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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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…

 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,… Clinical neurophysiology

axon membrane

Resting potential axon membrane

Resting potential uV axon membrane

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

axon membrane Na + /K + pump: 3 Na + out, while K + in depolarisation

axon membrane Na + /K + pump: 3 Na + out, while K + in depolarisation

axon membrane depolarisation

axon membrane depolarisation

repolarisation axon membrane

repolarisation axon membrane

axon membrane return to resting potential

axon membrane return to resting potential

axon membrane return to resting potential

axon membrane return to resting potential

axon membrane return to resting potential

Purves et al. Life The Science of Biology IVth Edition Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (mV)

Purves et al. Life The Science of Biology IVth Edition Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (mV) pair of electrodes

Purves et al. Life The Science of Biology IVth Edition Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (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 Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (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 Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (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 ↓.

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A.C. 43. Scribonius Largus1755, Charles Le Roy Electric torpedo fish Pain relief and eliciting phosphene 1855, Duchenne de Boulogne L’Electrisation Localisee Pascual-Leone&Wagner Ann Rev Biomed Eng 2007; 9: 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: basic neuronal activity anodal stimulation cathodal stimulation Transcranial direct current stimulation Terzuolo&Bullock Proc NAS USA 1956; 42:

 Cathodal stimulation  hyperpolarisation of neuronal membranes  decreases cortical excitability  Anodal stimulation  depolarisation  increased cortical excitability Bindman et al; Nature 1962; 196: Priori et al; Neuroreport 1998; 9: Nitsche&Paulus J Pysiol 2000; 527(3): 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

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 Varga et al. Epilepsy Res 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

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EEG - electroencephalography

localisation International 10/20 system F – frontal P – parietal T – temporal O – occipital C – central Fp – frontopolar z - zero (vertex): Fz, Cz, Pz) A – auricula even number– right side odd number– left side

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)

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 Purves et al. Life The Science of Biology IVth Edition

Nerve conduction studies (NCS) motor NCS sensory NCS

Nerve conduction studies (NCS) motor NCS sensory NCS time (ms) voltage (uV)

Nerve conduction studies (NCS) motor NCS sensory NCS latency duration amplitude

AIM??

axonal /demyelinating injury focal/genearlised localisation ↓amplitude=axonal loss ↓condiction velocity=demyelinisation ↑latency=demyelinisation

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 electrode registration with superficial electrode

Near nerve technique tarsal tunnel syndrome Morton’s metatarsalgia

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 nerve  higher detectable answer  more precise information

EMG - electromyography

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 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

SEP somatosensory evoked potentials

SEP somatosensory evoked potentials: median nerve Erb Cv Fz-A1 C4-A1 P4-A1 C4-Fz P4-Fz

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

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.

Clinical neurophysiology in the treatment…

Operative treatment of epilepsy - lesionectomy

Treatment of epilepsy (e.g.) DBS -deep brain stimulation VNS – vagal nerve stimulation hippocampectomy

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