Investigational basis of clinical neurophysiology Edina Timea Varga MD, PhD Department of Neurology,...

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Investigational basis of clinical neurophysiology

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

27th October 2015

What is clinical neurophysiology?

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

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

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

axon

mem

bran

e

Resting potential

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

axon

mem

bran

e

Resting potential

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

-70 uV

axon

mem

bran

e

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

axon

mem

bran

e

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

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

axon

mem

bran

e

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

depolarisation

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

axon

mem

bran

e

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

depolarisation

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

axon

mem

bran

e

depolarisation

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

axon

mem

bran

e

depolarisation

repolarisation

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

axon

mem

bran

e

repolarisation

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

axon

mem

bran

e

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

axon

mem

bran

e

return to resting potential

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

axon

mem

bran

e

return to resting potential

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

axon

mem

bran

e

return to resting potential

axon

mem

bran

e

return to resting potential

axon

mem

bran

e

return to resting potential

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)

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

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

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 ↓.

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 ↓.

research daily routine

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

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.

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

www.google.com

M1

V1

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

daily routine

EEG - electroencephalography

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

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)

4 Hz, ampl. 500 uV

Muscle artifact

Myoclonus (gen. spike and slow wave)

Myoclonus (gen. spike and slow wave)

Myoclonus (gen. spike and slow wave)

Left temporal (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/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/

Nerve conduction studies (NCS)

motor NCS

sensory NCS

Nerve conduction studies (NCS)

motor NCS

sensory NCS

time (ms)

volta

ge (u

V)

Nerve conduction studies (NCS)

motor NCS

sensory NCS

latency

latency

duration

duration

ampl

itude

ampl

itude

AIM??

• axonal /demyelinating injury

• focal/genearlised

• localisation

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

Carpal tunnel syndrome

Carpal tunnel syndrome

treatment depends on EF rate

(mild/moderate/severe)

Medial and lateral plantar nerve

superficial electrodes sensory nerve conduction

Medial and lateral plantar nerve

Motor nerve conduction study

registration with needle electroderegistration with superficial 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

Localisation of operation depends on

the location of conduction block

Ulnar nerve neuropathy

Near nerve technique

closer to the nervehigher detectable answermore precise information

AIM??

neurogen/myogen lesion

acute/chronic

reinnervation

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

prescence of abnormal resting activity

reinnervation potentials

Investigation of neuromucular junction

Indication: Myasthenia gravis Lambert-Eaton Myasthenic Syndrome

• RNS - repetitive nerve stimulationsensitivity:

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

• Single fiber EMG:sensitivity: 95%

Stalberg, UppsalaNandedkar

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

• 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

SEP somatosensory evoked potentials: tibial nerve

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 lateralis- colliculus 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 (e.g.)

DBS -deep brain stimulation

VNS – vagal nerve stimulation

hippocampectomy

research daily routine future

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

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Thank you for your attention