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Optimizing Your Child's Speech Using Evidence Based Medicine

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Optimizing Your Child's Speech Using Evidence Based Medicine Optimizing Your Child's Speech NORTHERN CALIFORNIA Using Evidence Based Medicine SOUTHERN Lanier Rossignol MD FAAFP CALIFORNIA TACA National Autism Conference | October 2019 CENTRAL FLORIDA www.rossignolmedicalcenter.com | [email protected] l 321.259.7111 DISCLAIMER While Lanier Rossignol has attempted to make the information in this presentation as accurate as possible, the information is provided without any expressed or implied warranty. The purpose of this lecture is to provide information about different conditions or treatments that may affect individuals with autism and other conditions. Please be advised that Lanier Rossignol is not giving medical advice and that circumstances may dictate different treatments. All of the reviewed treatments in this lecture are considered off- label and not FDA-approved. Before beginning any treatment, please consult with your or your child’s physician. The use of every treatment in autism is “off-label” except for Risperidone and Aripiprazole for the treatment of irritability. TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 2 “Why isn’t my child talking after a year of speech & ABA therapy when my friend’s child is?” Our story TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 3 What is autism? • American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-5) provides standardized criteria to diagnose ASD. • Persistent deficits in social communication and social interaction • Restricted, repetitive patterns of behavior, interests, or activities • Diagnostic criteria on the DSM-5 is based on observation and is subjective. Diagnostic Criteria for ASD • No blood/biological tests for diagnosing autism • Autism is a spectrum disorder– some children are mildly affected; while others are severely affected. Some have ASD from birth, whereas others regress at different ages. TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 4 • A study by Soke et al. (2018) on 4-8 year old's ASD diagnosis tells with ASD found: • 95% had at least one co-occurring little about potential condition/symptom. contributing factors or • ~50% had 4 to 5 comorbid conditions causes of ASD Paradigm shift- Soke, et al., 2018 J Autism Dev Disord 48(8):2663-2676 TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 5 Selected Comorbidities Associated with Autism GASTROINTESTINAL ENDOCRINE • Feeding problems 5.1 X (Mayes et al., 2019) • Hypothyroidism (Kellman, 2011) • Constipation 4.3-45.5% (Holingue et al 2018) • Diarrhea 2.3-75.6 % (Holingue et al 2018) ALLERGIES • Inflammatory bowel disease 0.18% (Lee et. al 2018) • Food Allergies 11.3% (Xu et al., 2018) • Low Cholesterol 23% (Benachenhou, et al, 2019) • Environmental Allergies 18.7% (Xu et al., 2018) • Skin Allergies 16.8% (Xu et al., 2018) METABOLIC • Mitochondrial Dysfunction 30-50% (Rossignol & Frye, PSYCHATRIC DISORDERS 2012) • Anxiety 60-80% (Wijnhoven et. Al. 2018) • Mitochondrial Disease 5% (Rossignol & Frye, 2012) • Phobias 29.8% (van Steenel et al., 2011) • OCD 17.40% (van Steensel et al, 2011) NEUROLOGICAL • Internet Addiction 10.80% So et al., 2017) • Seizures 13-26% (Viscidi et al. 2013) • Depression 48.6% (Hudson et al., 2019) • ADHD 30-50% (Leitner, 2014) • Suicidal Ideation/Attempt (Mayes, 2013) • Dysgraphia 59% (Mayes et al., 2019) • Bipolar disorder 6-21.4% (Selten et. Al 2015) • Cerebral Folate Deficiency (Fry & Rossignol, 2012) • Catatonia 12-17% (Mazzone et. Al 2014) • Aggression 49-68% Kane & Mazurek, 2011) TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 6 ▪ Several metabolic abnormalities have been reported to contribute to or cause a potentially reversible form of autism ❖ e.g., Cerebral Folate Deficiency ▪ The goal is to rapidly screen for these abnormalities, identify them, * Important Concept * and start treating them ▪ Testing can be done by measuring certain biomarkers (laboratory tests that may identify abnormalities) ▪ ASD has a clear biological basis with features of known medical disorders (e.g., in my opinion, it is not just a psychiatric disorder) TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 7 Six developmental trajectories characterize children with autism Receiving standard therapy Fountain, et al., 2012 Pediatrics 129(5):e1112-1120 TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 8 TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 9 • Mitochondrial Dysfunction Common • Seizures Possible Causes of Speech Delay • Cerebral Folate Deficiency in ASD Based on Research/Clinical Practice TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 10 Evidence linking • ASD is characterized by oxidative stress, mitochondrial dysfunction and immune oxidative stress, dysregulation/ inflammation mitochondrial • Evidence of oxidative stress, mitochondrial dysfunction, and dysfunction, and inflammation have been found in postmortem studies of brain tissue derived from inflammation in the individual’s with ASD. brain of individuals • Interestingly the brain regions found to contain these physiological abnormalities in individuals with autism with ASD are involved in speech and auditory A SYSTEMATIC REVIEW processing, social behavior, memory, and sensory and motor coordination. • These findings suggest ASD has a clear biological basis with features of known medical disorders. Rossignol and Frye, 2014 Front Physiol 5:150 TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 11 Mitochondrial Mitochondria are the power plants (“batteries”) in every cell of our bodies. Disease/Dysfunction as The mitochondria power our hearts, brain, muscles, digestive system, etc. possible causes of with energy in the form of adenosine speech delay in ASD triphosphate (ATP). Our mitochondria use the food we eat and the air we breathe to create energy (ATP) to enable us to run/walk, focus/pay attention, read/write/learn, & speak….. Diseased/dysfunctional mitochondria can cause individuals to have multisystemic problems. TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 12 Mitochondrial Dysfunction & ASD • Mitochondrial dysfunction is the most common metabolic abnormality associated with ASD (Rossignol & Frye, 2011). • Biomarker data suggest that mitochondrial dysfunction is present in ~1/3 children with ASD. • A small controlled study has suggested that the prevalence of mitochondrial dysfunction (at least as measured in lymphocytes) in ASD may be as high as 80% (Giulivi et al., 2010) • Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN 2010 Mitochondrial dysfunction in autism. JAMA 304:2389–2396 • Rossignol DA, Frye RE 2011 Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry, Mol Psychiatry, doi:10.1038/mp.2010.136 TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 13 Acquired mitochondrial • Many individuals with disease in ASD Autism and MD do not have a specific genetic mutation to explain the MD, raising the possibility of that MD may be acquired, at least in a subgroup of children with ASD. TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 14 • Lowered glutathione concentrations • Increased free radicals (ROS) Potential causes of • Increased tumor necrosis factor(TNFα) mitochondrial • Increased nitric oxide (NO) dysfunction in autism • Glutamate (secondary) • Environmental toxicants • Abnormal calcium signaling • Propionic acid / Clostridia • Cerebral Folate Deficiency • Medications: e.g., Risperidone inhibits Complex I TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 15 Significantly lower mitochondrial complex activity found in: Brain Region-Specific • Cerebellum –Complex III & V • Frontal Cortex -Complex I Mitochondrial Electron • Temporal Cortex – Complex II, III & V Transport Chain Complexes in Children with Autism TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 16 Mitochondrial Disease/Dysfunction • Can present at any age • Consider family history • No reliable biomarkers exists • Under-diagnosed • Think of MD when 3 or more organ systems are involved without a unifying diagnosis • Some children have mitochondrial dysfunction (MtD) that does not reach the level of MD • Mitochondrial disorders can be difficult to recognize clinically because of their diverse symptoms and clinical presentations TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 17 How do I know if my child has a mitochondrial disease or Dysfunction? Symptoms & Labs TACA National Autism Conference | October 2019 www.rossignolmedicalcenter.com | [email protected] 18 Symptoms of Mitochondrial Disorders • “Any symptom in any organ at any • Migraines age” • GI Abnormalities (diarrhea, • Developmental or growth delay constipation) • Motor delay • Slow cognitive processing speed • Clumsiness
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