Childhood CNS Disorders Lecture 2024 PDF

Management of CNS Disorders Week 1, Lecture 2 CNS disorders associated with childhood & adolescence Dr Trevor Bushell HW408 Learning outcomes What are the features of CNS disorders in children/adolescents? Aetiology, prevalence, symptoms of CNS disorders associated with childhood & adoles...

Management of CNS Disorders Week 1, Lecture 2 CNS disorders associated with childhood & adolescence Dr Trevor Bushell HW408 Learning outcomes What are the features of CNS disorders in children/adolescents? Aetiology, prevalence, symptoms of CNS disorders associated with childhood & adolescence Key features of pharmacological and non- pharmacological treatments The most common disorders in young people will be studied in later lectures Childhood anxiety (2% - 24% prevalence measured worldwide) Childhood depression (1% at age 11…rising to 10% in adults) Conduct Disorder/Oppositional Defiance Disorder (2% - 5%) Substance use disorders Conditions affecting children and adolescents introduced today Autism Spectrum Disorder Attention Deficit Hyperactivity Disorder Tourette’s Syndrome Obsessive Compulsive Disorder Body Dysmorphic Disorder Eating Disorders (in-patient treatment so less relevant to today’s lecture) But first, keep in mind these three features as we go through the disorders… Feature 1: does the disorder arise from brain development problems or later functional deficits? Age at presentation: Autism/Rett Syndrome ADHD Psychiatric Can you treat or even cure a ‘neurodevelopmental’ disorder where structural changes in the brain are the cause? Feature 2 Conditions of the CNS often occur as co-morbidities, or can lead to substance misuse Why? Shared neurodevelopmental deficits? Shared risk factors? Feature 3 Conditions of the CNS often require treating the mind as well as treating the brain Combination of ‘talking therapies’ such as CBT (cognitive behavioural therapy)… …and medication (if any exist for the condition) 1: Autism Spectrum Disorder (ASD) 1% of all births; more boys than girls A clear neurodevelopmental disorder (brain imaging studies). Repetitive behaviours – hand flapping/spinning Communication deficits Social interaction deficits Slow to reach baby and toddler developmental milestones in motor skills and language. Severe forms can be accompanied by language regression, seizures, and low measured IQ (in 50%). 70% have additional co-morbid conditions such as anxiety, depression, epilepsy or ADHD.  The ‘spectrum’ from mild to severe: Recent terminology changes Many of these terms are no longer used in US DSM-5 (replaced by umbrella ‘ASD’). Also, soon to be removed from ICD and therefore UK use Pathological Demand Avoidance (PDA) is newer terminology to describe features presented in many children diagnosed with ASD: resisting and avoiding everyday demands of life, mood swings, procrastinating, lacking social understanding. Ultimately, levels of support and services required for each child are the defining characteristic.  Some people with ASD have ‘islands of genius’ Those diagnosed with ASD, but normal IQ, have enhanced visual perception and a 40% increase in mathematical ability Rex Lewis–Clack has severe autism and is blind but has perfect pitch and can memorise and play back entire symphonies after hearing them once Stephen Wiltshire can draw any skyline from memory – true photographic memory Use of the term: neurodivergent  ASD treatment does not directly involve medication Support/care/management of child and family. Environment modification: efforts to increase sensory stimuli. Psychosocial intervention: communication and interaction strategies. No recommended medication for CORE autism… …except anti-psychotic [see schizophrenia lecture] Risperidone in low doses in children with severe irritability/aggression (up to 2 mg daily in children weighing up to 45 kg, and up to 3.5 mg daily in those weighing over 45kg)…. … and pharmacological treatment for co-morbidities such as ADHD/anxiety/depression/epilepsy [see upcoming lectures] 2: Attention Deficit–Hyperactivity Disorder (ADHD) aka Hyperkinetic Disorder Clustering  ADHD numbers 3-5% of children (4 x more boys than girls) have a broad diagnosis of ADHD – many do not require treatment. 2/3 have an additional diagnosis: tics, obsessive compulsive disorder, depression, substance misuse, autistic spectrum disorders and learning difficulties (NICE, 2018). Overdiagnosis? In the US diagnosis is increasing 6% every year in 12-17 age bracket. But girls may be UNDER diagnosed. However, a constant 1% prevalence has remained for the stricter ‘hyperkinetic disorder’ diagnosis. Recent increase in adult prescriptions for ADHD – reason? Like ASD, medication should not be the first step in treatment of ADHD Group treatment: coping strategies/developing control/developing social skills Cognitive Behavioural Therapy But a decision may be made by specialist to additionally prescribe: 1. Methylphenidate 2. Dexamfetamine 3. Atomoxetine Issues with side-effects, problems with medication at school, and risk of misuse of drug should all be considered  Methylphenidate (‘Ritalin’ and others) A psychostimulant [potential cognitive enhancer] Methylphenidate blocks the dopamine transporter and norepinephrine transporter, leading to increased concentrations of dopamine and norepinephrine within the synaptic cleft. Increased receptor binding - > increased neuronal activity. Schedule 2 controlled drug, not currently licensed for use in children less than 6 years old. 800% increase in prescription over last 2 decades. Boys 5x more likely to be prescribed. 90% of all ADHD prescriptions are methylphenidate. Preventing released neurotransmitter from being cleared from the synapse is a repeated theme of action of CNS drugs Synaptic concentration increased – greater stimulation of post- synaptic neuron through receptors 2015 & 2023 Cochrane Reviews cast doubt on efficacy evidence for methylphenidate – still controversial Click here to go to 2023 publication Authors claim evidence base of methylphenidate improving ADHD symptoms to be “of very low quality”. “It was possible for people in the trials to know which treatment the children were taking.” i.e., poor clinical trials practice. Authors state that 1.2% of those on methylphenidate suffer serious adverse events including: death, cardiac issues, psychosis …but an August 2018 meta-analysis is far more positive: Lancet Psychiatry 2018;5: 727–38 Published Online August 7, 2018 Recent study (2023) states methylphenidate safe up to 2 years of treatment, with no serious adverse effects observed. Lancet Psychiatry 2023; 10; 323-333 Efficacy 3: Tourette’s Syndrome (Gilles de la Tourette) Chief symptoms are ‘Tics’ which can be: vocal (sounds) – such as grunting, coughing or shouting out words physical (movements) – such as jerking of the head or jumping up and down These can be simple or complex (making a series of physical movements or speaking a long phrase) Often associated with ADHD and OCD – and runs in families. Overall, less than 0.5% of children present with TS.  Tourette’s Syndrome and non-pharmacological treatments Underlying problem may lie in the basal ganglia, which is a part of the brain that controls motor learning, executive functions/behaviours, and emotions. Habit reversal therapy – trying to identify and stop feelings/sensations that trigger a tic. Exposure with response prevention (ERP) – involves increasing exposure to the urge to tic leads to suppression of the tic response for longer. Medicating Tourette’s and associated conditions Antipsychotics/neuroleptics: Aripiprazole, sulpiride, risperidone, pimozide, olanzapine, quetiapine and haloperidol. But side-effects [see schizophrenia lecture] Pimozide has fewer, but risk of heart problems. Clonidine, work by stimulating the alpha-2 adrenergic system, which inhibits the release of noradrenaline/norepinephrine. But drowsiness/ depression/dizziness. Topimarate (Epilepsy) also used If co-morbid with ADHD, then ADHD medications were thought to exacerbate tics. But atomoxetine does not have this effect. 4: Obsessive Compulsive Disorder (OCD) An obsession is an unwanted and unpleasant thought, image or urge that repeatedly enters a person's mind, causing feelings of anxiety, disgust or unease. A compulsion is a repetitive behaviour or mental act that someone feels they need to carry out to try to temporarily relieve the unpleasant feelings brought on by the obsessive thought. 1. mild functional impairment – obsessive thinking and compulsive behaviour 3h hrs/day OCD presentation 1% of the population Fear of deliberately harming yourself or others – for example, fear you may attack someone else, even though this type of behaviour disgusts you Fear of harming yourself or others by mistake or accident – for example, fear you may set the house on fire by accidentally leaving the cooker on Fear of contamination by disease, infection or an unpleasant substance (hand-washing) Need for symmetry or orderliness – for example, you may feel the need to ensure all the labels on the tins in your cupboard face the same way 5: Body Dysmorphic Disorder (BDD) is closely related to OCD Fears about physical appearance that go beyond low self- esteem: a functional impact on life constantly compare their looks to other people's spend a long time in front of a mirror, but at other times avoid mirrors altogether spend a long time concealing what they believe is a defect feel anxious when around other people be reluctant to seek help, because they believe others will see them as vain or self-obsessed seek cosmetic surgery, which is unlikely to relieve their distress excessively diet and exercise OCD & BDD treatment/medication -Cognitive Behavioural Therapy (CBT) – e.g. Exposure with response prevention (ERP), which encourages you to face your fear and let the obsessive thoughts occur without "neutralising" them with compulsions [85% of patients show improvement] -Sertraline or Fluvoxamine should be used when an SSRI is prescribed to children and young people with OCD, except in patients with significant comorbid depression when Fluoxetine should be used, because of current regulatory requirements (only one that has a clinical trial in children). -Fluoxetine should be used when an SSRI is prescribed to children and young people with BDD. Specific Serotonin Reuptake Inhibitors SSRIs like Fluoxetine (Prozac) Are SSRIs dangerous for children? U.S. Food and Drug Administration (FDA) issued a public warning (‘Black box warning’) in October 2004: SSRIs increase risk of suicidal thoughts/attempts, particularly in immediate period after starting medication However, a later paper seems to counter this: the benefits outweigh risks 6: Eating disorders Anorexia nervosa – when a person tries to keep their weight as low as possible; for example, by starving themselves or exercising excessively. Bulimia – when a person goes through periods of binge eating and is then deliberately sick or uses laxatives to try to control their weight. Binge eating disorder (BED) – when a person feels compelled to overeat large amounts of food in a short space of time - generally adults Eating disorder treatment -Cognitive Behavioural Therapy (CBT) -Interpersonal psychotherapy -Dietary counselling Legal aspects -England: Mental Health Act 1983 and Children Act 1989 -Scotland: The Mental Health (Care and Treatment) (Scotland) Act (2003) and the Children and Young People (Scotland) Act 2014 Parents can only over-ride if the child isn’t deemed to be ‘Gillick competent’ – > ‘involuntary treatment’ = force-feeding. -Anorexia medication: caution because heart is weakened by emaciation, SSRIs often prescribed. -Bulimia: SSRIs (Fluoxetine) prescribed at generally higher doses than for depression.  Genetics of these disorders For many psychiatric disorders, modern genetics is identifying variants within genes that increase or decrease risk. We’re not at the stage of genetic diagnostics yet…..and nowhere near gene therapy (although MECP2 gene therapy for Rett syndrome in clinical trials)… …but maybe we understand the underlying pathologies better: 40% of ASD cases have an identifiable genetic/cytogenetic issue Eating Disorders have been shown to be ‘metabo-psychiatric’ disorders, not just psychiatric OCD: new risk gene, SLITRK5, may be a future drug target Tourette’s: SLITRK1 and HDC gene mutations found – note similarity to OCD ADHD risk gene FOXP2 shown to regulate dopamine levels in mouse knockout models Reinforcement of learning points Disorders stem from early brain development or later brain activity problems Co-morbidities are very common Combined cognitive and pharmacological approaches are often used Next on MoCNSD Management of CNS disorders in children & adolescents – with Dr Gazala Akram