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

2. What is clinical neurophysiology?

3. ?

4. 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…

6.  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

7. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane

8. Resting potential http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane

9. Resting potential http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf -70 uV axon membrane

10. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane Na + /K + pump: 3 Na + out, while K + in

11. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane Na + /K + pump: 3 Na + out, while K + in depolarisation

12. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane Na + /K + pump: 3 Na + out, while K + in depolarisation

13. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane depolarisation

14. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane depolarisation

15. repolarisation http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane

16. repolarisation http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane

17. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane return to resting potential

18. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane return to resting potential

19. http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf axon membrane return to resting potential

20. axon membrane return to resting potential

21. axon membrane return to resting potential

22. Purves et al. Life The Science of Biology IVth Edition 1995. Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (mV)

23. Purves et al. Life The Science of Biology IVth Edition 1995. Action potential can be visualized on an oscilloscope oscilloscope membrane potentail (mV) pair of electrodes

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

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

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

28. research daily routine

29. 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; 9:527-565. Transcranial direct current stimulation - historical background

30. 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.

31.  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

32. www.google.com M1 V1

33. 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

34. daily routine

35. EEG - electroencephalography

36. 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 www.ilae.org

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

38. Electrodes a-b-c : superficial (Ag/AgCl) d - clip e – needle electrode f –nasopharyngealis needle electrode Fisch & Spehlmann

39. Common reference

40. Double banana

41. Normal (adult) background activity

42. Amplitude redution for eye opening

43. Hyperventilation – normal reaction (8 years) 4 Hz, ampl. 500 uV

44. Muscle artifact

45. Myoclonus (gen. spike and slow wave)

48. Left temporal (interictal) slow wave and spike

49. Generalized spike and slow wave activity IGE – idiopathic generalized epilepsy

50. 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/

51. Nerve conduction studies (NCS) motor NCS sensory NCS

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

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

54. AIM??

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

56. Carpal tunnel syndrome

57. treatment depends on EF rate (mild/moderate/severe)

58. Medial and lateral plantar nerve

59.  superficial electrodes  sensory nerve conduction Medial and lateral plantar nerve

60. Motor nerve conduction study registration with needle electrode registration with superficial electrode

61. Near nerve technique tarsal tunnel syndrome Morton’s metatarsalgia

62. Ulnar nerve neuropathy

63. Near nerve technique

64. Ulnar nerve neuropathy Near nerve technique Localisation of operation depends on the location of conduction block

65. Ulnar nerve neuropathy Near nerve technique  closer to the nerve  higher detectable answer  more precise information

66. EMG - electromyography

69. AIM??

70.  neurogen/myogen lesion  acute/chronic  reinnervation ↓amplitude, ↓duration,↑polyphasy→myogenic ↑amplitude, ↑duration,↑polyphasy→neurogenic prescence of abnormal resting activity reinnervation potentials

71. Investigation of neuromucular junction Indication:  Myasthenia gravis  Lambert-Eaton Myasthenic Syndrome

72. RNS - repetitive nerve stimulation sensitivity: Ocular MG= 50%, Generalised MG= 75% Single fiber EMG: sensitivity: 95% Stalberg, Uppsala Nandedkar

73. EVOKED POTENTIALS VEP – visually evoked potentials (S)SEP – (somato)sensory evoked potentials MEP – motor evoked potentials BAEP (alias: ABR, BERA) – brainstem auditory evoked potentials

74. VEP - visually evoked potentials http://tidsskriftet.no/article/3011088/en_GB

75. SEP somatosensory evoked potentials http://tidsskriftet.no/article/3011088/en_GB

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

77. SEP somatosensory evoked potentials: median nerve

78. missing cortical answer in an MS patient

79. F.pop. L1 Cz-A1 Pz-A1 Cz-A2 Pz-A2 Cz-Fz Pz-Fz SEP somatosensory evoked potentials: tibial nerve

80. missing cortical answer in an MS patient SEP somatosensory evoked potentials: tibial nerve

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

82. 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/

83. Clinical neurophysiology in the treatment…

84. Operative treatment of epilepsy - lesionectomy www.desitin.no/images/Epilepticus-sic-curabitur.jpg

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

86. research daily routine future

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

88. ?

89. Thank you for your attention