rutin sinir iletim calismlarinin sinirlari hatice tankisi
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Rutin sinir iletim çalıșmalarının sınırları
Hatice Tankiși, Associate professor, MD, PhdNörofizyoloji Departmanı, Aarhus Üniversite Hastanesi
VII. Korkut Yaltkaya Neurofizyoloji Sempozyumu, 21-23 Aralık, 2012, Antalya, Türkiye
Rutin sinir iletim çalıșmaları Çok eski bir teknik fakat hala en sık kullanılanı
1950, DISA A/S (Denmark)Keypoint® G4 Workstation
PC-BASE EMG SİSTEMLERI
Süre/sinir iletim hızı Amplitüd Geç yanıtlar (F-dalgası, H-refleksi) Temporal dispersion İletim bloğu Aksiyon potansiyellerinin süre ve formu
Rutin sinir iletim çalıșmaları
Supramaksimal uyarı kullanılır
Kalın miyelinli lif fonksiyonunu gösterir
Maksimal yanıtın amplitüd ve süresinin ölçümü ile akson sayısı ve saltatory iletim hakkında bilgi verir
Rutin sinir iletim çalıșmaları
Demiyelinizasyon
Aksonal kayıp
Rutin sinir iletim çalıșmaları
CMAP Amplitude
Median Ulnar Peroneal Tibialis
Mea
n de
crea
se in
CM
AP
am
p. in
SD
s
-5
-4
-3
-2
-1
0
*
*
*
SNAP Amplitude
Median dig I Median dig III Ulnar Sural
Mea
n de
crea
se in
SN
AP
am
p. in
SD
s
-8
-7
-6
-5
-4
-3
-2
-1
* *
Tankisi et al, Clin Neurophsiol 2007
● Demyelin □ Axonal *p<0.05,
53 aksonal PNP
144 duyu ve 145 motor sinir
45 demyelinizan PNP
112 duyu ve 132 motor sinir
Aksonal ve demiyelinizan PNP lerde amplitüd düșüklüğü
Tankisi et al. Clin Neurophysiol, 2007
İletim hızı ve amplitüd arasındaki ilișki
BKAP süresi ve amplitüdü arasındaki ilișki
Tankisi et al. Clin Neurophysiol, 2012
BKAP süresi
Tankisi et al. Clin Neurophysiol, 2012
Axonal loss
Demyelination
Near nerve tekniği ile duyu sinir iletim çalıșmaları
Rutin sinir iletim çalıșmalarının sınırlarıRutin sinir iletim çalıșmalarının bilgi vermediğikonular: Denervasyon ve reinnervasyon, nöromuskuler
transmisyon ve kas hastalıkları Motor birim sayısı Miyelinize olmayan C-lifleri ve ince miyelinize Aδ-
lifleri (ısı ve ağrı) Aksonların uyarılabilirliği, membran
potansiyelleri ve iyon kanal fonksiyonu
Rutin sinir iletim çalıșmalarının sınırlarıRutin sinir iletim çalıșmalarının bilgi vermediğikonular: Denervasyon ve reinnervasyon, nöromuskuler
transmisyon ve kas hastalıkları Motor birim sayısı Miyelinize olmayan C-lifleri ve ince miyelinize Aδ-
lifleri (ısı ve ağrı) Aksonların uyarılabilirliği, membran
potansiyelleri ve iyon kanal fonksiyonu
Elekromiyografi Spontan aktivite MÜP analizi (niceliksel ve niteliksel) Tam kası analizi (niceliksel ve niteliksel), turns
amplitüd analizi gibi Tek lif EMG’si Makro EMG
Denervasyon
Reinnervasyon
Elekromiyografi
Rutin sinir iletim çalıșmalarının sınırlarıRutin sinir iletim çalıșmalarının bilgi vermediğikonular: Denervasyon ve reinnervasyon, nöromuskuler
transmisyon ve kas hastalıkları Motor birim sayısı Miyelinize olmayan C-lifleri ve ince miyelinize Aδ-
lifleri (ısı ve ağrı) Aksonların uyarılabilirliği, membran
potansiyelleri ve iyon kanal fonksiyonu
MUNE (Motor unit number estimation)Motor birim sayısı bir kası innerve eden ön boynuz hücreleri veya aksonlarin sayısını gösterir Direk olarak motor unit sayısını ölçebilecek bir elektrofizyolojik teknik bulunmamaktadır O yüzden MUNE metodları kullanılmaktadır Daube, 2005
MUNE, alt motor nöron kaybi derecesi ve zamansal gelișimini gösteren en uygun elektrofizyolojik testtir
MUNE, hastalıkların teșhisi, takibi ve prognozunun belirlenmesinde ve ilaç tedavilerine yanıtı değerlendirmede faydalıdır
MUNE, ortalama yüzeysel kaydedilmiș motor unit potansiyelinin (SMUP) maksimal birlesik kas aksiyon potansiyeline (CMAP) bölünmesi temeline dayanır
MUNE (Motor unit number estimation)
Değișik MUNE Metodları MUNE metodları yüzeysel MUP (SMUP) nasıl elde
edildiğine göre değișir Inkremental stimulation Multiple point stimulation (MPS) Adapted MPS (AMPS) Statistiksel metod - submaksimal BKAP deki
değișimler ölçülür Spike triggered averaging –yüzeyel elektrodlarla
kaydedilmiș ve iğne EMG si ile tetiklenmiș ortalama MUP
MUNIX (Motor unit number index) Stimulus yanıt eğrileri/CMAP scan
“Hep ya da hiç” yanıtı
Aarhus’da MUNE deneyimi ALS’de incremental stimulation MUNE ve MUNIX
(Furtula et al, 2012) Polio’da MPS-MUNE ve MUNIX (veriler
değerlendiriliyor, Jan Nielsen) ALS’de MPS-MUNE, MUNIX ve CMAP Scan (PhD
projesi, Barıș İsak) GBS ve CIDP’de MPS-MUNE, MUNIX ve CMAP
Scan (Arastırma yılı projesi, Sansuthan Paramanathan)
Üst motor neuron hastalıklarında MPS-MUNE, MUNIX ve CMAP Scan (Ece Ünlü)
GBS’de CMAP Scan (Median sinir)Sağlıklı kontrol Demyelinizan GBS
Aksonal GBS
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
1,1
1,2
1,3
4 5 6 7 8 9 10 11 12Stimulation intensiten (mA)
CMAP
am
plitu
de (m
V)
MPS = 64 Munix = 39
MPS = 48MUNIX = 21
MPS = 256 Munix = 131
0
1
2
3
4
5
6
7
8
9
0 2 4 6 8 10 12 14 16 18 20 22 24
SI (mA)
Amp
(mV)
MPS = 256 Munix = 131
Maksimum BKAP nin %5, %50 ve %95’ini olușturan Sis (S5, S50 ve S95) Absolut SI aralıkları (S95–S5)Rölatif SI aralıkları (S95–S5)/S5)Step yüzdeleri (Blok et al., 2010)
ALS’de CMAP Scan (Median sinir)ALS
Çok etkilenmiș taraf
MPS = 188,46Munix = 150
0
1
2
3
4
5
6
7
8
9
0 2 4 6 8 10 12 14 16 18 20 22 24
SI (mA)
Amp
(mV)
MPS = 256 Munix = 131 Az etkilenmiș taraf
Sağlıklı kontrol
Rutin sinir iletim çalıșmalarının sınırlarıRutin sinir iletim çalıșmalarının bilgi vermediğikonular: Denervasyon ve reinnervasyon, nöromuskuler
transmisyon ve kas hastalıkları Motor birim sayısı Miyelinize olmayan C-lifleri ve ince miyelinize Aδ-
lifleri (ısı ve ağrı) Aksonların uyarılabilirliği, membran
potansiyelleri ve iyon kanal fonksiyonu
Küçük lif fonksiyonunun belirlenmesi
Büyük boyutlu nociceptiv olmayan afferentlerin elektriksel eșiği küçük boyutlu nociceptive afferenlere göre cok daha düșüktür
Özel teknikler (deneysel bloklar gibi) ya da özel organ uyarımları (kornea, dis eti, glans gibi) kullanılmadıkça, elektriksel uyarım nociceptive sinyalleri engelleyerek büyük affarent lifleri uyarır
Lazer uyarılmıș potansiyeller (LEPs)
Nociceptive yolların fonksiyonunu inceleyen en güvenilir ve kolay elektrofizyolojik yöntem
Radiant-ısı dalgaları seçici olarak yüzeyel derideki serbest sinir uçlarını (Aδ ve C) uyarır (Cruccu and Truini, 2010)
Ana sınırlaması sadece cok az merkezde uygulanıyor olması
neodymium:yttrium–aluminum–perovskite laser (Nd:YAP)
N2-P2 (vertikal kompleks) Cingulate girusun orta parcası
(MCC) Insular ve/vaya frontal
operkulum
N1 Sekonder somatosensoriyel alan
(SII) Posterior insula Pr. SSA (SI) (küçük bileşke) Dikkat ve algılamadan N2-P2 ye
göre daha az etkilenir Bipolar montajla daha büyük
potansiyeller elde edilir
(Cruccu et al, Clin Neurophysiol 2008)
Lazer uyarılmıș potansiyeller (LEPs)
Healthy subject
Patient 1
Patient 2
Erken küçük lif nöropatilerinin teșhisi zor olabilir
Yaklașık ½-1 saat sürebilir Habituasyon problem
Multisinaptik yollar hakkında bilgi verir PNS afferent Uzun spino- talamik yollar Talamo-kortikal yollar
Lazer uyarılmıș potansiyeller (LEPs)
Contact heat-evoked potansiyeller (CHEPs)
Hâlâ klinik geçerliliği gerekmekte olan yeni bir yöntem
Lazere göre daha büyük bir alan uyarılıyor
Iannetti et al, Physiol 2006
İğne deri biopsisi Aδ ve C sinir lifleri sayısal
olarak belirlenir ve intra-epidermal sinir lifleri (IENF) yoğunluğu ölçülür
Santral ağrıda ve demyelinizan nöropatilerde kullanılamaz
Sadece çok az sayıdaki merkezde uygulanabilir
Casanova-Molla et al, Pain 2011
Kvantitativ duyu testleri ve mikronöronografi
Kvantitativ duyu testi: Kontrollü dıș uyarımlara
karșı algılamayı test eder
Nöropatik olmayan ağrı durumlarında da değișiklikler gösterir
Zaman alıcı bir yöntem
Mikronöronografi: Miyelinize olmayan afferent
ve efferent nöronal trafiği incelemede önemli bir yöntem
Rutin sinir iletim çalıșmalarının sınırlarıRutin sinir iletim çalıșmalarının bilgi vermediğikonular: Denervasyon ve reinnervasyon, nöromuskuler
transmisyon ve kas hastalıkları Motor birim sayısı Miyelinize olmayan C-lifleri ve ince miyelinize Aδ-
lifleri (ısı ve ağrı) Aksonların uyarılabilirliği, membran
potansiyelleri ve iyon kanal fonksiyonu
Periferal sinirlerin elektriksel uyarimlarla test edilmesi
(Bostock)Sinir eksitabilite çalıșmaları: Submaksimal uyarı
kullanılır Özel uyarı yanıtlarını
ölçerek:
→ Aksonların uyarılabilirliği → Membran potansiyelleri → İyon kanal fonksiyonu
Sinir iletim çalıșmaları: Supramaksimal uyarı
kullanılır Maksimal yanıta karșı
amplitüd ve süre ölçümü ile:
→ Akson sayısı → İletim hızı
Sabrınız ve ilginiz için teșekkürler
Küçük lif fonksiyonunun belirlenmesi
Büyük boyutlu nociceptiv olmayan afferentlerin elektriksel eșiği küçük boyutlu nociceptive afferenlere göre cok daha düșüktür
Özel teknikler (deneysel bloklar gibi) ya da özel organ uyarımları (kornea, dis eti, glans gibi) kullanılmadıkça, elektriksel uyarım nociceptive sinyalleri engelleyerek büyük affarent lifleri uyarır
Stimulus Response Curve/CMAP Scan
Blok et al., 2010The Sis that elicited 5%, 50%, and 95% of the maximum CMAP (S5, S50, and S95) The absolute SI range (S95–S5), The relative SI range (S95–S5)/S5)Step percentage (sum of the step sizes of all steps relative to the maximum CMAP amplitude)
Microneurography Particularly important to
investigate efferent and afferent neural traffic in unmyelinated C fibers
Recordings of efferent discharges provide direct information about neural control of autonomic effector organs including blood vessels and sweat glands
Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control
Microneurography Particularly important to
investigate efferent and afferent neural traffic in unmyelinated C fibers
Recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands
Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control
Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control.
Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion.
Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain.
Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch.
No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans
Microneurography
Microneurography Microneurography provides useful peripheral neural
information concerning autonomic, motor and sensory functions in humans.
This method is a particularly important tool to analyze directly neural mechanisms underlying autonomic functions under normal and abnormal conditions.
Sympathetic microneurography has achieved an stable position in human autonomic testing.
By using this method, the detailed neural mechanisms underlying autonomic dysfunctions often encountered in neurological diseases such as orthostatic hypotension, sleep apnea, and sweat disturbances have been elucidated in detail as well as in cardio- and renovascular impairment.
Microneurography Microneurography also provides valuable information
concerning peripheral afferent mechanisms of motor control.
This technique provides an invaluable approach to the peripheral mechanisms involved in sensory functions of various modalities by identifying objective signals traveling in sensory afferent nerves.
In the future this method may be more and more employed in combination with other parameters of clinically neurophysiological, psychological/psychophysical, and neuroradiological methods, including functional magnetic resonance imaging and positron emission tomography, as a key approach to the central mechanisms of information processing of peripheral neural signals.
DISA 1500, Digital EMG System 1976 In 1950, DISA A/S (Denmark)
introduced a three channel EMG system capable of displaying and recording waveforms from each channel.
Nicolet Viking Microprocessor controlled EMG System, 1985
PC-BASE EMG SYSTEMS: 1993
MICROPROCESSOR-CONTROLLED EMG SYSTEMS: 1982-1993 PC-BASE EMG SYSTEMS: 1993–2001 HANDHELD & WIRELESS EMG SYSTEMS: 2001-PRESENT DAY
Nicolet Viking EMG System, 1985
Routine nerve conduction studies Use supramaximal stimuli Measure large myelinated
fibre function Show functional changes in
conduction velocity which may not persist with time
Measure amplitude and latency/conduction velocity of maximal response
Assess number of axons and saltatory conduction
Correlation between SNAP amplitude and sensory CV
○ Demyelin.● Axonal❃
Correlation (p<0.05)
Median (digit I) Median (digit III)
Sural Ulnar
Decrease in CV (SD)
Decr
ease
in S
NAP
ampl
itude
(SD)
**
**
*
Tankisi et al. Clin Neurophysiol, 2007
MUNE (Motor unit number estimation)Motor unit number refers to the number of anterior horn cells or axons innervating and controlling a single muscle. Motor unit number is a critical measure in any disease involving injury or death of motor neurons or motor axons. There is no electrophysiologic technique that allows for simple direct measurement of motor unit number. By providing an accurate estimate of motor unit number, MUNE provides insight into the underlying disorder, its distribution and severity.
MUNIX and IS MUNE in control subjects and ALS patients 48 control subjects and
14 ALS patients Retest on 14 control
subjects and follow-up on 6 ALS patients
(Furtula et al, 2012 in press)
Sensitivity: MUNIX: 0.77 IS MUNE: 0,31
MUNIX and IS MUNE in controls subjects and ALS patients
Individual values of CMAP, MUNIX and IS of 6 patients at inclusion and during follow-up.
Validity of MUNIX and IS MUNE in ALS patients
(Furtula et al, 2012 in press)
CMAP amplitude and MUNIX decreased in follow-up but IS MUNE did not decrease significantly
MUNIX and IS MUNE in controls subjects and ALS patients
Conclusion: MUNIX is a useful MUNE indicator to assess
progression of LMN affection MUNIX has lower intrasubject variability than IS MUNIX has a better sensitivity than IS
MPS and MUNIX in control subjects and polio patients
8 controls and 8 patients with history of polio
MPS MUNE and MUNIX MUAP duration, peak ratio
analysis and force measurement
patient control
MPSMUN: 1,00 mps
3,02,01,00,0
MPS
MUNE
400
300
200
100
0
MPSMUN: 2,00 munix
3,02,01,00,0
MUNIX
500
400
300
200
100
0
patient control
MPS and MUNIX in control subjects and polio patients
No significant correlation was found between QEMG changes and MPS MUNE and MUNIX in m. APB MUAP Duration
20151050
MP
S M
UN
E
120
100
80
60
40
20
0
Peak-ratio (nr/sec.pr.uV)
1,0,8,6,4,20,0
MP
S M
UN
E
120
100
80
60
40
20
0
Peak-ratio (nr/sec pr. uV)
1,0,8,6,4,20,0
MU
NIX
160
140
120
100
80
60
40
20
0
MUAP Duration
20151050
MU
NIX
160
140
120
100
80
60
40
20
0
p=0,101
p=0,111p=0,056
p=0,779
MPS and MUNIX in control subjects and polio patients
Conclusion: MPS MUNE and MUNIX are not well
correlated with QEMG methods probably due to they measure different parameters
MUNE can be a supplement for QEMG
Assesment of small-fiber function Large-size, non-nociceptive afferents (i.e., those that
do not carry pain) have a lower electrical threshold than small-size, nociceptive afferents.
Unless special techniques are used, i.e., experimental blocks or stimulation of special organs (cornea, tooth pulp, glans), electrical stimuli unavoidably also excite large afferents, thus hindering nociceptive signals.
Hence standard neurophysiological responses to electrical stimuli, such as nerve conduction studies and somatosensory- evoked potentials (SEPs), can identify, locate, and quantify damage along the peripheral or central sensorypathways, but they do not assess nociceptive pathway function.
For many years researchers have tried numerous techniques for selectively activating pain afferents.
Laser evoked potentials (LEPs) The most reliable and widely
accepted diagnostic tools for assessing nociceptive pathway function are laser evoked potentials (LEPs) and skin biopsy
The currently preferred approach uses laser stimulators to deliver radiant-heat pulses that selectively excite the free nerve endings (Ad and C) in the superficial skin layers.
Consensus from over 200 studies now confirms that late laser-evoked potentials (Ad-LEPs) are nociceptive responses.
LEPs are the easiest and most reliable neurophysiological tools for assessing nociceptive pathway function and are diagnostically useful in peripheral and central neuropathic pain.
In clinical practice, their main limitation is that they are currently available in too few centres.
Ultralate LEPs (related to C-fibre activation) are technically more difficult to record, and few studies have assessed their usefulness.
Laser evoked potentials (LEPs)
Contact heat-evoked potentials (CHEPs)
A recent development that still need clinical validation
The thermode for contact heat stimulation activates a larger surface area than the laser stimulation
CHEPs may be considered a robust technique for the evaluation of patients with sensory neuropathy, whereas LEPs might be more sensitive than CHEPs to the loss of IENF
Iannetti et al, Physiol 2006
Quantitative sensory testing Analyses perception in response to external stimuli of controlled intensity Detection and pain thresholds are determined by applying stimuli to the
skin in an ascending and descending order of magnitude. Mechanical sensitivity for tactile stimuli is measured with plastic filaments
that produce graded pressures, such as the von Frey hairs, pinprick sensation with weighted needles, and vibration sensitivity with an electronic vibrameter. Thermal perception and thermal pain are measured using a thermode, or other device that operates on the thermoelectric effect. QST has been used for the early diagnosis and follow-up of small-fibre neuropathy that cannot be assessed by standard NCS, and has proved useful in the early diagnosis of diabetic neuropathy.
QST is also especially suitable for quantifying mechanical and thermal allodynia and hyperalgesia in painful neuropathic syndromes, and has been used in pharmacological trials to assess treatment efficacy on provoked pains [2].
QST abnormalities, however, cannot provide conclusive evidence of neuropathic pain, because QST shows changes also in non-neuropathic pain states, such as rheumatoid arthritis and inflammatory arthromyalgias. QST is time-consuming and thus difficult to use in clinical practice [2].
Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers.
The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands.
Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation.
This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight.
Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control.
Muscle spindle afferent information is particularly important for the control of fine precise movements.
It may also play important roles to predict behavior outcomes during learning of a motor task.
Microneurography
Correlation between CV and CMAP amplitude
Median Peroneal
Tibial Ulnar
**
*
**
Decrease in CV (SD)
Decr
ease
in C
MAP
am
plitu
de (S
D)
○ Demyelin.
● Axonal❃Correlatio
n (p<0.05)
Tankisi et al. Clin Neurophysiol, 2007
Cutaneous silent period (CSP)
CSPElectric stimulation
CSPLaser stimulation