Investigational basis of clinical
neurophysiology
Edina Timea Varga MD, PhD
Department of Neurology, University of Szeged
27th October 2015
What is clinical neurophysiology?
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What is clinical neurophysiology?
Clinical neurophysiology
• Specialty
• Extension of neurology + special lab examinations
• To study
central nervous system (CNS)
peripheral nervous system (PNS)
autonomic nervous system (ANS)
• To treat
PD - Parkinson’s disease: DBS – deep brain stimulation
Epilepsy: DBS/VNS – vagal nerve stimulation/operation
Tumors, lesions: resective surgery
Spinal cord lesions, etc…
Clinical neurophysiology
 EEG – electroencephalography
 EP – evoked potentials:
visual/acustic/somatosensory/magnetic/cognitive
 EMG - electromyography
 ENG/NCS – electroneurography/nerve
conduction study
 RNS - repetitive nerve stimulation
 Sleep studies: PSG – polysomnopgraphy, …
 Autonomic nervous system: sympathetic skin
respone test, RR-interval,…
axon membrane
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
Resting potential
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
Resting potential
-70 uV
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
Na+/K+ pump: 3 Na+ out, while K+ in
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
Na+/K+ pump: 3 Na+ out, while K+ in
axon membrane
depolarisation
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
Na+/K+ pump: 3 Na+ out, while K+ in
axon membrane
depolarisation
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
depolarisation
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
depolarisation
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
repolarisation
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
repolarisation
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
return to resting potential
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
return to resting potential
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
return to resting potential
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
axon membrane
return to resting potential
axon membrane
return to resting potential
Action potential can be
visualized on an oscilloscope
membrane potentail (mV)
oscilloscope
Purves et al. Life The Science of Biology IVth Edition 1995.
pair of electrodes
Action potential can be
visualized on an oscilloscope
membrane potentail (mV)
oscilloscope
Purves et al. Life The Science of Biology IVth Edition 1995.
pair of electrodes
Action potential can be
visualized on an oscilloscope
membrane potentail (mV)
oscilloscope
 the electrodes detect an AP as a voltage
change across the axonal membrane
 this signal is amplified and fed into the
osilloscope
 a beam of eelctrones sweeps across the
screen in a set periode of time
Purves et al. Life The Science of Biology IVth Edition 1995.
Action potential can be
visualized on an oscilloscope
membrane potentail (mV)
oscilloscope
Alternating electric charges on two plates
makes electrone beam sweep across screen
Amplified signal from axon moves electron
beam ↑&↓.
When inside on axon is +, beams move ↑.
When inside of axon is -, beam moves ↓.
Purves et al. Life The Science of Biology IVth Edition 1995.
Action potential can be
visualized on an oscilloscope
membrane potentail (mV)
oscilloscope
Alternating electric charges on two plates
makes electrone beam sweep across screen
Amplified signal from axon moves electron
beam ↑&↓.
When inside on axon is +, beams move ↑.
When inside of axon is -, beam moves ↓.
Purves et al. Life The Science of Biology IVth Edition 1995.
research
daily routine
Transcranial direct current stimulation
- historical background
A.C. 43. Scribonius Largus
Electric torpedo fish
1755, Charles Le Roy
Pain relief and eliciting
phosphene
1855, Duchenne de Boulogne
L’Electrisation Localisee
Pascual-Leone&Wagner
Ann Rev Biomed Eng 2007; 9:527-565.
Transcranial direct current stimulation
Spontaneous neuronal discharge can be modulated by direct
current in a polarity-dependent way
cathodal
stimulation
basic
neuronal
activity
anodal
stimulation
Terzuolo&Bullock
Proc NAS USA 1956; 42:687-694.
Creutzfeldt et al;
Exp Neurology 1962; 5:436-452.
Transcranial direct current stimulation
 Cathodal stimulation  hyperpolarisation of neuronal membranes 
decreases cortical excitability
 Anodal stimulation  depolarisation increased cortical excitability
The effect depends on:
Current intensity
Current density
Stimulus duration
Anatomical structures
After-effect (AE) depends on:
Current intensity
Stimulus duration
Bindman et al; Nature 1962; 196:584-585.
Priori et al; Neuroreport 1998; 9:2257-2260.
Nitsche&Paulus J Pysiol 2000; 527(3):633-639.
M1
V1
www.google.com
CSWS – continuous slow waves of sleep






Stimulator: Neuro Conn GmbH,
Ilmenau, Germany
idiopathic childhood epilepsy
continuous epileptiform discharges during
sleep
neurocognitive decline
behavioural dysfunctions
epileptic seizures
limited therapeutic approaches

The aim of the study
 to detect the possible therapeutic effect of cathodal tDCS on
the epileptiform EEG discharges (BESA)
 neuropsychological tests (if positive effect on EEG)

Materials and methods
 Subjects: CSWS patients (age>5 years) were recruited (10/4)
 tDCS:
 cathodal tDCS (1.0 mA, 20 min) over the focus
 current density: 30 µA/ cm2
 electrodes: 0,9% NaCl (35 cm2)
 control stimulation = sham stimulation
The effect of tDCS was measured on EEG, by quantifying the percentage of nonREM sleep containing spike-and-slow-waves.
M S-de-Boer Epilepsia 2009.
Varga et al. Epilepsy Res 2011.
daily routine
EEG - electroencephalography
localisation
odd number– left side
even number– right side
F – frontal
P – parietal
T – temporal
O – occipital
C – central
Fp – frontopolar
z - zero (vertex):
Fz, Cz, Pz)
A – auricula
International 10/20 system
www.ilae.org
http://stock-clip.com/video-footage/eeg
Electrodes
a-b-c : superficial
(Ag/AgCl)
d - clip
e – needle electrode
f –nasopharyngealis
needle electrode
Fisch & Spehlmann
Common reference
Double banana
Normal (adult) background activity
Amplitude redution for eye opening
Hyperventilation – normal reaction (8 years
years))
4 Hz, ampl. 500 uV
Muscle artifact
Myoclonus
(gen
gen.. spike and slow wave
wave))
Myoclonus
(gen
gen.. spike and slow wave
wave))
Myoclonus
(gen
gen.. spike and slow wave
wave))
Left temporal (interictal
interictal)) slow wave
and spike
Generalized spike and slow wave
activity
IGE – idiopathic generalized epilepsy
Nerve conduction studies (NCS)
motor NCS
sensory NCS
http://bcs.whfreeman.com/thelifewire9e
Purves et al. Life The Science of Biology IVth Edition 1995.
http://chadwaterbury.com
http://emedicine.medscape.com/article/1846028-overview
http://jdr.sagepub.com
http://www.erikstalberg.com/
Nerve conduction studies (NCS)
motor NCS
sensory NCS
voltage (uV)
Nerve conduction studies (NCS)
motor NCS
time (ms)
sensory NCS
Nerve conduction studies (NCS)
amplitude
motor NCS
latency
duration
latency
duration
amplitude
sensory NCS
AIM??
• axonal /demyelinating injury
• focal/genearlised
• localisation
↓amplitude=axonal loss
↓condiction velocity=demyelinisation
↑latency=demyelinisation
Carpal tunnel syndrome
Carpal tunnel syndrome
Medial and lateral plantar nerve
Medial and lateral plantar nerve
 superficial electrodes
 sensory nerve conduction
Motor nerve conduction study
registration with superficial electrode
registration with needle electrode
Near nerve technique
tarsal tunnel syndrome
Morton’s metatarsalgia
Ulnar nerve neuropathy
Ulnar nerve neuropathy
Near nerve technique
Ulnar nerve neuropathy
Near nerve technique
Ulnar nerve neuropathy
closer to the nerve
higher detectable answer
more precise information
Near nerve technique
EMG - electromyography
AIM??
neurogen/myogen lesion
↓amplitude, ↓duration,↑polyphasy→myogenic
↑amplitude, ↑duration,↑polyphasy→neurogenic
acute/chronic
prescence of abnormal resting activity
reinnervation
reinnervation
potentials
Investigation of neuromucular junction
Indication:
 Myasthenia gravis
 Lambert-Eaton Myasthenic Syndrome
• RNS - repetitive nerve
stimulation
sensitivity:
• Ocular MG= 50%,
• Generalised MG= 75%
• Single fiber EMG:
sensitivity: 95%
Stalberg, Uppsala
Nandedkar
EVOKED POTENTIALS
• VEP – visually evoked potentials
• (S)SEP – (somato)sensory evoked potentials
• MEP – motor evoked potentials
• BAEP (alias: ABR, BERA) – brainstem auditory
evoked potentials
VEP - visually evoked potentials
http://tidsskriftet.no/article/3011088/en_GB
SEP somatosensory evoked potentials
http://tidsskriftet.no/article/3011088/en_GB
SEP somatosensory evoked potentials: median nerve
• Erb
• Cv
• Fz-A1
• C4-A1
• P4-A1
• C4-Fz
• P4-Fz
SEP somatosensory evoked potentials: median nerve
SEP somatosensory evoked potentials: median nerve
missing cortical answer in an MS patient
SEP somatosensory evoked potentials: tibial nerve
F.pop.
L1
Cz-A1
Pz-A1
Cz-A2
Pz-A2
Cz-Fz
Pz-Fz
SEP somatosensory evoked potentials: tibial nerve
missing cortical answer in an MS patient
MEP - motor evoked potentials
http://www.gettyimages.co.uk/detail/photo/woman-having-a-transcranial-magnetic-high-res-stock-photography/487737741
BAEP - brainstem evoked potentials
I. wave: N. VIII.
III. wave: cochlear
nucleus,
oliva superior
IV-V. wave:
•lemniscus lateraliscolliculus inferior
IPL – interpeak latency:
I-III, III-IV.
http://www.myvmc.com/investigations/brainstem-auditory-evoked-potential-baep/
Clinical neurophysiology in the
treatment…
Operative treatment of
epilepsy - lesionectomy
www.desitin.no/images/Epilepticus-sic-curabitur.jpg
Treatment of epilepsy
DBS -deep brain stimulation
(e.g
e.g.)
.)
hippocampectomy
VNS – vagal nerve stimulation
research
daily routine
future
https://www.youtube.com/watch?v=Al5RhaJgxxU
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Thank you for your attention