Anergy, Somulence
Nov. 09 22HHA
Interictal
AggressionPsychosis (Schizophreniform)Sexual DysfunctionReligiosity and Philosophic InterestsHypergraphiaCircumstantiality and Viscosity
(“stickiness”)
Nov. 09 23HHA
Interictal Period “The Epileptic Personality”
ObsessivenessViscosityEmotionalityCircumstantialityParanoiaDepressionAltered Sexual
Interest
AngerAggressionDependenceReligiosityHypermoralityIncreased
philosophic Concerns
Nov. 09 24HHA
TLE & Panic Attacks & SIB
Temporal LobeEpilepsy
Panic Disorder
Nov. 09 25HHA
HHA
TLE & Panic and SIB
Nov. 09 26HHA
Biomedical Interventions
NUTRICEUTICAL HORMONAL
Natural progesteronBe careful of synthetic progestins & Provera
PHARMACEUTICALNEUROFEEDBACKDETOXIFICATION: +/- CHELATIONVAGUS NERVE STIMULATION NEUROSURGERY
Nov. 09 27HHA
Treatment Should Be Iterative
“Trial and Error”
“Willing to stick one’s neck out” - to be inventive
Nov. 09 28HHA
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
Nov. 09 29HHA
Nutritional/Natural Treatments IDiets
Ketogenic (since 1921) Atkins Diet? Casein-free and/or gluten-free
Hormonal Natural progesterone
Pills Lozenge Creams (ProGest)
Nov. 09 30HHA
Nutritional/Natural Treatments II
L-Carnitine (to prevent valproate toxicity)Magnesium (pre-eclampsia)ZincOmega-3 EFAsVitamin B6 as P-5-PL-methylfolinic acid: Deplin &
CerefolinNAC
Nov. 09 31HHA
Nutritional/Natural Treatments III
Mitochondrial cocktailsVitamins D, E, thiamine, biotin, B12Manganese DMG and/or TMGSulfur as ALA, glutathione, MSM, DMSA
Nov. 09 32HHA
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
Nov. 09 33HHA
Antiepileptic Medication IISecond generation (1990 – 2002) - fewer side effects
Neurontin Lamictal Topamax Gabatril Zonagran Keppra – “The B6 discovery!” Lyrica
Nov. 09 34HHA
The B6 Discovery
• Vit B6 found to reduce behavioral side effects from Keppra
Nov. 09 35HHA
Antiepileptic Medication III
Third generation in phase 3 Trials (2009 – ?) Carisbamate Retigabine Eslicarbazepine Lacosamide
Nov. 09 36HHA
Vagal Nerve Stimulation
Nov. 09 37HHA
Vagal Nerve Stimulation
Nov. 09 38HHA
Questions
Nov. 09 39HHA