Tourette Syndrome Protocol

Tourette Syndrome Protocol

This Protocol is intended as information for Practitioners and should not be substituted for medical advice, diagnosis or treatment.

Pathophysiology:

  • Tourette syndrome is a neuropsychiatric disorder characterised by motor, vocal and phonic tics.[i] Symptoms usually emerge in adolescence, and their intensity and frequency typically diminish over time. Approximately two-thirds of patients will achieve significant remission, or have mild and non-impairing tics.[ii]
  • Patients with Tourette syndrome may also experience reduced executive function (i.e. cognitive impairment) or other comorbid conditions, including autism spectrum disorders (ASD),[iii] attention-hyperactivity deficit disorder (ADHD) and obsessive compulsive disorder (OCD).[iv]
  • Abnormal motor inhibition (resulting in tics) is associated with alterations in brain connectivity, including:[v]
    1. Increased signalling from the frontal gyrus (involved in information processing) and the supplementary motor area (involved in movement control);
    2. Decreased activity of the left putamen in the dorsal striatum within the basal ganglia (involved in movement regulation); and,
    3. Higher frontal gyrus and temporal gyri connectivity (involved in multisensory integration), and lower connectivity between the cerebellum (involved in motor control) and right subthalamic nucleus within the basal ganglia (controlling action selection and impulsivity).[vi]
  • Dysregulated dopaminergic activity featuring decreased dopamine 1 (D1) receptors within the dorsal striatum,[vii] paired with increased dopamine 2 (D2) receptor expression, have been linked to tic symptoms.[viii]
  • Within the pre-motor cortex (involved in movement control), elevated glutamate/gamma-aminobutyric acid (GABA) concentrations have been observed in Tourette syndrome.[ix]
  • Abnormal immune activity, including a dysregulated response to bacterial infection,[x] abnormalities within T-regulatory cells,[xi] elevated cytokines,[xii] and upregulated microglial activation in the brain, have been noted in Tourette syndrome.[xiii],[xiv].Microglial activation is linked to tissue damage,[xv] triggering neuroinflammation, which is implicated in a range of neuropsychiatric conditions.[xvi]
  • Several genetic mutations,[xvii] maternal autoimmunity and birth complications (i.e. impaired foetal growth, preterm birth, breech birth and caesarean birth)[xviii] are linked to Tourette syndrome.[xix] Antibiotic use during childhood is also associated with a higher risk of tic disorders.[xx]

Consultation Overview:

Identify Risk Factors

In Clinic Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for further guidelines:

  • Identify the patient’s condition severity using the Yale Global Tic Severity Scale (YGTSS) for both children and adults.[xxi]
  • Use the Mood and Feelings Questionnaire (MFQ) for children aged 7 to 18 years or the Depression Anxiety Stress Scales (DASS) for children 14 years and over (as well as adults); alongside the Mood and Stress Questionnaire (MSQ) to assess the patient’s mental wellbeing. If patient has been considered a suicide risk, seek immediate guidance from a Crisis Assessment and Treatment Team (CATT) or ring triple zero (000) in an emergency.
  • For children, conduct physical examination, record body mass index (BMI), height, and head circumference, to assess development.
  • Investigate comorbidities including autoimmune conditions and brain trauma, in addition to anxiety, depression, poor concentration, or other neuropsychiatric disorders.
  • Conduct the Omega-3 Index Test; a low omega-3 index is associated with increased inflammation.
  • Assess dietary intake and identify any gaps in nutritional status to determine risk of iron deficiency.
  • Assess sleep history, including onset, maintenance, regularity, quality and quantity of sleep, and environmental factors.
  • Determine if onset is sudden, acute and highly unusual following infectious symptoms (i.e. fever, sore throat, cold and flu symptoms) to evaluate risk of infection as a driver.

Pathology Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for guidelines:

  • Investigate iron (i.e. iron studies/ferritin) and vitamin D status, as insufficiency of these nutrients is linked to tic severity and Tourette syndrome.[xxii],[xxiii]
  • Investigate inflammatory markers where indicated, including erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hs-CRP).
  • If an infectious driver is suspected, screen for streptococcus infection, mycoplasma serology, viral antibodies and stealth infections. Consider using the Cunningham panel, which measures immunoglobulin G levels directed against D1 and D2 receptors, calcium-calmodulin-dependant (CaM) kinase II, and other antibodies linked to neuropsychiatric symptoms.[xxiv] Refer to General Practitioner for streptococcal throat swab, however a negative result may not necessary exclude infectious causes.
  • Consider using the cortisol awakening response (CAR) profile test to examine hypothalamic-pituitary-adrenal (HPA) axis function.

Identify Signs of Tourette Syndrome

  • Vocal and phonic tics: Characterised as either simple (e.g. clearing of throat, sniffing, grunting, sucking) or complex (e.g. repetition of short phrases and swearing).[xxv]
  • Motor tics: Can be simple (e.g. blinking, grimacing and head-jerking) or complex (e.g. gesturing).[xxvi]

Key Drivers:

  • Acute or chronic stressors: In both children and adults, the experience of acute stress has been linked to greater tic severity.[xxvii] This influences the function of the brain by stimulating higher levels of cortisol due to persistent HPA axis activation in Tourette syndrome.[xxviii] This in turn may stimulate dopamine neuron terminals, which modulate the firing rate of GABA neurons in the basal ganglia, involved in regulating movement (i.e. tics).[xxix] Further, excess cortisol also stimulates glutamate release via N-methyl-D-aspartate (NMDA) receptors,[xxx],[xxxi],[xxxii]which may contribute to imbalanced glutamate/GABA concentrations observed in Tourette syndrome.[xxxiii]
  • Autoimmune response: Tourette syndrome is associated with a 36% greater likelihood of autoimmune disease,[xxxiv] and this may contribute to the worsening of tics via increased dopaminergic neurotransmission due to elevated cytokine activity.[xxxv] This in turn may modify the differentiation of T cells in favour of autoimmune activity via the production of anti-neuronal antibodies in the central nervous system (e.g. CaM kinase II).[xxxvi] This may further be influenced by HPA dysfunction caused by chronic stress, which can perpetuate dopamine release, driving greater pro-inflammatory cytokine activity.[xxxvii]
  • Iron deficiency: Low serum ferritin (<50 ng/mL) is associated with tic severity in Tourette syndrome.[xxxviii] Iron deficiency can cause changes in neurotransmitter homeostasis, decrease myelin production, impair synaptogenesis, and lower basal ganglia activity, which is associated with reduced cognitive function and impaired psychomotor development.[xxxix]
  • Circadian rhythm/sleep disruption: Research indicates that children with Tourette syndrome are at a greater risk of sleep disorders,[xl] and sleep 1.5 hours less than healthy populations, independent of comorbidity or psychiatric medication status.[xli] Sleep deprivation is a physiological stressor often associated with increased cortisol levels[xlii] and HPA axis activation, leading to a pattern of autonomic and neuroendocrine changes that disrupt GABA/glutamate neurotransmitter balance, which also governs the sleep-wake cycle;[xliii] also implicated in Tourette syndrome.[xliv]
  • Non-coeliac gluten sensitivity (NCGS): Significant improvement in tic severity (YGTSS scores) in both adults and children was observed in a trial measuring the effects of a gluten-free diet over 12 months, with symptom scores greatly reducing by 50% (p<0.001).[xlv] Positive effects of the gluten-free (GF) diets include aiding underlying intestinal permeability of patients with NCGS; which may enable the passage of gluten peptides to the bloodstream, crossing the blood-brain barrier. As a result, this in turn may provoke inflammatory processes within the brain, thereby stimulating tic symptomology.
  • Traumatic Brain Injury (TBI): Neuropsychiatric disorders are also a common consequence of TBI, with Tourette syndrome patients at a 1.59 greater risk compared to controls, and this has been linked to a greater risk of comorbidities in tic disorders, including depression.[xlvi] Cognitive impairments are commonly observed in patients with post-TBI neuropsychiatric conditions, which are thought to result from brain injury lesions (damage to frontal lobe and the basal ganglia) or psychological distress from TBI-related disturbances.[xlvii]

Treatment Priorities:

  • Regulate HPA axis activity to reduce excessive production of glucocorticoids and resulting subsequent stimulation of dysfunctional dopamine receptor pathways and glutamate release.
  • Minimise neuroinflammation by supporting immune regulation. Manage sources of inflammation (i.e. gluten intake and intestinal permeability, or chronic infection) to reduce activation of the microglial cells in the brain.
  • Screen for, manage and monitor nutritional deficiencies (iron and vitamin D) that may exacerbate Tourette syndrome.
  • Counsel patient on proper sleep hygiene practices to support HPA axis regulation and to support healthy glutamate/GABA neurotransmitter balance.
  • Assess gluten intake and counsel on the potential benefits of a gluten-free diet to reduce tic symptoms.
  • Monitor signs and symptoms to track treatment progress using the YGTSS in both children and adults.
  • Determine functional issues associated with mood symptoms using the MFQ, DASS and MSQ questionnaires, and provide cognitive support if indicated.
  • Monitor patient’s adherence to dietary, lifestyle and supplementary recommendations using Your Guide to Stress Less patient booklet.
  • Monitor patient’s wellbeing at regular intervals and strongly advise patient to receive additional care/support from a mental health professional, including a Psychologist and/or General Practitioner. Maintain communication with Practitioner regarding treatment and patient progress.

Red Flags:

  • Additional psychiatric disorders: Psychiatric conditions also characterised by impaired motor and habit control are common comorbidities with Tourette syndrome, including OCD and ADHD,[xlviii] in addition to anxiety[xlix] and depression.[l] Use the MFQ for children aged 7 to 18 years, or the DASS for children 14 years and over (as well as adults); alongside the MSQ to assess the patient’s mental wellbeing. Consider the Conners Comprehensive Behaviour Rating Scales if ADHD is suspected. Refer patient to General Practitioner to investigate addition diagnoses. If patient has been considered a suicide risk, seek immediate guidance from a CATT or ring triple zero (000) in an emergency.
  • Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS): In patients aged between three years and puberty, with acute onset and episodic (relapsing-remitting) tics after Group A Streptococcal infection, symptoms may mimic Tourette syndrome. The effects of PANDAS may result in involuntary movements, and additional comorbidities, including urinary frequency, development regression and insomnia.[li] Screen patients for infectious markers outlined in Pathology Investigations and refer to General Practitioner for further investigation.
  • Paediatric acute-onset neuropsychiatric syndrome (PANS): Research indicates that various non-streptococcal infections, including viral gut infections[lii] and post infectious encephalitis,[liii] may trigger tic disorders. In addition to tics, patient may also demonstrate OCD-like behaviours (i.e. compulsive handwashing, symmetry issues etc.)[liv] Screen patients for infectious markers outlined in Pathology Investigations and refer to General Practitioner for further investigation.
  • Suicide: Suicide ideation is associated with depression severity.[lv] Use the MFQ for children aged 7 to 18 or the DASS for children 14 years and over (as well as adults), alongside and the MSQ to assess patient’s mental wellbeing and refer to General Practitioner/Psychologist/Psychiatrist where indicated. If patient is deemed at risk of self-harm or harm to others, seek immediate guidance from a CATT or call triple zero (000) in an emergency.

Treatment Recommendations:

Core Recommendations – For adults and children

Herbal Support for Hyper HPA and Stress

Adult dosage: Take 1 tablet three times daily or as directed.

Anxiolytic herbs that enhance GABA activity, working against glutamate-mediated excitability in the brain, which is implicated in impaired motor control in Tourette syndrome.

Mechanism of Action/Clinical Research:

  • Zizyphus has been shown to modify the GABAα receptor subunits expressional levels,[lvi] which oppose glutamate-mediated excitability in the brain, contributing to its anxiolytic effects.[lvii]
  • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[lviii]

A clinical trial involving 154 participants with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety, poor concentration, nausea, tremors, and palpitations.[lix]

  • Kudzu has demonstrated β-adrenoceptor blocking activity[lx],[lxi] similar to pharmacological beta-blockers, which are used to reduce the physical effects of anxiety and stress such as palpitations, high blood pressure, tremor and sweating.
  • Magnolia exhibits muscle relaxing effects via GABAergic mechanisms,[lxii] as well as neuroprotective properties.[lxiii],[lxiv]

Children’s Stress And Anxiety Relief

Child’s dosage: Children aged 1 to 4 years: Mix ½ metric teaspoon (1.75 g) into 50 mL of milk or juice. Children aged 5 to12 years: Mix 1 metric teaspoon (3.5 g) into 100 mL of milk or juice.

For symptoms of stress: Take once daily.

To support sleep: Take once in the afternoon and a second dose before bed.

An effective combination of passionflower, German chamomile, magnesium (Meta Mag) and alpha-casozepine enriched hydrolysed milk protein (LactiumPURE) that enhances GABA activity, working against glutamate-mediated excitability in the brain, which is implicated in impaired motor control in Tourette sydrome.

Mechanism of Action/Clinical research:

  • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[lxv]

A clinical trial involving 154 adults with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety and poor concentration.[lxvi]

  • Chamomile contains the flavonoid, apigenin, which has modulatory actions on GABAα receptors,[lxvii] responsible for its calming and anxiolytic effects.[lxviii]
  • Magnesium improves resistance to neuropsychological stressors, such as glutamate excitotoxicity, through its actions as a voltage-gated antagonist at the glutamate NMDA receptor site.[lxix] The reduction of glutamate activity has been shown to increase the actions of the GABAergic systems.[lxx]
  • Alpha-casozepine enriched hydrolysed milk protein stimulates GABAα receptors in animal models, supporting its inhibitory effects, and has also been associated with sleep promotion.[lxxi]

Meta Mag Magnesium, Taurine & Glutamine for Stress

Dosage: Add 2 level scoops (11.9 g) to 200 mL of water, twice daily.

Magnesium, taurine and glutamine to support a healthy stress response by modulating mechanisms which trigger abnormal motor inhibition, and reducing catecholamine levels, thereby minimising the effects of physical and psychological stress (caused by lack of control over movements) on the body.

Mechanism of Action/Clinical Research:

  • Magnesium improves resistance to neuropsychological stressors, such as glutamate excitotoxicity, through its actions as a voltage-gated antagonist at the glutamate NMDA receptor site.[lxxii] The reduction of glutamate activity has been shown to increase the actions of the GABA.[lxxiii]
  • Vitamin B6 is fundamental to the production of many neurotransmitters[lxxiv] and is specifically involved in the creation of histidine to histamine, tryptophan to serotonin, glutamate to GABA, and dihydroxyphenylalanine to dopamine,[lxxv] as well as the synthesis of adrenaline and noradrenaline.[lxxvi]
  • Taurine acts as an inhibitory neurotransmitter or neuromodulator, interacting with NMDA receptors to suppress glutamatergic transmission and protect against glutamate excitotoxicity.[lxxvii]
  • Zinc acts as an inhibitory neuromodulator of glutamate release, regulating NMDA receptors.[lxxviii]
  • L-Glutamine is involved in neurotransmitter synthesis and is the precursor for glutamate and GABA.[lxxix]

Gamma-Aminobutyric Acid (GABA)

Dosage: Take 250 mg to 500 mg mixed in water or juice before bed.

GABA functions as a primary inhibitory neurotransmitter in the central nervous system (CNS), reducing neuronal hyperexcitation that contributes to tic symptomology in Tourette syndrome.

Mechanism of Action/Clinical Research:

  • GABA regulates neuronal excitability via GABA receptor subunits, which are classified into three main groups (alpha, beta and gamma).[lxxx]
  • An efficient efflux transport system enhances the passage of GABA across the blood brain barrier that also acts as an efflux pump for the excitatory amino acids, glutamate and aspartate, to reduce the brain interstitial fluid concentrations.[lxxxi]

Lipids and Tocotrienols for Healthy Cell Membranes and Cognition

Dosage: Take 1 metric teaspoon (5 mL) twice daily.

Omega-3 essential fatty acids (EFAs), phospholipids and vitamin D can assist in reducing the production of inflammatory cytokines and support neurotrophic mechanisms, thereby maintaining healthy neuronal function and balancing neurotransmitter activity.

Mechanism of Action/Clinical Research:

  • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulate the production of eicosanoids, cytokines and other factors such as peroxisome proliferator-activated receptors (PPARs), which regulate the inflammatory response.[lxxxii],[lxxxiii],[lxxxiv]
  • DHA may help to support healthy brain function, cognitive development, membrane flexibility and healthy synaptic function.[lxxxv]
  • Lower levels of vitamin D have been associated with Tourette syndrome.[lxxxvi] Its protective mechanisms in the brain have been shown to suppress oxidative stress, inhibit inflammation, provide neuroprotection, down-regulate a variety of inflammatory mediators and up-regulate a wide variety of neurotrophins.[lxxxvii]

Children’s Lipid Complex for Brain Support

Dosage: Children aged 1 to 4 years: Take ½ metric teaspoon (2.5 mL) daily. Children aged 5 to12 years: Take 1 teaspoon (5 mL) daily.

A high-quality fish oil enriched in EPA, DHA, phosphatidylserine and vitamin D3 to support healthy brain development and cognition in children. These nutrients can assist in reducing the production of inflammatory cytokines and support neurotrophic mechanisms, thereby maintaining healthy neuronal function and balancing neurotransmitter activity.

Mechanism of Action/Clinical Research:

  • EPA and DHA modulate the production of eicosanoids, cytokines and other factors such as PPARs, which regulate the inflammatory response.[lxxxviii],[lxxxix],[xc]
  • DHA may help to support healthy brain function, cognitive development, membrane flexibility and healthy synaptic function.[xci]
  • Lower levels of vitamin D have been associated with Tourette syndrome.[xcii] Its protective mechanisms in brain have been shown to suppress oxidative stress, inhibit inflammation, provide neuroprotection, down-regulate a variety of inflammatory mediators and up-regulate a wide variety of neurotrophins.[xciii]

Vitamin D3 1000 IU

Dosage: Children aged 1 to 12 years: Take 1 to 3 capsules daily OR 0.25 mL to 0.75mL daily.

Adults: Take 5 capsules or 1.25 mL daily.

Vitamin D is critical to multiple roles in the immune, metabolic and nervous systems, where adequate levels are required to modulate inflammation, maintain immune homeostasis, reduce microglial activation (CNS inflammation) and protect neurotransmitter activity.[xciv]

Mechanism of Action/Clinical Research:

Lower levels of vitamin D have been associated with Tourette syndrome.[xcv] It’s protective mechanisms in the brain have been shown to suppress oxidative stress, inhibit inflammation, provide neuroprotection, down-regulate a variety of inflammatory mediators and up-regulate a wide variety of neurotrophins.[xcvi]

Bacopa/Gingko Complex

Dosage for nervous system support (adults): Take 1 tablet twice daily.

Dosage for improving memory and cognitive performance: Take two tablets twice daily.

A potent combination of herbs and nutrients to support memory, concentration and alertness, particularly during times of stress. The combined actions of the ingredients enhance and protect cognitive function, while reducing symptoms of stress and fatigue.

Mechanism of Action/Clinical Research:

  • Increases in brain GABA levels and decreases in glutamate activity from consumption of green tea, high in L-theanine, have been observed in animal studies.[xcvii]
  • Bacosides from brahmi also display antioxidant activity in the brain and have been shown to improve cognitive function in animal studies.[xcviii]
  • Anti-inflammatory activity of withania has been shown in vivo to reduce the expression of inflammatory transcription proteins including nuclear factor kappa B (NFκB) and downstream inflammatory mediators such as tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6).

Additional Considerations:

Lactobacillus paracasei LP-33® and Lactobacillus rhamnosus (LGG®) for Immune Control

Dosage: 1 capsule daily.

Clinically trialled probiotic strains to restore immune control and moderate over-active immune responses, which may be contributing to exacerbation of tic symptoms in Tourette syndrome.

Mechanism of Action/Clinical Research:

  • Lactobacillus paracasei LP-33 and Lactobacillus rhamnosus (LGG) have been shown to induce T regulatory cell production, which provides immunoregulatory support via promoting T-cell helper (Th) 1 and Th 2 cytokine balance, dampening autoimmune dysregulation as a driver of inflammation.[xcix],[c]

Children’s Dysbiosis Support

Dosage: Children aged 0 to 12 years: Take 2/3 of a metric teaspoon twice daily.

Provides a blend of Lactobacillus rhamnosus (LGG), Lactobacillus acidophilus NCFM® and Bifidobacterium animalis subsp. lactis (Bi-07) to promote microbiome diversity and function, promoting the synthesis of protective short chain fatty acids (SCFAs), which enhance the health of intestinal enterocytes, thereby reducing intestinal permeability which may exacerbate Tourette syndrome. This combination provides probiotic strains that are ideal for everyday use to enhance gut health.

Mechanism of action:

  • Lactobacillus rhamnosus (LGG) supports a healthy intestinal ecosystem due to its ability to increase populations of bifidobacteria,[ci] that have been shown to protect intestinal barrier function.
  • Lactobacillus acidophilus (NCFM) has been shown to mitigate inflammatory damage within models of intestinal permeability and gut barrier dysfunction.[cii]
  • Lactobacillus acidophilus (NCFM) and Bifidobacterium lactis Bi-07 both have efficient metabolic flexibility, and consume a wide variety of dietary fibres and prebiotic substances, therefore likely contributing to the production of SCFAs within the gastrointestinal tract.[ciii],[civ] Animal studies indicate that SCFA production may increase brain-derived neurotrophic factor (BDNF), which supports neurogenesis and increases neural function.[cv]

Supportive Programs:

The Metagenics Stress Less Program enables the Practitioner to work with patients to help moderate and manage the effects of stress. As chronic stress is considered to be an underlying driver of tic symptomology, the Stress Less Program may help patients adapt to stress-induced activation of the HPA axis and sympathetic nervous system.

The Wellness and Healthy Ageing Program combines diet, lifestyle and herbal and nutritional interventions to support optimal health, wellbeing and quality of life, while also reducing factors that contribute to psychiatric disease development including dietary sources of inflammation.

Diet and Lifestyle Recommendations:

Diet:

  • Adherence to a Mediterranean diet is associated with lower incidences of stress-associated psychological distress.[cvi]
  • The Mediterranean diet is inclusive of a high intake of fruits and vegetables, lean protein, quality essential fatty acids, and wholegrains (limiting starchy grains and vegetables).
  • The Metagenics Wellness Diet reflects the wholefood principles of the Mediterranean diet and provides a simple guide to moderate portion size and the overall balance of macronutrients.
  • To support the reduction of tic symptoms, consider a gluten-free (GF) diet.

A GF diet may take 6 to 12 months to show full benefits. Patients may experience significant withdrawal symptoms in the early stages of elimination.

Significant improvement in tic severity (YGTSS scores) in both adults and children was observed in a trial measuring the effects of a GF diet over 12 months, with symptom scores greatly reduced (50% score reduction p<0.001).[cvii]

Lifestyle:

  • Education of parents, teachers, psychologists, and school nurses regarding the nature of Tourette syndrome is essential.[cviii]
  • Cognitive behavioural therapy (CBT), termed habit-reversal treatment, is efficacious in suppressing tics. Refer patient to appropriate psychology services.[cix]
  • Physical symptoms of stress can be reduced through relaxation exercises, including activities that involve progressive muscle relaxation and breathing control (yoga, Pilates, meditation).[cx]

Phone Applications such as Headspace provide access to guided meditations, including specific sessions that concentrate on anxiety, stress, sleep and focus.

  • Exercise has been shown to reduce chronic manifestations of stress.[cxi]

The current recommendations are between 2.5 to 5 hours of moderate intensity physical activity or 1.25 to 2.5 hours of vigorous intensity physical activity, or an equivalent combination of both moderate and vigorous activities, each week.[cxii]

  • Muscle strengthening activities are recommended on at least two days each week.[cxiii] A graded approach to exercise (increasing in frequency and intensity) is recommended for individuals who are not regularly active.
  • The Beyond Blue organisation can provide information and additional support to patients affected by anxiety, depression, substance abuse and other mental health conditions.

Clinical Investigation:

Clinical Screening

Rationale

Yale Global Tic Severity Scale (YGTSS) The YGTSS is a psychological measure designed to assess the severity and frequency of symptoms of disorders such as tic disorder, Tourette syndrome, and OCD, in children and adolescents aged 6 and older.[cxiv]
Physical Examination for Children (General)

Assess the patient’s physical health, measuring and recording their weight, height, head circumference and presence of physical injuries (i.e. potential self-harm).

If abnormalities or developmental delay is identified, refer patient to paediatrician or General Practitioner for comprehensive evaluation. See Milestone Growth Charts published by The Centre for Disease control (CDC) in Additional Resources.

Conners Comprehensive Behaviour Rating Scales

ADHD Rating Scale IV

These rating scales are the only screening tools, which have been validated for the screening of ADHD in children under 6 years.[cxv] If abnormalities are identified within screening questionnaire, refer patient to paediatrician or General Practitioner for comprehensive evaluation.
Mood and Feelings Questionnaire (MFQ) A questionnaire designed to help Practitioners establish:
  • Levels of stress, anxiety and mood concerns, prioritised in relation to each other.
  • Appropriate treatment strategies based on common response patterns under stress and neurotransmitter patterns.
Depression Anxiety Stress Scales (DASS) A self-report questionnaire designed to measure the three related negative emotional states of depression, anxiety and tension/stress.
Omega-3 Index Test A validated test that measures red blood cell EPA and DHA status. An Omega-3 Index in the desirable range of 8-12% is an indicator of better overall health.

 

Pathology Testing:

  • Cortisol Awakening Response Profile (CAR)
Ideal Reference Range:
Cortisol waking: 8.0 to 18.0 nmol/L
Cortisol waking +30 min: 8.0 to 18.0 nmol/L
Cortisol waking +60 min: 8.0 to 18.0 nmol/L
Cortisol profile, Total CAR: 23.0 to 42.0 nmol/L
Rationale:
A non-invasive saliva test that serves as a reliable marker of the stress response. The CAR test measures the predictable rise and fall in cortisol within the first hour of awakening and can be used to evaluate the overall function of the HPA axis.
  • Cunningham Panel
Ideal Reference Range:
Anti-Dopamine Receptor D1: 500 – 2,000 Titre
Anti-Dopamine Receptor D2L:  2,000 – 8,000 Titre Anti-Lysoganglioside
GM1: 80.0 - 320 Titre
Anti-Tubulin: 250 – 1,000 Titre
CaM Kinase II: 53.0 - 130%
Rationale:
Research indicates that positive changes in neuropsychiatric symptoms (associated with PANS) align with improvements in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation.[cxvi]
  • Erythrocyte Sedimentation Rate (ESR)

Ideal Reference Range:

Female:

17 to 50 years: 3 to 12 mm/hr

>50 years: 5 to 20 mm/hr

Male:

17 to 50 years: 1 to 10 mm/hr

>50 years: 2 to 15 mm/hr

Rationale:

ESR is a non-specific indicator of inflammation.

  • High-sensitivity C-reactive Protein (hs-CRP)

Ideal Reference Range:

Normal value <10 mg/L

However, ideal is <1 mg/L

Rationale:

Assessment of acute phase reaction in inflammatory disorders

  • Iron Studies

Ideal Reference Range:

Serum iron: 10-30 µg/L

Plasma ferritin (6 months to 15 years): 7- 142 µg/L

Plasma ferritin (men): 30-300 µg/L

Plasma ferritin (women): 20-200 µg/L

Total iron binding capacity: 45-80 µg/L

Transferrin saturation: 20%-40%

Rationale:

Low serum ferritin (<50 ng/mL) is associated with tic severity in Tourette syndrome.[cxvii] This may be due to highly selective diets or poor eating habits.

  • Mycoplasma pneumonia serology

Ideal Reference Range:

Normal value: Antibodies not detected.

Rationale:

May be performed in an effort to determine the infectious aetiology of neurological syndromes, such as PANS. Recent infection is confirmed by a four-fold rise in titre between acute and convalescent (three weeks or more) sera. High titres can persist for more than one year and may not indicate recent infection.

  • Serum vitamin D

(25-OH D)

Ideal Reference Range:

Ideal: 100-150 nmol/L

Normal: 40-100 nmol/L

Deficient: 0-40 nmol/L

Rationale:

Lower levels of vitamin D have been associated with Tourette syndrome,[cxviii] implicating its protective mechanisms within the brain and immune system.

  • Throat Swab (bacterial culture)

Ideal Reference Range:

Normal value: Negative.

Rationale:

Absence of significant bacterial isolates makes a viral cause (e.g. influenza A) most likely.

Used to establish the diagnosis of bacterial infection with ß-haemolytic streptococci, especially Group A subtypes (Streptococcus pyogenes). May be performed in an effort to determine the infectious aetiology of neurological syndromes, such as in PANS and PANDAS.

  • Viral and bacterial antibody screening (e.g. herpes,  simplex, borrelia burgdorferi, varicella and influenza)

Ideal Reference Range:

Normal value: Antibodies not detected.

Rationale:

May be performed in an effort to determine the infectious aetiology of neurological syndromes, such as PANS and PANDAS.

Pharmaceutical Treatments:

  • Alpha-2 agonists (e.g. clonidine and guanfacine): Used for treatment of motor tics and are considered by some experts as first-line medications because of their favorable adverse effect profile. However, they are more beneficial for treatment of behavioral symptoms and are preferred for patients with predominant psychiatric disorders.[cxix]
  • Antipyschotics/Neuroleptics (e.g. haloperidol and pimozide): Dopamine-blocking agents may be used to acutely reduce the severity of tics. However, these agents carry a risk of side effects, such as acute dystonic reactions.[cxx]
  • Antiepileptics (e.g. topiramate ): May be prescribed off-label (i.e. for purpose other than epilepsy) to treat tics.[cxxi]
  • Surgical treatment with deep brain stimulation: Deep brain stimulation been shown to be effective in some patients with disabling tics that are refractory to medications.[cxxii]

*Contact Metagenics Clinical Support to ensure product recommendations are suitable for use in conjunction with pharmaceutical medications.

Additional Resources:

  • Milestone Resources based on recommendations from the World Health Organisation (WHO) and The Centre for Disease control (CDC): Growth chart resources for Practitioners to refer to and track the development of children. An in-depth checklist for Practitioners to understand what the key developmental milestones are in order to monitor child development. A parent/carer-friendly milestone checklist for parents and carers to understand what the key developmental milestones are in order to monitor child development.

References:

[i] Ferri FF. Ferri’s clinical advisor 2020. Philadelphia (USA): Elsevier/Churchill Livingstone; 2020. p. 1379-1380.

[ii] Ferri FF. Ferri’s clinical advisor 2020. Philadelphia (USA): Elsevier/Churchill Livingstone; 2020. p. 1379-1380.

[iii] Dale RC. Tics and Tourette: a clinical, pathophysiological and etiological review. Curr Opin Pediatr. 2017 Dec;29(6):665-673.0.1097/MOP.0000000000000546.

[iv] Ferri FF. Ferri’s clinical advisor 2020. Philadelphia (USA): Elsevier/Churchill Livingstone; 2020. p. 1379-1380.

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