Assistant Professor of Surgery Director, Functional and Restorative Neurosurgery University of Connecticut

(Benabid et al., 1991; Blond et al., 1992)

DBS  

SURGERY  

Personnel  

Equipment  

Space    

Interdisciplinary  

Collabora>on    

Movement  Disorder  Neurologist  

Neurosurgeon  

Psychiatrist  Electrophysiologist  

Neuropsychologist  

Pa9ent  

APRNs/  PAs  

Anesthesia  Team  

OR  Staff  

Neuro-­‐ICU  Staff  Pa9ent  

DBS Lead Extension Implantable Pulse Generator (IPG)

Test Stimulator Clinician Programmer Pt Controller

Neurosurgeon  

Neurologist  Psychiatrist  

STAGE   PROCEDURE  

BASELINE/PRE-­‐OP  

MRI  (Stereotac>c)  Pt  Evaluated  by  Neurology  Pt  Evaluated  by  Neurosurgery  Pt  Evaluated  by  Neuropsychology  Surgical  Pre-­‐op  Hold  Medica>ons  Target  Selec>on  Trajectory  Planning    

STAGE  1  (2  DAYS)  

CT  Scan  Stereotac>c  frame  placement  Electrophysiology  recording  Electrode  placement  EPG  tes>ng  Post-­‐Op  CT  Scan  Post-­‐Op  X-­‐Ray  Neuro-­‐ICU  Observa>on  Pt  Discharged  to  home  day  1  or  2  

EPG =External Pulse Generator IPG =Implantable Pulse Generator

STAGE   PROCEDURE  

STAGE  2  (14  DAYS)  

IPG  Surgery  Test  impedance  Post-­‐Op  X-­‐Ray  Ini>al  IPG  Programming    Pt  Discharged  same  day  

STAGE  3  (12  WEEKS)  

Wk  2:  Post-­‐Op  visit  with  surgeon  Wk  4:  Post-­‐Op  with  neurologist  

Wk  12:  Post-­‐Op  visits                                Neurologist  and  surgeon  

STAGE  4  (>12  WEEKS)  Post-­‐Op  visits  with  neurologist  for  op>miza>on  of  parameters  

EPG =External Pulse Generator IPG =Implantable Pulse Generator

STAGE   DEFINITION  

1   Unilateral  involvement  only  

1.5     Unilateral  and  axial  involvement  

2   Bilateral  involvement  w/o  impairment  of  balance  

2.5   Mild  bilateral  involvement  with  recovery  on  retropulsion  test  

3  Mild  to  moderate  bilateral  involvement,  some  postural  instability,  physically  independent  

4   Severe  disability,  able  to  stand  and  walk  unassisted  

5   Wheelchair-­‐bound  or  bedridden  except  when  assisted  

UPDRS  Item   Assessment  Scale  Measurement  

Range  

Bradykinesia  subscale  

Score  includes  •  body  bradykinesia  and  hypokinesia  •  le_-­‐  and  right-­‐hand  finger  taps,  opening  and  closing  of        hands,  prona>on/supina>on  of  hands,  and  heel  taps  

0  (not  affected)  to  36  (most  severely  

affected)  

Tremor  subscale  

Score  includes  •  ac>on  tremor  of  right  and  le_  hands  •  res>ng  tremor  in  the  le_  and  right  hands  and  feet  •  res>ng  tremor  of  the  face,  lips,  and  chin  

0  (not  affected)  to  32  (most  severely  affected)  

Rigidity  subscale  Score  includes  •  rigidity  in  the  neck  •  rigidity  in  the  le_  and  right  upper  and  lower  extremi>es  

0  (not  affected)  to  20  (most  severely  affected)  

PIGD  (postural  instability  and  gait  

disorder)  

Score  includes  •  falling,  freezing,  ability  to  walk  •  gait,  postural  stability  

0  (not  affected)  to  20  (most  severely  affected)  

Representa>ve  sample  of  key  measurement  items  from  the  UPDRS  scale  Fahn et al., 1987

Unified  Parkinson’s  Disease  Ra>ng  Scale  (UPDRS)  

Cuny et al, 2002

Ulla et al, 2009

STN

SNr

Sagieal  Sec>on  through  the  Thalamus    

Thalamus

Tremor-­‐  Vim  

Parkinson’s  Disease-­‐  STN  

Dystonia-­‐  Vim  or  GPi  

Emerging  targets:  Subthalamic  white  maeer,  Paralemniscal  Radia>ons,  and  PPN  

Krack  et  al.,  NEJM,  2003  

“On  6me”  more  than  doubled  

54% 51%

71%

50%

0 10 20 30 40 50 60 70 80 90

100 % Improvement

DBS OFF DBS ON

• >800 published articles on DBS in MDJs • Safety and efficacy demonstrated • Long-term benefits

•  The  most  common  movement  disorder  

•  Big  impact  on  life:  –  Socially  –  Professionally  –  Emo>onally  

hep://www.total-­‐diet.com/170-­‐stress-­‐at-­‐work/  

•  Begins  in  one  upper  limb  

•  30%  of  cases  include  cranial  musculature:  head,  voice,  jaw  &  face  

•  Tremor  may  ini>ally  be  intermieent  

hep://www.bartleby.com/107/illus1232.html  

•   4th  most  disabling  disease  worldwide    

• Psychiatric  Disorders    afflict  44  million  in  US  at  cost  of        >  $300  billion  

•   >15%  of  disease  burden  in  US  (more  than  that  of  all  cancers)  

(Saxena et al., 2002)

LF  Responders  =  pa>ents  with  at  least  a  25%  reduc>on  in  YBOCS  at  last  follow-­‐up  

• Forebrain  projec>ons:  Orbitofrontal  &  Prefrontal  cortex  via  ventral  internal  capsule  to  DM  thalamus  &  Amygdala,  Hypothalamus    

• Reciprocal  posi>ve  feedback  loops  Cor>co-­‐striato-­‐pallido-­‐thalamo-­‐cor>cal  circuits    

• Interac>ons  with  the  Papez  circuit  via  pregenual  and  rostral  cingulate  cortex  

IC IC

Caudate Caudate

Putamen

Putamen

AcM

GP

Region  where  Subcaudate  Tractotomy,  Gamma  Capsulotomy,  and  DBS  Targets  Overlap  S.  Haber  

Medial

Orbital

Dorsolateral Premotor Motor

•  10  pa>ents  -­‐  Cleveland  Clinic/Brown  (2003-­‐2006)  •  Only  the  most  severe,  debilitated,  &  highly  treatment  

resistant  pa>ents  were  enrolled  –  Personal  and  professional  disability  –  Suicide  aeempts  –  At  least  five  years  of  depression  –  At  least  five  courses  of  medica>ons  –  Behavioral  Therapy  –  Bilateral  ECT  

•  Contraindica>ons  –  Substance  abuse,  personality  disorder,  psycho>c  disorder  

•  At  one  year  follow-­‐up  2/3  of  pa>ents  had  50%  improvement  in  depression  scores  

46 YOF, post-partum end-stage depression of over 10 years, medication-refractory with over 74

Electroconvulsive shock (ECT) treatments

(Mayberg et al., Neuron, 2005)

HAMD17    Scores  Over  Time  

Scores*  

Pt  1† Pt  2‡ Pt  3† Pt  4‡ Pt  5† Pt  6†

Preop  baseline 29 22 29 24 26 25

1  week  post-­‐op    (acute  s>mula>on)

5 10 12 18 17 12

2  weeks  post-­‐op  (DBS  off) 9 13 23 18 22 n/a

3  months 2 15 14 25 7 14

6  months 5 15 9 23 6 12

*Clinical  response:  decrease  in  HAMD  >50%.  Clinical  remission:  absolute    HAMD  <  8.        †Responders  ‡Non-­‐responders  

(Adapted from Mayberg et al., Neuron, 2005

HDRS17

, Hamilton Depression Rating Scale ; GAF, Global Assessment of Functioning; BDI, Beck Depression Inventory; HDRS

24, Hamilton Depression Rating Scale; MADRS, Montgomery-Asberg Depression Rating Scale (Ward et al., 2010)

Study N Location of stimulation

Baseline Post-DBS

Lozano et al., 2008 20 Cg25 Baseline

HDRS17 24.4 ± 3.5 Mood 11.9 ± 1.5 Anxiety 3.8 ± 2.4

Sleep 3.6 ± 2.0 Somatic 4.9 ± 0.8

12 months 12.6 ± 6.3 5.9 ± 3.7* 1.6 ± 1.9* 2.0 ± 1.3* 3.0 ± 1.4*

Jiménez et al., 2007 1 Inferior thalamic peduncle

Baseline GAF 20 HDRS 33-42 BDI 38

1 week

3 16

1 month 90 8 11

Malone et al., 2009 15 VC/VS Baseline

HDRS24 33.1 MADRS 34.8

6 months 17.5 17.9

Schaepfer et al., 2008 3 NAcc Baseline

HDRS24 33.7 ± 3.8 MADRS 35.7 ± 2.9

1 week 19.7 ± 6.7 24.7 ± 6.7

(Mayberg et al., Neuron, 2005)

CBF decrease

CBF increase

x = -4 y = +28

Baseline CBF PET

All PT vs. NC  

3 mo Post-DBS Surgery

6 mo Post-DBS Surgery  

(Na6onal  Survey  on  Drug  use  and  Health,  2002)          (The  United  Na6ons  World  Drug  Report,  2007)  

•  Chronic  relapsing  disease  •  Psychological  dependence  •  Physical  dependence  •  Withdrawal  syndrome  •  Tolerance  •  Con>nued  use  despite  adverse  

consequences  •  Impaired  control  

(Diagnos6c  and  Sta6s6cal  Manual  of  Mental  Disorders,  4th  Ed)  (Interna6onal  Classifica6on  of  Diseases,  10th  Ed)  

(Stelten et al., 2008)

(Gao  et  al.,  2003)  

•  Case  report  of  a  pa>ent  with  anxiety,  depression,  and  alcohol  dependence  

•  Bilateral  s>mula>on  •  12  month  follow  up  •  Therapeu>c  effects  were:    

–  Slight  anxiety  reduc>on  –  Allevia>on  of  co-­‐morbid  

alcohol  dependence  

(Kuhn  et  al.,  2007)   (Heinze et al., Front Hum Neuro, 2009)