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Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

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Page 1: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Investigational basis of clinical neurophysiology

Edina Timea Varga MD, PhDDepartment of Neurology, University of Szeged

27th October 2015

Page 2: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

What is clinical neurophysiology?

Page 3: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

What is clinical neurophysiology??

Page 4: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Clinical neurophysiology• Specialty• Extension of neurology + special lab examinations• To study

central nervous system (CNS)peripheral nervous system (PNS)autonomic nervous system (ANS)

• To treatPD - Parkinson’s disease: DBS – deep brain stimulationEpilepsy: DBS/VNS – vagal nerve stimulation/operationTumors, lesions: resective surgerySpinal cord lesions, etc…

Page 5: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015
Page 6: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

EEG – electroencephalographyEP – evoked potentials:

visual/acustic/somatosensory/magnetic/cognitiveEMG - electromyographyENG/NCS – electroneurography/nerve conduction

studyRNS - repetitive nerve stimulationSleep studies: PSG – polysomnopgraphy, …Autonomic nervous system: sympathetic skin

respone test, RR-interval,…

Clinical neurophysiology

Page 7: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Page 8: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Resting potential

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Page 9: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Resting potential

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

-70 uV

axon

mem

bran

e

Page 10: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Na+/K+ pump: 3 Na+ out, while K+ in

Page 11: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Na+/K+ pump: 3 Na+ out, while K+ in

depolarisation

Page 12: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Na+/K+ pump: 3 Na+ out, while K+ in

depolarisation

Page 13: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

depolarisation

Page 14: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

depolarisation

Page 15: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

repolarisation

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Page 16: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

repolarisation

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

Page 17: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

return to resting potential

Page 18: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

return to resting potential

Page 19: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf

axon

mem

bran

e

return to resting potential

Page 20: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

axon

mem

bran

e

return to resting potential

Page 21: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

axon

mem

bran

e

return to resting potential

Page 22: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Purves et al. Life The Science of Biology IVth Edition 1995.

Action potential can be visualized on an oscilloscope

oscilloscope

mem

bran

e po

tent

ail (

mV)

Page 23: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Purves et al. Life The Science of Biology IVth Edition 1995.

Action potential can be visualized on an oscilloscope

oscilloscope

mem

bran

e po

tent

ail (

mV)

pair of electrodes

Page 24: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Purves et al. Life The Science of Biology IVth Edition 1995.

Action potential can be visualized on an oscilloscope

oscilloscope

mem

bran

e po

tent

ail (

mV)

pair of electrodes

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

Page 25: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Purves et al. Life The Science of Biology IVth Edition 1995.

Action potential can be visualized on an oscilloscope

oscilloscope

mem

bran

e po

tent

ail (

mV)

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 ↓.

Page 26: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Purves et al. Life The Science of Biology IVth Edition 1995.

Action potential can be visualized on an oscilloscope

oscilloscope

mem

bran

e po

tent

ail (

mV)

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 ↓.

Page 27: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015
Page 28: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

research daily routine

Page 29: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

A.C. 43. Scribonius Largus 1755, Charles Le Roy

Electric torpedo fish Pain relief and eliciting phosphene

1855, Duchenne de Boulogne

L’Electrisation LocaliseePascual-Leone&Wagner

Ann Rev Biomed Eng 2007; 9:527-565.

Transcranial direct current stimulation- historical background

Page 30: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Spontaneous neuronal discharge can be modulated by direct current in a polarity-dependent way

Creutzfeldt et al; Exp Neurology 1962; 5:436-452.

basic neuronal activity

anodal stimulation

cathodal stimulation

Transcranial direct current stimulation

Terzuolo&Bullock Proc NAS USA 1956; 42:687-694.

Page 31: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Cathodal stimulation hyperpolarisation of neuronal membranes decreases cortical excitability

Anodal stimulation depolarisation increased cortical excitability

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.

Transcranial direct current stimulation

The effect depends on: Current intensity Current density Stimulus duration Anatomical structures

After-effect (AE) depends on: Current intensity Stimulus duration

Page 32: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

www.google.com

M1

V1

Page 33: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

CSWS – continuous slow waves of sleep idiopathic childhood epilepsy continuous epileptiform discharges during

sleep neurocognitive decline behavioural dysfunctions epileptic seizures limited therapeutic approaches

M S-de-Boer Epilepsia 2009.

Varga et al. Epilepsy Res 2011.

Stimulator: Neuro Conn GmbH, Ilmenau, Germany

The effect of tDCS was measured on EEG, by quantifying the percentage of non-REM sleep containing spike-and-slow-waves.

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

Page 34: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

daily routine

Page 35: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

EEG - electroencephalography

Page 36: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

localisation

International 10/20 system

F – frontalP – parietalT – temporalO – occipitalC – centralFp – frontopolarz - zero (vertex): Fz, Cz, Pz)A – auricula

even number– right sideodd number– left side

www.ilae.org

Page 37: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

http://stock-clip.com/video-footage/eeg

Page 38: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Electrodes

a-b-c : superficial (Ag/AgCl)

d - clip

e – needle electrode

f –nasopharyngealis needle electrode

Fisch & Spehlmann

Page 39: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Common reference

Page 40: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Double banana

Page 41: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Normal (adult) background activity

Page 42: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Amplitude redution for eye opening

Page 43: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Hyperventilation – normal reaction (8 years)

4 Hz, ampl. 500 uV

Page 44: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Muscle artifact

Page 45: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Myoclonus (gen. spike and slow wave)

Page 46: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Myoclonus (gen. spike and slow wave)

Page 47: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Myoclonus (gen. spike and slow wave)

Page 48: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Left temporal (interictal) slow wave and spike

Page 49: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Generalized spike and slow wave activity

IGE – idiopathic generalized epilepsy

Page 50: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Nerve conduction studies (NCS)

motor NCS

sensory NCS

http://bcs.whfreeman.com/thelifewire9ePurves et al. Life The Science of Biology IVth Edition 1995.http://chadwaterbury.comhttp://emedicine.medscape.com/article/1846028-overviewhttp://jdr.sagepub.comhttp://www.erikstalberg.com/

Page 51: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Nerve conduction studies (NCS)

motor NCS

sensory NCS

Page 52: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Nerve conduction studies (NCS)

motor NCS

sensory NCS

time (ms)

volta

ge (u

V)

Page 53: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Nerve conduction studies (NCS)

motor NCS

sensory NCS

latency

latency

duration

duration

ampl

itude

ampl

itude

Page 54: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

AIM??

Page 55: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

• axonal /demyelinating injury

• focal/genearlised

• localisation

↓amplitude=axonal loss↓condiction velocity=demyelinisation↑latency=demyelinisation

Page 56: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Carpal tunnel syndrome

Page 57: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Carpal tunnel syndrome

treatment depends on EF rate

(mild/moderate/severe)

Page 58: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Medial and lateral plantar nerve

Page 59: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

superficial electrodes sensory nerve conduction

Medial and lateral plantar nerve

Page 60: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Motor nerve conduction study

registration with needle electroderegistration with superficial electrode

Page 61: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Near nerve technique

tarsal tunnel syndrome Morton’s metatarsalgia

Page 62: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Ulnar nerve neuropathy

Page 63: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Ulnar nerve neuropathy

Near nerve technique

Page 64: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Ulnar nerve neuropathy

Near nerve technique

Localisation of operation depends on

the location of conduction block

Page 65: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Ulnar nerve neuropathy

Near nerve technique

closer to the nervehigher detectable answermore precise information

Page 67: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015
Page 69: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

AIM??

Page 70: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

neurogen/myogen lesion

acute/chronic

reinnervation

↓amplitude, ↓duration,↑polyphasy→myogenic ↑amplitude, ↑duration,↑polyphasy→neurogenic

prescence of abnormal resting activity

reinnervation potentials

Page 71: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Investigation of neuromucular junction

Indication: Myasthenia gravis Lambert-Eaton Myasthenic Syndrome

Page 72: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

• RNS - repetitive nerve stimulationsensitivity:

• Ocular MG= 50%, • Generalised MG= 75%

• Single fiber EMG:sensitivity: 95%

Stalberg, UppsalaNandedkar

Page 73: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

EVOKED POTENTIALS

• VEP – visually evoked potentials

• (S)SEP – (somato)sensory evoked potentials

• MEP – motor evoked potentials

• BAEP (alias: ABR, BERA) – brainstem auditory evoked potentials

Page 74: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

VEP - visually evoked potentials

http://tidsskriftet.no/article/3011088/en_GB

Page 75: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

SEP somatosensory evoked potentials

http://tidsskriftet.no/article/3011088/en_GB

Page 76: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

SEP somatosensory evoked potentials: median nerve

• Erb

• Cv• Fz-A1

• C4-A1• P4-A1

• C4-Fz• P4-Fz

Page 77: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

SEP somatosensory evoked potentials: median nerve

Page 78: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

SEP somatosensory evoked potentials: median nerve

missing cortical answer in an MS patient

Page 79: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

• F.pop.

• L1

• Cz-A1

• Pz-A1

• Cz-A2

• Pz-A2

• Cz-Fz

• Pz-Fz

SEP somatosensory evoked potentials: tibial nerve

Page 80: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

missing cortical answer in an MS patient

SEP somatosensory evoked potentials: tibial nerve

Page 81: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

MEP - motor evoked potentials

http://www.gettyimages.co.uk/detail/photo/woman-having-a-transcranial-magnetic-high-res-stock-photography/487737741

Page 82: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

BAEP - brainstem evoked potentials

I. wave: N. VIII.

III. wave: cochlear nucleus, oliva superior

IV-V. wave:•lemniscus lateralis- colliculus inferior

IPL – interpeak latency:I-III, III-IV.

http://www.myvmc.com/investigations/brainstem-auditory-evoked-potential-baep/

Page 83: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Clinical neurophysiology in the treatment…

Page 84: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Operative treatment of epilepsy - lesionectomy

www.desitin.no/images/Epilepticus-sic-curabitur.jpg

Page 85: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Treatment of epilepsy (e.g.)

DBS -deep brain stimulation

VNS – vagal nerve stimulation

hippocampectomy

Page 86: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

research daily routine future

Page 87: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

https://www.youtube.com/watch?v=Al5RhaJgxxU

Page 88: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

?

Page 89: Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology, University of Szeged 27th October 2015

Thank you for your attention