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LA SAPIENZA UNIVERSITYLA SAPIENZA UNIVERSITY
Clinical Neurophysiology of Pain
G. CRUCCU, G.D. IANNETTI, A. TRUINI
EFNS Panel Neuropathic Pain, Vienna
Dept. Neurological Sciences, Rome
Clinical Neurophysiology of Pain
G. CRUCCU, G.D. IANNETTI, A. TRUINI
EFNS Panel Neuropathic Pain, Vienna
Dept. Neurological Sciences, Rome
1. Scales and Questionnaires1. Scales and Questionnaires
3. QST (quantitative sensory testing)3. QST (quantitative sensory testing)
4. Neurophysiological Methods4. Neurophysiological Methods
5. Functional Neuroimaging5. Functional Neuroimaging
2. Clinical Examination2. Clinical Examination
6. Biopsy6. Biopsy
EFNS Guidelines on Pain EFNS Guidelines on Pain Assessment (2004)Assessment (2004)
Standard electrodiagnosticsStandard electrodiagnostics
Standard neurophysiological tests (NCS, SEP)• are useful to demonstrate, quantify and localise a lesion along the sensory pathways • cannot assess small-fibre funcion
Standard neurophysiological tests (NCS, SEP)• are useful to demonstrate, quantify and localise a lesion along the sensory pathways • cannot assess small-fibre funcion
NCS SEP
Serra Marchettini
Ochoa
1998
Torebjoerk & Ochoa l990
Microneurography
Although it has provided important pathophysiological information, microneurography is time consuming and difficult, requiring both an expert investigator and a collaborative patient; hence it is unsuitable for clinical applications (Good Practice Point)
the R1 Blink Reflex and the SP1 Masseter Inhibitory Reflex, although non-nociceptive, have great diagnostic value in differentiating Classical from Symptomatic Trigeminal Neuralgia (level A evidence).
(Cruccu et al, (Cruccu et al, Neurology Neurology 2006)2006)
Blink Reflex: Aβ
Masseter Inhibitory Reflex: Aβ
Trigeminal Reflexes
Trigeminal Trigeminal Reflexes in Pain Reflexes in Pain
associated to associated to Multiple Sclerosis Multiple Sclerosis
(Cruccu et al, (Cruccu et al, Pain Pain 2009)2009)
On
se
t A
ge
Bila
tera
l
Un
ila
tera
l
Se
ns
ory
de
fic
it
No
rma
l s
en
sit
ivit
y
Ab
no
rma
l T
R
No
rma
l T
R
0
25
50
75
100 CTN
STN
**
* * **
no
rma
lize
d f
req
ue
nc
y (
%)
or
on
se
t a
ge
(y
ea
rs)
Response to treatment and involvement of first trigeminal division are similar in the two populations. Onset age is lower in CTN than STN (P <0.0001). Bilateral neuralgia and sensory deficits only occur in STN (P <0.001). Trigeminal reflexes (TR) are abnormal in STN (87%) and normal in CTN (94%) (P <0.0001). Data from 10 trials (Class I-III) in 628 patients.
Differential Differential diagnosis diagnosis
between CTN between CTN and STNand STN
(from the AAN-(from the AAN-EFNS guidelines on EFNS guidelines on
trigeminal trigeminal neuralgia 2008)neuralgia 2008)
Cutaneous Silent Period
(Truini et al Muscle Nerve 2008)
CSP LEP
Nociceptive Reflexes
Nociceptive reflexes, such as the RIII flexion reflex, the cutanous silent period and the corneal reflex, have little diagnostic value (grade C statement).
But the RIII flexion reflex appears to be the most reliable tool in assessing treatment effects (grade B recommendation).
(Garcia-Larrea et al, (Garcia-Larrea et al, Arch Med ResArch Med Res 2000) 2000)
Lower limbRIII flexion
reflex
Laser Evoked Potentials (LEPs)Laser Evoked Potentials (LEPs)
Laser stimulators raise very quickly the temperature Laser stimulators raise very quickly the temperature in the in the superficial layers of the skin, superficial layers of the skin, selectively excite free nerve selectively excite free nerve endings (mostly Aendings (mostly A and C nociceptors) and provide a and C nociceptors) and provide a synchronous afferent volley that is easily recorded from the synchronous afferent volley that is easily recorded from the scalp (over 200 studies have been published, including several scalp (over 200 studies have been published, including several top Class)top Class)
Signals and generators
Garcia-Larrea et al 2003 Truini et al 2003
LEPs in central neuropathic pain and nonorganic pain
Garcia-Larrea et al Brain 2002
In central neuropathic pain (spinal, brainstem, thalamo-In central neuropathic pain (spinal, brainstem, thalamo-cortical) LEPs are suppressed after stimulation of the cortical) LEPs are suppressed after stimulation of the painful territory, even if the laser pulses evoke painful territory, even if the laser pulses evoke hyperalgesia, and may distinguish neuropathic from non-hyperalgesia, and may distinguish neuropathic from non-organic painorganic pain
Spinal pathway conduction of A and C inputs
(Iannetti et al (Iannetti et al J NeurophysiolJ Neurophysiol. 2003). 2003)
Trigeminal Trigeminal C-LEPsC-LEPs
(Cruccu et al, (Cruccu et al, Brain Brain 2003)2003)
Because of the short conduction distance and a high receptor density, the trigeminal territory is even more advantageous for eliciting (with low-intensity large-spot pulses) “ultralate” LEPs (N2 latency about 280 ms), mediated by unmyelinated C afferents (conduction velocity 1.2 m/s).
highest density of C receptors
Trigeminal C LEPsTrigeminal C LEPs
(Cruccu et al, (Cruccu et al, Brain Brain 2003)2003)
Patients with trigeminal neuropathy:
axonal loss of all myelinated fibre groups
unmyelinated fibres spared Aδ-LEPs absent C-LEPs normal
C-LEPs in patients:Trigeminal Laser evoked potentials in
Wallenberg syndrome
(Cruccu et al (Cruccu et al BrainBrain 2003) 2003)
General results of
LEP studies in
peripheral neuropathic
pain
Truini et al NSL 2004
LEP abnormalities (%) Disease
normal delay absence n LEP
type References
73 21 6 52 T 1Agostino et al 2000
[1] Diabetic
neuropathy 38 2 60 45 H-F
2Agostino et al 2000
[3]
Postherpetic neuralgia
35 0 65 40 V 2Truini et al 2003 [20]
Small fibre neuropathy
0 30 70 10 H-F 2Truini et al 2004 [21]
Essential trigeminal neuralgia
49 35 16 47 T 1Cruccu et al 2001 [10]
Symptomatic trigeminal neuralgia
0 64 36 20 T 1Cruccu et al 2001 [10]
13 50 37 30 H-F Kakigi et al 1992 [13]
Various neuropathies
60 0 40 5 H-F 3Signle case reports
total abnormality frequency
68 % 251 all
Specificity/Sensitivity of LEPs vs. SEPs
(Garcia-Larrea and Cruccu, in preparation)(Garcia-Larrea and Cruccu, in preparation)Data from 28 studies in 441 patients
Pain in Carpal Tunnel Syndrome
(Truini et al, (Truini et al, Pain Pain 2009)2009)
PHNPHN
Correl. Correl. Pain vs. Pain vs. R1 R1 AA-LEP -LEP C-LEPC-LEPresponsesresponses
SignificantSignificantat least at least P<0.01P<0.01
(Truini et al Pain (Truini et al Pain 2008)2008)
LEPs assessing response to treatment
(Truini et al, (Truini et al, Eur J Pain Eur J Pain 2009)2009)
(Iannetti et al, J Physiol, 2007)(Iannetti et al, J Physiol, 2007)
CHEPs CHEPs vs. LEPsvs. LEPs
0 1 2 3 4 sec
Myelinated-fibre NeuropathyMyelinated-fibre Neuropathy
(Truini et al, Pain 2007)(Truini et al, Pain 2007)
Author Group Group Controlsyear A/n A/n A/nLefaucheur broad SF + SF spared2004 18/20 8/25Atherton broad 24/41 SN-IEFN 0/9 <0.0022007 reduced reduced corr <0.001Schestatsky narrow PD-CP PD2007 enhanced normalObermann broad TN ATN2007 delayed enhanced
Schestatsky 200914 meralgia paresthetica and 14 controlsCHEPs narrow ns ns clinical /NCS
reduced in amplitude
diff contr<0.001
IV
Obermann 19 HIV 9 controls narrow 11/19 0/9 <0.01 III2008 reduced
Chao narrow SN-CHEP SN-IEFN diff contr <0.00012008 reduced reduced corr <0.0001Devigili narrow ns ns IV2008
Truini broad 22/41 4\412008Truini 70 CTS broad y y painful hand painless <0.01 96% 29%2009 76 hands with pain and 14/48 1/27de Tommaso 34 CTS and 23 narrow ? ns III2009
Truini broad 27/41 12\412008
I
clinical /NCS
ns 100%clinical/ laborat.
Adelta LEP
Adelta LEP clinical /NCS
I
I
54%
clinical <0.005 71% 66%41 PHN Ophthalmic y yC-LEP
clinical <0.001 91%41 PHN Ophthalmic y yAdelta LEP
25 painful neuropathy and 25 controls
ns ns
41 sensory neuropathy and 9 controls
ns y
CHEPs /IENF
CHEPs /IENF
PREP /IENF y
IV
clinical /NCS
100% 59%
Adelta-LEP clinical
Class
I68%
IV
IV
clinical /NCS
clinical
58%
18 PDN and 9 controls ns ns
24 TN and 18 ATN ns nsPREP <0.05
Method Signif. Specif.
IV
90%clinicalAdelta-LEP y y <0.0002
10 painful neuropathy and 18 controls
Adelta LEP /IENF
clinical /NCS
Sensit.Ref. Standard
Patients Blind Prosp.Spectrum
45 sensory neuropathy
Evidence Table LEPsEvidence Table LEPs
Andrea Truini
Giandomenico Iannetti
Giorgio Cruccu
THANKS FOR YOUR
ATTENTION
THANKS FOR YOUR
ATTENTION