James I. Ausman, M.D., Ph.D. Editor

1
James I. Ausman, M.D., Ph.D.Editor SURGICAL
NEUROLOGYProfessor of Neurosurgery UCLA
Clinical Consultant Navigant Consulting, Inc.,
a Healthcare Strategic Planning and Market
Research Company Chicago, Illinois Board of
Directors Somanetics Corporation Medical
Expert KMIR 6 TV
2
How should I plan for my future as a
Neurosurgeon? What should I be thinking?
3
The Future of Neurovascular Disease
4
History of Neurosurgery

• Year Science Advance
• 200 BC Craniotomy China drugs
• 1880 AD Physiology of NS Neurological
  Examination localization
• 1910s Develop Neurosurgery Surgery as Treatment
• 1920s Ventriculography Better localization
• 1930s Angiography Blood vessel
  diseaseslocalization
• 1940s Antibiotics Infections drugs for
  disease
• 1950s Radiation Therapy New Treatment of Tumors
• 1960s Chemotherapy New Treatment of tumors
  Decadron
• 1970s Microscope Micro-neurosurgery
• 1980s CT Better localization
• 1990s MR Better localization
• 2000 Image Guided Surgery
• 2005 Genetic code Molecular Medicine
• Molecular Imaging Less Surgery

5
The Future you should consider in this
Presentationwill be printed in GOLD
6
Imaging

• Molecular Imaging

7
Imaging-2010

• Major advances in MR technology will
  significantly change the practice of medicine
• High field magnets 10-20Tesla will permit
  visualization of 500 micron pixels influencing
  angiography and spectroscopy

8
Imaging-Angiography-2010

• MR/CT angiography will replace conventional
  angiography
• 10-20 tesla magnets in MR machines
• 500 micron pixel resolution

9
3 Tesla MR Angio

• 2000

10
Multidetector row CT angio in detecting spinal AV
Fistula
Lai et al. Stroke 361562-64, 2005
11
8 T MR Imaging in stroke
Novak et al. Magnetic Resonance Imaging 23,
539-48,2005
Note more detail, more lesions found, more
vessels, more pathology
12
Novak et al. Magnetic Resonance Imaging 23
539-47, 2005 B-D 8T Imaging 2 years prior to
hemorrhage in A Note Venous Angioma (D) with
feeding vessel and iron deposits around vessel A
1.5 T Flair image
13
Novak et al. Magnetic Resonance Imaging
23538-47, 2005
A,D 1.5T B,E 8T C,F 8T Phase Reversal
Note detail of vessels in 8T, anatomy
14
Current Imaging Technologies
CT
MR
15
Future of Imaging Technology
16
Image Fusion and Surgery

• Precise fusion of digital images
• CT, MR, MR Spectroscopy, Functional MR, SPECT
  others

17
(No Transcript)
18
Image Fusion and Surgery of the Future

• You will look at fused images on your computer
• You will plan surgery at home from images
• You will use the Internet to see how others in
  the world do this surgery

19
Imaging-Anatomy Fiber Tracts

• New advances in MR allow imaging of fiber tracts

20
Biological Psychiatry 55 201-207, 2004
21
(No Transcript)
22
(No Transcript)
23
Occulomotor nerves
Optic radiations
Pyramidal Tracts
Pyramidal Tracts
24
Guye, et al NeuroImage 19 1349-60, 2003
Combined functional MR and tractography (DTI) to
demonstrate connectivity in human motor cortex in
vivo
25
Combined functional MR and tractography to
demonstrate connectivity in human motor cortex in
vivo
Tumor
26
The Study of Emotions
Science 302290-92, 2003
27
The Study of Emotions

• Anterior cingulate area activated in painful or
  rejection circumstances
• Prefrontal activated to inhibit pain or distress
  (from emotional pain)
• Physical and emotional pain processed similarly
• Experiment excluded player from play causing
  distress (pain)

28
Major Changes in Psychiatry

• fMR is revealing the sites of emotion, fear, etc.
• Many diseases seen by psychiatrists now have a
  genetic explanation
• Schizophrenia, Bipolar disorders
• Obsessive compulsive behaviors
• Depression
• Fear response

29
Science 297400-402, 2002 Science 306 2023,
2004
30
Major Changes in Psychiatry

• Imaging and genetics will transform psychiatry to
  a BIOLOGICAL discipline
• Refractory depression is now being treated with
  deep brain stimulation
• Depression is being treated with vagal
  stimulation making psychiatry now collaborative
  with neurosurgery

31
Major Changes in Neurology

• Many neurological diseases are now caused by
  genetic changes
• Neurological Illnesses will undergo specific
  targeted molecular treatments in the future

32
Defects in mitochondrial fusion lead to
Charcot-Marie Tooth disease and dominant optic
atrophy. Science 305 1723-4, 2004
33
Imaging, Neurology, Neurosurgery, and Psychiatry

• The advances in imaging and genetics will make
  neurology, neurosurgery, and psychiatry closer as
  all find that they are working on the same
  biological brain which can now be understood
• Neurosurgeons will be working with Neurologists
  and Psychiatrists on many diseases
  Multidisciplinary Group Practice

34
PET Scanning Location of Drug and synapse
activity
35
Imaging-Metabolism-Spectroscopy-2010

• 10-20 Tesla magnets
• At gt20 Tesla can now visualize protein structure
  of molecules in vitro
• MOLECULAR IMAGING

36
(No Transcript)
37
(No Transcript)
38
(No Transcript)
39
(No Transcript)
40
(No Transcript)
41
Imaging MR gt10 Tesla- 2010

• Will revolutionize the practice of medicine
• Will become molecular imaging and medicine,
  neurosurgery, neurology and psychiatry
• We will be working at the molecular level for all
  diseases
• Should you become interested in Molecular Imaging
  as it applies to Neurological Disease?
• Should you be part of a MULTIDISCIPLINARY
  PRACTICE?
• Why do we practice SOLO or in small groups?

42
Cerebral Blood Flow
43
Diagnosis-2001 Cerebral Blood Flow

• Flows in cerebral vessels can be determined by
  Phase Contrast MR
• Metabolism by MR spectroscopy

44
(No Transcript)
45
(No Transcript)
46
(No Transcript)
47
Computer Simulation and Disease-2005

• Computer Simulation of the cerebral circulation
  will become routine
• Treatment options will be made for each patient,
  INDIVIDUALIZED
• selection of treatment will be OBJECTIVELY based

Neurosurgeons will work with Engineers in solving
medical problems
48
Computer Simulation and Cerebral Ischemia

• The collateral circulation will become quantified
• By blood flow distribution (XeCT)
• By simulation methodology
• Will allow better determination of risk of
  cerebral infarction
• Will be key advance in CNS vascular disease

49
Cerebral Ischemia Treatment 2015

• PREVENTION will become the key strategy for
  treatment of cerebral ischemia
• Prevention efforts will be more rewarding than
  treatment after ischemia or infarction
• Japanese Brain Dock program
• You will have a larger number of patients to see
  before they have symptoms

50
Data from Market Research

• 1 out of 3 people will have a neurological
  (including psychiatric) disease
• 50-60 Million people in Brazil
• Neurosurgeons working with other neuro-clinicians
  will have a huge number of people to treat in the
  future
• MULTIDISCIPLINARY PRACTICE

51
Molecular Biology
52
MITOTIC CHROMOSOMES
How will medicine be practiced in the 21st
century?
CHROMATIN FIBRES
Study of disorders of cell metabolism and function
NUCLEOSOMES
HISTONES
DNA
53
Molecular Biology and Cerebral Ischemia
54
1Frijns and Kappelle Stroke 33 2115-22, 2002
2Zhang et al Stroke341790-1795,
2003SEQUENCE OF EVENTS IN ISCHEMIA

• 1) Ischemic Injury
• 2) Genes Upregulated
• 3) Secondary Effects of Injury in Metabolic
  Changes
• 4) Molecular Signal molecules appear on
  endothelium
• 5) Inflammatory cellular adhesion molecules (CAM)
  attach to the endothelium and migrate between the
  cells to the interstitial space in ischemia.
• Anti CAM antibodies reduce infarct size1
• Better results with tPA 4 hrs after infarct2

55
Pleasure et al. Arch Neurol. 59 692-694 2002.

• VEGF (Vascular endothelial growth factor)
  increased with tissue hypoxia
• Genetically induced by hypoxia controlled
  transcription factor
• Improves neuronal survival , new vessel formation
• When given 48 hrs after ischemia neurological
  recovery improved

56
Shabitz et al Stroke 34 745-751, 2003

• Granulocyte colony-stimulating factor
• Genetically induced by ischemia
• Produces neuroprotective effect in stroke in
  animals

57
Moskowitz and Lo Stroke 34 324-326, 2003

• Apoptotic Cell Death
• Ischemia genetically activates capsases which
  promote cell death by cleaving repair proteins
• Inhibition of capsases reduces ischemic injury
• Capsase independent apototic pathways
• Produce AIF (apoptosis inducing factor)
• Blocked by Bcl-xL proteins

58
Molecular Biology of Ischemia

• What are the sequence of molecular events from
  genes to and from proteins in the ischemic cell?
• What interventions in the multi-step signaling
  pathway can be made to modify cell ischemia?

59

• Wang and Feuerstein in Mechanisms of Secondary
  Brain Damage From Trauma and Ischemia
• 
  Baethmann et al (eds)
  Springer-Wein New York 2004

60
(No Transcript)
61
TNF-R1 Signaling Science 296 1634-1636, 2002
62
1Warach Stroke 34 345-347, 2003

• What will be needed?
• Non invasive means of assessing biochemical
  changes needed
• Must be done many times to follow changing
  molecular chemistry
• MR, PET, MR spectroscopy1
• Minimally invasive techniques
• Microdialysis probes

63
Molecular Treatments-2010

• SOLUTION
• Patients will be treated in ICUs with imaging
  systems in units to determine changing molecular
  events
• Staged chemotherapeutic hemodynamic treatments
  based on information in each patient
• Rx apoptosis Cell and axon molecular events
  genetic events endothelial and astrocyte events
• Neuro Intensive Care will be an Important
  Specialty

64
Molecular Neurosurgery

• Similar molecular events initiated by genes will
  direct cell death or cell recovery in
• Brain Trauma
• Spinal Cord Injury
• Brain, tumors and cerebral edema
• Neurointensive Care will be a growing field

65
Cerebral Ischemia Treatment-2005

• Angioplasty and stents will be used more commonly
  for cerebral vascular stenotic disease as in the
  coronary arteries

66
(No Transcript)
67
Treatment-2005

• Stents will be used for intracranial stenoses
• New stent technology
• Biodegradable
• Impregnated to prevent restenosis
• Designed to fit vessel morphology
• Endovascular neurosurgery (interventional
  neuroradiology) will become an important
  specialty for neurosurgeons

68
Cerebral Ischemia Treatment 2010-2020

• Cerebral bypass surgery will become more commonly
  used
• Increased knowledge of cerebral vessel flows,
  metabolism
• simulation
• Will provide better selection of patients

69
Laser assisted Bypass without temporary occlusion
Tulleken et al Neurosurgery 504150420, 2002
70
(No Transcript)
71
What about the most common cause of
infarctCAPSULAR INFARCTS?
72
C.M. Fisher Capsular Infarcts The Underlying
Vascular Lesions. Arch Neurol 36 65-73, 1979
73
Capsular Infarcts Prevention

• With better imaging stenotic lesions in the
  lenticulo-striate arteries will be treated by
  STENTS
• We will need small vessel stent technology
• Endovascular Neurosurgery

74
What will happen to Atherosclerosiswhich is the
major cause of cerebral and cardiac disease?
75

• Libby, Atherosclerosis The New View, Scientific
  American, May 2002

Atherosclerosis is an Inflammatory disease

76
(No Transcript)
77
Atherosclerosis is an inflammatory disease

• New treatments inhibiting various stages in this
  process will be initiated
• Atherosclerosis will be successfully treated in
  the coming 30 years by molecular medicine
• The METABOLIC SYNDROME
• hypertension, diabetes, lipid abnormalities,
• overweight

78
(No Transcript)
79
Cerebral Ischemia Treatment-2020-2050

• Atherosclerosis
• Will be treated by dietary changes
• Will be treated by genetic manipulation
• Disease will controlled by 2050
• (You will be age 80 then How long will you live?
  Will science extend your life?)
• What effect will this success on vascular
  neurosurgery?

80
Cerebral Aneurysms Treatment
81
1905-2005
82
1905-2005
83
Koivisto et al, Cerebral Perfusion before and
after endovascular or surgical treatment of
acutely ruptured cerebral aneurysms a 1 year
prospective follow-up study, Neurosurgery
51312-326, 2002
84
Cerebral Aneurysms Treatment-2005

• In neuropsychiatric assessment studies
  conventional surgery will be found to have
  greater morbidity than endovascular treatment for
  similar asymptomatic aneurysms
• Alternatives to conventional surgery will be
  sought
• Minimally invasive surgery and endovascular
  neurosurgery will be important

85
Information Processing, Science 3021133, 2003

• Information flows from front of the prefrontal
  cortex to the back
• Organization of flow is progressive and
  hierarchical
• FMR study in which progressive each region
  making a separate decision before passing on to
  next region
• Phone rings-pick it up at anothers home phone
  rings do not pick it up event context action

86
Cerebral Aneurysms Treatment-2005

• Endoscopic approaches to clip aneurysms will
  become popular as an alternative to endovascular
  treatment
• Complex aneurysms will still require surgery
  until endovascular approaches are developed

87
Minimally Invasive neurosurgical techniques will
become important
88
(No Transcript)
89
(No Transcript)
90
Cerebral Aneurysms Treatment-2015

• Interventional Neuroradiology
• Interventional Neurosurgery
• Endovascular Neurosurgery

91
Mawad et al J. Neurosurg 96474-482, 2002
Aneurysm Treatment with Stent and Polymer
Injection
Giant and Fusiform Aneurysms
92
Cerebral Aneurysms Treatment-2000-2010

• UNRUPTURED ANEURYSMS
• High field Tesla MR Angiography will reveal
  aneurysms in screening of patients before rupture
• Treatment of these aneurysms which are
  controversial now will be initiated by
  endovascular approaches
• Already happening with CT Angio

93
Cerebral Aneurysms Treatment-2000-2010

• Endovascular treatment will become prominent
• Coils will be replaced by glue/plastic/stents
• Now too costly in Brazil Cost will drop
• Some complex aneurysms will still need surgical
  treatment
• Will be done in centers where experience remains

94
Cerebral Aneurysms Treatment-2015

• New endovascular approaches will be developed
• Stents which block aneurysm neck
• Stents which conform to vessel morphology
  determined by 3D imaging
• Stents with genetic programs to cause changes in
  the aneurysm
• Drug eluting stents

95

• Kato, Sano, et al Application of
  three-dimensional CT angiography (3D CTA)
• to cerebral
  aneurysms, Surg. Neurol. 52113-122, 1999

96
(No Transcript)
97
Stents made by Nanotechnology
The development of Nanotechnology will have a
greater impact on society and medicine than the
Internet
98
Cerebral Aneurysms Treatment-2015

• By 2015-2025 most if not all cerebral aneurysms
  will be treated by the endovascular route

99
Cerebral Aneurysms Treatment-2020

• A non invasive medical treatment for cerebral
  vascular spasm will be found
• Hopkins study Inflammatory response

100
JAMA 205 1477, 2005
101
1Olson et al BMC Med Gen 3 7 2002 2Wills et
al Stroke 341370-74 2003

• The Genetic Basis for Aneurysm formation
• Chromosome 19q locus of aneurysm defect1
• Finnish population study showing gene effect in
  families2
• Genetic treatment of aneurysms - 2020?

102
Molecular Basis of Recovery and Rehabilitation
103
Pariente et al, Ann Neurol 50 718-29, 2001
Fluoxetine modulates motor performance and
cerebral activation of patients recovering from
stroke
104
NeurogenesisUse of Stem Cells
105
Neuroscience. 131 257-262, 2005
106
(No Transcript)
107
(No Transcript)
108
MITOTIC CHROMOSOMES
How will medicine be practiced in the 21st
century?
CHROMATIN FIBRES
Study of disorders of cell metabolism and function
NUCLEOSOMES
HISTONES
DNA
109
How Medicine Will Be Practiced in the Future?
110
Neuroscience or Neurosurgery?

• The growth of scientific knowledge is and will be
  exponential
• No single physician can know all this knowledge
• Thus, interdisciplinary and multi-specialty
  integration will become key in providing
  solutions for disease processes
• You will practice in groups

111
Neuroscience or Neurosurgery?

• The future in CNS will be developed by
  neuroscientists working in collaboration to solve
  complex problems
• Surgical approaches will only be of historical
  interest
• Neurobiology will become the focus of disease
  solution.

112
Neuroscience or Neurosurgery?

• Meetings of future will have neurochemists,
  radiation physicists, molecular biologists,
  engineers, computer scientists, neurologists and
  neurosurgeons discussing biological topics and
  developing solutions.
• The neurosurgeon must be a neurobiolgist/neuroscie
  ntist to survive

113
Neuroscience or Neurosurgery?

• As a result
• Educational programs will change
• Specialty designations will change
• Spine physician
• Stroke physician
• Financial relationships among these
  multi-specialty groups will change
• Are you willing and ready to change?

114
Time

• The greatest scientific advances in human
  history have taken place in the last 50 years in
  our life time
• 1 of all recorded human history in time
• 1/130 million th of the history of the known
  universe
• A fraction of a second of all time
• What is really important in life?
• IT ISNT MONEY OR MATERIAL THINGS

115
Thank You for Inviting Me to This Conference

• My best wishes to you for your future
• jamesausman_at_mac.com