Download - Baclofene Intratecale e Coscienza
Baclofen Intratecale e Stato Vegetativo
Marco SaragraveRiabilitazione in Assistenza Intensiva (RAI)
S Raffaele - Cassino
Conseguenze della prima osservazione
bull Su quali basi affermiamo che il recupero osservato egrave correlato allrsquoinfusione intratecale di Baclofen
bull Per quale ragione abbiamo trascurato lrsquoipotesi che il paziente possa essersi ldquosbloccatordquo da un punto di vista motorio
bull Abbiamo sviluppato una o piugrave teorie per spiegarci il fenomeno osservato
bull Abbiamo proseguito con unrsquoosservazione su una casistica piugrave ampia di soggetti
J Neurotrauma 2009 Mar 26 [Epub ahead of print]
Defining consciousness lessons from patients and modern techniquesSaragrave M Pistoia F
Istituto San Raffaele Post-Coma and Rehabilitation Care Unit Cassino Italy marcosarasanraffaeleit
The purpose of this commentary is to expound the possible role of case-reports in exploring consciousness gradations from the vegetative state and minimally conscious state to full consciousness Peer-reviewed literature has never produced so much case-series and single case reports as in this field thus resulting in a wide collection of short-reports related to clinical prognostic and speculative issues Most relevant case reports are reviewed with a view to highlight their merits and limitations in favouring the development of a case-report based knowledge covering various aspects of disorders of consciousness
Post Hoc Ergo Propter Hoc
bull Ersquo la fallacia logica piugrave ldquodiffusardquo consiste nello stabilire una relazione causale fra due eventi dal momento che si succedono nel tempo
bull Normalmente questa fallacia puograve essere esclusa quando si disponga di un gruppo sufficientemente ampio di pazienti
bull Nel caso particolare dei pazienti con SV e MCS dobbiamo tenere in considerazione la grande eterogeneitagrave particolarmente riguardo alla distribuzione delle lesioni
bull Piugrave egrave grande il numero di casi maggiore saragrave la probabilitagrave di includere soggetti non sovrapponibili
Lrsquoesempio dello ZOLPIDEM
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
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- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Conseguenze della prima osservazione
bull Su quali basi affermiamo che il recupero osservato egrave correlato allrsquoinfusione intratecale di Baclofen
bull Per quale ragione abbiamo trascurato lrsquoipotesi che il paziente possa essersi ldquosbloccatordquo da un punto di vista motorio
bull Abbiamo sviluppato una o piugrave teorie per spiegarci il fenomeno osservato
bull Abbiamo proseguito con unrsquoosservazione su una casistica piugrave ampia di soggetti
J Neurotrauma 2009 Mar 26 [Epub ahead of print]
Defining consciousness lessons from patients and modern techniquesSaragrave M Pistoia F
Istituto San Raffaele Post-Coma and Rehabilitation Care Unit Cassino Italy marcosarasanraffaeleit
The purpose of this commentary is to expound the possible role of case-reports in exploring consciousness gradations from the vegetative state and minimally conscious state to full consciousness Peer-reviewed literature has never produced so much case-series and single case reports as in this field thus resulting in a wide collection of short-reports related to clinical prognostic and speculative issues Most relevant case reports are reviewed with a view to highlight their merits and limitations in favouring the development of a case-report based knowledge covering various aspects of disorders of consciousness
Post Hoc Ergo Propter Hoc
bull Ersquo la fallacia logica piugrave ldquodiffusardquo consiste nello stabilire una relazione causale fra due eventi dal momento che si succedono nel tempo
bull Normalmente questa fallacia puograve essere esclusa quando si disponga di un gruppo sufficientemente ampio di pazienti
bull Nel caso particolare dei pazienti con SV e MCS dobbiamo tenere in considerazione la grande eterogeneitagrave particolarmente riguardo alla distribuzione delle lesioni
bull Piugrave egrave grande il numero di casi maggiore saragrave la probabilitagrave di includere soggetti non sovrapponibili
Lrsquoesempio dello ZOLPIDEM
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
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- Slide 25
- Slide 26
- Slide 27
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- Slide 29
- Slide 30
- Slide 31
-
J Neurotrauma 2009 Mar 26 [Epub ahead of print]
Defining consciousness lessons from patients and modern techniquesSaragrave M Pistoia F
Istituto San Raffaele Post-Coma and Rehabilitation Care Unit Cassino Italy marcosarasanraffaeleit
The purpose of this commentary is to expound the possible role of case-reports in exploring consciousness gradations from the vegetative state and minimally conscious state to full consciousness Peer-reviewed literature has never produced so much case-series and single case reports as in this field thus resulting in a wide collection of short-reports related to clinical prognostic and speculative issues Most relevant case reports are reviewed with a view to highlight their merits and limitations in favouring the development of a case-report based knowledge covering various aspects of disorders of consciousness
Post Hoc Ergo Propter Hoc
bull Ersquo la fallacia logica piugrave ldquodiffusardquo consiste nello stabilire una relazione causale fra due eventi dal momento che si succedono nel tempo
bull Normalmente questa fallacia puograve essere esclusa quando si disponga di un gruppo sufficientemente ampio di pazienti
bull Nel caso particolare dei pazienti con SV e MCS dobbiamo tenere in considerazione la grande eterogeneitagrave particolarmente riguardo alla distribuzione delle lesioni
bull Piugrave egrave grande il numero di casi maggiore saragrave la probabilitagrave di includere soggetti non sovrapponibili
Lrsquoesempio dello ZOLPIDEM
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
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- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Post Hoc Ergo Propter Hoc
bull Ersquo la fallacia logica piugrave ldquodiffusardquo consiste nello stabilire una relazione causale fra due eventi dal momento che si succedono nel tempo
bull Normalmente questa fallacia puograve essere esclusa quando si disponga di un gruppo sufficientemente ampio di pazienti
bull Nel caso particolare dei pazienti con SV e MCS dobbiamo tenere in considerazione la grande eterogeneitagrave particolarmente riguardo alla distribuzione delle lesioni
bull Piugrave egrave grande il numero di casi maggiore saragrave la probabilitagrave di includere soggetti non sovrapponibili
Lrsquoesempio dello ZOLPIDEM
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
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- Slide 30
- Slide 31
-
Lrsquoesempio dello ZOLPIDEM
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
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- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Saragrave M Pistoia F Mura E Onorati P Govoni S Arch Phys Med Rehabil 2009 In Press
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Durante le prime quattro settimane lrsquoincremento alla CRS-R riguardava
soprattutto lrsquoarousal come suggerito dallrsquoascesa selettiva del punteggio dela
scala proprio negli item sensibili allrsquoattivazione
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Nei mesi successivi abbiamo osservato una maggior responsivitagrave
comportamentale soprattutto nei pazienti n 1 e n 2 (con recupero di normali
contenuti di coscienza) e nel paziente n3 (con transizione verso uno stato di
coscienza minimo e successiva emergenza dallo stesso come
testimoniato dal recupero dellrsquouso funzionale dellrsquooggetto)
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
A modulation confined to spinal cord segmental activities and to neuronal centripetal outputs
reaching the cortex
A modulation of sleep-wake cycles that although present may be dysregulated and interfere with
alertness and awareness
Saragrave et al Arch Phys Med Rehabil 2009 in press
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
In our opinion these filtering systems aimed to prevent an information overload to cortex may be in some degree impaired in patients in VS gating
deficits may cause these subjects to become overloaded by sensory stimuli contributing to a
consciousness impairment also with difficulties in distinguishing the self from nonself This overload may contribute to retard the restoration within the
cortico-thalamo-cortical connections mainly responsible for consciousness recovery
Intrathecal baclofen may modulate the amount of information reaching the cortex by influencing the
GABA related gating systems within the spinal circuits
Saragrave et al Arch Phys Med Rehabil 2009 in press
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
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-
OVERLOAD
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
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- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Gate theory
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
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- Slide 17
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- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Pain 1999 AugSuppl 6S121-6
From the gate to the neuromatrix
Melzack R
Department of Psychology McGill University Montreal Quebec Canada
The awareness of the self may be influenced by perceptual stimuli normally modulated by gating
systems acting at thalamic and spinal level as suggested by Melzackrsquos theories on gating and
neuromatrix
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
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- Slide 13
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- Slide 16
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- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Gating
bull La necessitagrave che un segnale venga gestito da sequenze ldquoappropriaterdquo di nodi appartenenti ad una data rete egrave parzialmente garantita dalla capacitagrave di inibizione ldquotrasversalerdquo di ldquonodi parallelirdquo non necessariamente coinvolti in una elaborazione funzionale (in quel dato istante)
bull I sistemi a gating posseggono questa capacitagrave generale sia in modo costitutivo che inducibile
bull Un esempio egrave fornito dallrsquoattenuazione del dolore grazie ad uno stimolo tattile applicato a livello del medesimoello stesso territorio sensitivo
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
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- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Alternative mechanism
Intrathecal baclofen may favour a modulation of sleep-wake cycles that although present may be
dysregulated and interfere with alertness and awareness
Patients in PVS show preserved wake-sleep cycles However these cycles are commonly irregular as confirmed by the criteria of the
Multi-Society Task Force on PVS and by experimental evidences on atypical sleep
features in these patients
DAleo et al Ital J Neurol Sci 199415347-351 Funct Neurol 19949189-192
Isono et al Brain Inj 200216705-712
Oksenberg et al Sleep 200124703-706
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
- Slide 13
- Slide 14
- Slide 15
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- Slide 18
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- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
Low baclofen concentrations may reach the brain through cerebrospinal fluid On the bases of the
data sheet of the drug it is possible to estimate that the intrathecal administration of baclofen may give origin to brain levels in the low micromolar range
which may well activate GABAB receptors
Since PVS may be regarded as a disconnection syndrome within cortical-subcortical networks
functionally interlinking wakefulness and awareness the clinical improvement favoured by ITB may at least be partly related to its support to
an enhanced stabilization and coherence of the circadian dynamics
Saragrave et al Arch Phys Med Rehabil 2009 in press
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
- Slide 12
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- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
-
The circuitry whose activity may serve to promote coherent functioning of large populations of cortical and thalamic
neurons with respect to perception attention alertness and awareness is subserved by a proper balance of glutamate activity on NMDA AMPA and metabotropic receptors and
GABA on GABAA and GABAB receptors
Intrathecal baclofen by acting at this level may promote a greater circadian patterns stability
This action may influence the neural plasticity orientate the brain repairing action and favour a clinical improvement
Saragrave et al Arch Phys Med Rehabil 2009 in press
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- Slide 11
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-