Hjerneanatomi og -dysfunksjon ved PU, autisme og CP -nettverk, noder og angrepspunkter Bjørnar Hassel Avd for nevrohabilitering OUS bjornar.hassel@ous-hf.no
Resting state fmri viser funksjonelle nettverk med synkronisert aktivitet
Resting state fmri viser funksjonelle nettverk med synkronisert aktivitet Hyper- og hypokonnektivitet ved autisme: 539 ASD vs. 573 matchede kontroller Di Martino et al., Mol Psychiatry 2014
Bed nucleus of the stria terminalis Stria terminalis Bed nucleus of the stria terminalis
Bed nucleus of the stria terminalis Får glutamaterg input fra amygdala, efferenter til hypothalamus medierer «kronisk» angst, stressrespons, sosial angst Bed nucleus of the stria terminalis Forventningsangst: BNST, ikke amygdala, aktiveres. Straube, Neuroimage, 2007. Hypothalamus Generalisert angst: BNST og amygdala, aktiveres. Yassa et al., J Psychiatr Res, 2012.
Bed nucleus of the stria terminalis Får glutamaterg input fra amygdala, efferenter til hypothalamus medierer «kronisk» angst, stressrespons, sosial angst/ par-dannelse, Får serotonerg input fra fra raphekjerner i mesencephalon, efferenter til VTA Aktiveres av oxytocin Bed nucleus of the stria terminalis VTA BNST Raphe Hypothalamus VTA
Bed nucleus of the stria terminalis - et mål for dyp hjernestimulering? BNST VTA Bed nucleus of the stria terminalis Raphe Hypothalamus
Bed nucleus of the stria terminalis - et mål for dyp hjernestimulering? Ctx Accumb GPi Thal BNST VTA Bed nucleus of the stria terminalis Raphe Hypothalamus
Dyp hjernestimulering ved PU: Dystoni og selvskading Lesch-Nyhan syndrom: 1/400 000. X-bundet, defekt purinmetabolisme, urat. Dystoni, selvskading, PU. The authors performed bilateral chronic stimulation of the globus pallidus internus for control of dystonic movements in a 19-yearold man with LNS. Taira et al, J Neurosurg, 2003. MRI image showing the two artifacts of the limbic (anterior) and motor (posterior) leads bilaterally implanted in the GPi. Cif et al., 2007
Dyp hjernestimulering ved PU: Dystoni og selvskading Lesch-Nyhan syndrom: 1/400 000. X-bundet, defekt purinmetabolisme, urat. Dystoni, selvskading, PU. The authors performed bilateral chronic stimulation of the globus pallidus internus for control of dystonic movements in a 19-yearold man with LNS. His self-mutilating behavior unexpectedly disappeared after chronic stimulation. Taira et al, J Neurosurg, 2003. MRI image showing the two artifacts of the limbic (anterior) and motor (posterior) leads bilaterally implanted in the GPi. Cif et al., 2007
15-year-old boy with Lesch-Nyhan disease, who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. Abel et al., 2014
15-year-old boy with Lesch-Nyhan disease, who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. Abel et al., 2014
Kan selvskading være en basalgangliedysfunksjon? Pre-op Post-op Piedimonte et al., 2015
DBS ved PU: Utagering Sano et al 1970 lagde lesjon i bakre del av hypothalamus på 51 personer med «patologisk aggresjon»: EEG Changes. By electrical stimulation of this ergotropic triangle, desynchronization of the EEG and electrocorticogram was caused in the neocortex and in the limbic structures except in the hippocampus where often rhythmic theta waves were elicited. During this stimulation in the waking state, the patient stated, if he could, that he was obsessed by extreme horror.
Stimulation of the Posterior Hypothalamus for Medically Intractable Impulsive and Violent Behavior Franzini et al., 2005 The first patient was a 36-year-old male affected by a birth anoxia and a progressive mental and motor retardation with myoclonic epilepsy which started in early childhood. By the age of 16, the intellectual impairment was found to be severe ( ). His behavior was impulsive, possessive and violent. Faced with minor frustrations, he often became aggressive or self-destructive.
Stimulation of the Posterior Hypothalamus for Medically Intractable Impulsive and Violent Behavior Franzini et al., 2005 The first patient was a 36-year-old male affected by a birth anoxia and a progressive mental and motor retardation with myoclonic epilepsy which started in early childhood. By the age of 16, the intellectual impairment was found to be severe ( ). His behavior was impulsive, possessive and violent. Faced with minor frustrations, he often became aggressive or self-destructive. Two weeks after the beginning of stimulation, neuroleptic administration was withdrawn. At that time, the patient appeared significantly calmer and more cooperative. A few weeks later, he was able to stand and walk, and to interact easily with the examiners. One year later, the therapeutic effect of stimulation was still present at the same parameters (185 Hz, 1V, 60 s) without any side effects. The patient regained a normal circadian rhythm, and the problem of his disruptive activity was completely resolved.
DBS ved PU: OCD Nucl. accumbens Cortex GPi Thal Ved OCD: Lesjon av framre ben av capsula interna. DBS av framre gyrus cinguli DBS av nucl. accumbens
DBS ved PU: Muligheter ved kognitiv svikt? DBS i fornix bedrer hukommelse hos Alzheimerpasienter Laxton et al., Ann Neurol, 2010
DBS i fornix bedrer hukommelse hos Rett-mus Mecp2 +/- mus (Rett-mus) husker dårlig Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice Hao et al., Nature, 2015
DBS i fornix bedrer hukommelse hos Rett-mus, bl.a. ved å stimulere nervecelledelingen i gyrus dentatus Fornix har både efferenter og afferenter. DBS stimulerer afferenter til gyrus dentatus Hao et al., Nature, 2015
DBS i GPi ved CP: Dystoni ved metabolske sykdommer Vidailhet et al., JNNP 2013 Vidailhet et al., J Neurol Neurosurg Psychiatry 2013
DBS i GPi: Dystoni ved stasjonær CP Romito et al., Eur J Neurol, 2015 Motor outcome measured by the Burke Fahn Marsden dystonia rating scale and total electrical energy delivered. higher pre-operative dystonia severity and occurrence of spasticity were associated with poorer outcome.
DBS ved CP: Spastisitet Cerebellum (vermis ant.) påvirker muskeltonus via retikulospinale og rubrospinale baner - Lesjoner i dype cerebellare kjerner reduserer spastisitet
DBS ved CP: Spastisitet Cerebellum (vermis ant.) påvirker muskeltonus via retikulospinale og rubrospinale baner - Lesjoner i dype cerebellare kjerner reduserer spastisitet - Elektrisk aktivering av cerebellum (eller DBS av dype kjerner) reduserer spastisitet 600 CP patients. With CCS, spasticity reduction occurred in 85% (marked 25%, moderate 34%, mild 27%) and resulted in improvements in patient drooling, speech, respiration, posture, motor performance, gait, joint range of motion, and mood states. Review: Davis, Arch Med Res 2000
Konklusjoner Funksjon er knyttet til nettverk av noder. Ved å manipulere en node kan hele nettverket påvirkes Dysfunksjon ved PU, autisme, CP kan brytes ned til manipulerbare enkeltdysfunksjoner