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  1. 1. Repetitive Transcranial Magnetic stimulation (r TMS) : New Tool , New therapy and new Hope for ADHD By : E. Abdollahian . M.D. Associate prof. of psychiatry .
  2. 2. Introduction <ul><li>ADHD is the most common developmental Dis. affecting at least 5% of school-aged children. </li></ul><ul><li>Boys are more frequently affected than girls (3/1to 4/1) </li></ul><ul><li>It persists into adulthood up to 60% of cases </li></ul><ul><li>It is characterized by : Inattention Impulsivity and Hyperactivity, that impair normal daily life function . </li></ul>
  3. 3. Introduction - count <ul><li>The long – term consequences of childhood ADHD include lower educational and vocational outcomes as well as an increase risk for antisocial behaviour & drug abuse in adulthood . </li></ul><ul><li>Environmental and genetic factors are involved in ADHD. </li></ul><ul><li>Variation in brain size and morphology are </li></ul><ul><li>present from early stages of life. </li></ul>
  4. 4. Introduction - count <ul><li>Fronto – striatum- cerebellum circuit abnormalities, mainly in the ® side considered responsible for most of the disturbed motor control and the abnormal sensory – motor program. </li></ul><ul><li>Dopamine seems to be the main neurochemical alteration underlying these morphologic alterations . </li></ul><ul><li>Stimulants are, to date, the most successful as well as the most controversial therapy for ADHD. </li></ul>
  5. 5. Neurobiological considerations in ADHD <ul><li>Smaller right- sided prefrontal regions </li></ul><ul><li>Decrease in grey matter in right frontal gyrus and right posterior cingulate gyrus </li></ul><ul><li>Asymmetry in caudate N. (Volume abnormality ) </li></ul><ul><li>Decrease in the right globus pallidus size </li></ul><ul><li>These findings support the involvement of a circuit in these areas that are certainly hypofunctional in ADHD. </li></ul>
  6. 6. Neurobiological considerations <ul><li>According to the effect of stimulant medications we should consider the dysfunction in dopaminergic transmission in frontal lobe and striatal structures. </li></ul><ul><li>Genetic studies have also reported an association between ADHD and dopaminergic dysfunction, including DA transporter as well as </li></ul><ul><li>D4 and D2 receptor gene abnormality that are found in relevant cortical, </li></ul><ul><li>basal ganglia, thalamus and has inhibitory effect. </li></ul>
  7. 7. Neuropsychological perspective of ADHD <ul><li>Attention Deficit </li></ul><ul><li>Impulsivness </li></ul><ul><li>Hyper activity functions </li></ul><ul><li>Attention deficit </li></ul><ul><li>Impulsiveness </li></ul><ul><li>Hyperactivity </li></ul>Disorder of Executive Functios Disorder of executive function
  8. 8. Locations of executive functions <ul><li>Prefrontal lobes </li></ul><ul><li>Basal ganglia structures </li></ul><ul><li>cortical area </li></ul><ul><li>Thalamus striatal area </li></ul>
  9. 9. PET , Functional MRI and Evoked potential findings: <ul><li>Atypical function of the fronto – striatal circuit in ADHD. </li></ul><ul><li>Decreased blood flow in the striatum and prefrontal regions. </li></ul><ul><li>Decrereased metabolism of frontal – cerebral in adults with ADHD </li></ul><ul><li>P300 studies have shown smaller amplitude and longer latencies which correlated with attentional dysfunction </li></ul><ul><li>Steady state visual EP strongly support right frontal dysfunction in ADHD. </li></ul>
  10. 10. Therapeutic effect of stimutants <ul><li>Bradley in 1937 started to use stimulants in the treatment of ADHD. </li></ul><ul><li>Stimulants ,in particular MPH, are the most commonly prescribed drug for ADHD and have a respons rate of 80% </li></ul><ul><li>MPH increases the striatal and frontal activation capturing DA transporter. </li></ul><ul><li>There is no doubt of efficacy and safety in short trem treatment with stimulants but some questions remain unanswered in long trem plans. </li></ul>
  11. 11. Transeranial Maguetic Stimulution (TMS) <ul><li>Is a newly developed tool for assessing functionality of the CNS. </li></ul><ul><li>Baker et al . Demonstrated its value in humans in 1985. </li></ul>
  12. 12. Transeranial Maguetic Stimulution (TMS) <ul><li>It is useful in detecting clinical and sub clinical abnormalities in many neurologic and psychiatric disorders including ADHD. </li></ul><ul><li>TMS seems to be an ideal method for studying the maturational process of motor pathways since it clearly excites the corticomotoneuronal system perseumed to be involved in ADHD. </li></ul>
  13. 13. TMS, count <ul><li>TMS findings demonstrated a delay in the maturation of the corticomotoneuronal system in Pts with ADHD (Ucles et all). </li></ul><ul><li>Moll et al, reported that children with ADHD has significantly reduced intracortical inhibition (lCl) with normal intracortical facilitation compared to normal controls. </li></ul>
  14. 14. TMS,count <ul><li>This abnormality showed improvement after giving 10 mg of MPH. </li></ul><ul><li>However most of the morphophysioneuro chemical hallmarks of ADHD involving prefrontal- caudate- cerebellar pathways with noteworthy Dopaminergic abnormalities have not yet been taken into account . Therefore it may be consider that they should be the current focus if rTMS is to be employed as a therapeutic option. </li></ul>
  15. 15. TMS, count <ul><li>rTMS has been found effective in Parkinson , Depression , OCD, Tourette’s syn. and some types of tic. </li></ul><ul><li>In children, has been tried in progressive myoclonic Epilepsy ,BMD, MDD and schizophrenia with some promising, albeit, short –term positive results. </li></ul>
  16. 16. TMS,Count <ul><li>It is now clear that rTMS at low frequencies could cause long- trem depression of cortico – cortical transmission in normal controls , as well as improvement of symptoms of some neuropsychiatric disorders commented on above , including the modulation of several neurotransmitters such as DA mainly after prefrontal cortex stimulation. </li></ul>
  17. 17. TMS, Count <ul><li>It should be noted that modulation of DA release could be due to GABAergic & glutamergic cortico striatal projection. </li></ul><ul><li>The recent reduced ICI found in ADHD Pts is known to be modulated by GABAergic synapses suggesting that a cortical instability in the excitatory and inhibitory signal exchange is present in this disorder. </li></ul>
  18. 18. TMS, Count <ul><li>Such cortical instability, with an imbalance between the so-called direct and indirect cortical pathways mediating sensory – motor integration might be the most important target for applying the appropriate rTMS treatment in ADHD. </li></ul>
  19. 19. TMS, count <ul><li>Strafella et al . Showed that rTMS applied to the left mid-dorsolateral prefrontal cortex (MDL-PFC) induced the release of endogenous dopamine from the left Caudate N. as a consequence of direct cortico-striatal axon stimulation, increasing the extracellular DA concentration. </li></ul>
  20. 20. TMS, count <ul><li>These effects making it possible to suggest that a similar mechanism leading to improvement of clinical symptoms might be considered in ADHD after applying rTMS. </li></ul>
  21. 21. TMS, count <ul><li>The fact that in depressed Pts some form of rTMS also produces similar effects to those described with the use of antidepressants , adds strength to the concepts expressed above and encourage us to apply it to ADHD Pts. </li></ul>
  22. 22. rTMS in ADHD count . <ul><li>Mally et al. concede that rTMS can produce not only a release of amins , but also an increase in the production of growth or other trophic factors. </li></ul><ul><li>Even a release of nitric oxide due to blood flow changes produced by rTMS may happen. </li></ul><ul><li>The action of these co-factors could also play a role in leading to expected clinical benefits of applying rTMS. </li></ul>
  23. 23. Conclusion <ul><li>Since the available evidence suggests this is a safe and well-tolerated technique for children, rTMS application on ADHD worth trying </li></ul><ul><li>Carefully conducted clinical trials, and systematic evidence based studies may lead us to the results on which we could strongly recommend this tool to apply for every child with ADHD symptoms. </li></ul>