Deep Brain Stimulation

Question 1

What is the procedure for deep brain stimulation

Answer 1

• This is the procedure in which stimulating electrodes are placed sterotatically into certain deep Brain structures
• the electrodes are connected to an implanted pulse generator which is batter powered
• the electrodes are then secreted to the skull and a cable tunnelled around th year down to the neck to the pulse generate situated in front of the chest
• battery replacements happen every 3-4 years whereas rechargeable systems have been developed to have a lifespan of 10 years

Question 2

How much does deep brain stimulation cost

Answer 2

• Device £12,200
• £7,800 for surgery
• So total cost is around £20,000

Question 3

What is currently NICE approved for deep brain stimulation

Answer 3

• Parkinson’s disease (hypokinetic movement)
• essential tremor (hyperkinetic movement)
• dystonia (hyperkinetic movement)

Question 4

What type of movement is essential tremor and dystonia

Answer 4

Hyperkinetic

Question 5

Define essential tremor

Answer 5

• Brain disorder causing part of the body such as the head and forearms to tremor uncontrollably

Question 6

Define dystonia

Answer 6

• Brains disorder with sustained or repetitive muscle contractions resulting in twisting and repetitive movements or abnormal fixed postures

Question 7

In what diseases can you get deep brain stimulation if you ask for individual funding requests

Answer 7

Epilepsy
chronic neuropathic pain
- this is when the consultant has to put forward a case as to why you should get it

Question 8

describe and name the different types of tremor

Answer 8

there are two main categories these are resting tremor and action tremor

Resting Tremor
- this is when you have a tremor while resting

Action tremor

• either postural, kinetic and intention
• a postural tremor is a tremor when you life a limb such as an arm - holding something against gravity
• Kinetic - occurs with voluntary movement
• Intention - occurs with goal directed movement and worsens as approaching the target

Question 9

resting tremor indicates….

Answer 9

parkinsons disease unless proven otherwise

Question 10

what are the 4 classical symptoms of Parkinson

Answer 10

tremor
bradykinesia
rigidity
postural instability

Question 11

What is the criteria for parkinsons patients in order to get deep brain stimulation

Answer 11

• Idiopathic Parkinson’s disease 4 classical symptoms – tremor, bradykinesia, rigidity, postural instability
• Do not have sensory issues such as numbness and tingling
• Do not get weakness or hyperreflexia
• Require an MRI scan – check for no abnormalities in brain such as brain tumour
• No mental disorders
• Still Levodopa responsive (DBS will not work as patient is burnt out with no DA neurones to have an effect)
• Physically fit for surgery
• Realistic expectation of surgery (not a cure but to help with motor symptoms, PD will eventually catch up)
  age
• Younger patients benefit more from DBS but older patients can still be treated
• DBS only treats the motor symptoms and no the non-motor symptoms (such as gait or balance, cognitive problems and depression)

Question 12

what does the basal ganglia do

Answer 12

• Nuclei in our brain to decide to make movements and stop unwanted movements

Question 13

What does the thalamus do

Answer 13

• Central control unit, as everything is leaving the brain and coming up from spinal cord to pass through the thalamus

Question 14

What are the targets in Parkinson’s for deep brain stimulation

Answer 14

 Subthalamic nuclei. = targets tremor
 Thalamus. = targets dystonia and tremor
 Globus pallidus interna. = targets dystonia and tremor

Question 15

Describe how deep brain stimulation works

Answer 15

• Patients are not on medication for this procedure so stiff and slow when arrive at hospital
• Using MRI scan to work out the target site
• Connect a stereotaxic frame on a patients head
• Drill a 4cm hole in the skull and then insert the microelectrode tip to the presumptive target site
• Each brain structure as a distinct neurophysiological spiking and spike background patterns
• Once the target site has been located microelectrode is removed and the stimulating electrode is inserted
• Cap hole, close wound, MRI scan to check electrode at correct site, then general anaesthesia for neuro-stimulator implant
• Return home next day then return to the clinical 1 month alter to programme DBS and adjust drug dosage
• Patient is awake

Question 16

What does deep brain stimulation do to Parkinson’s

Answer 16

• Increase on time
• Decrease bradykinesia and rigidity
• Reduces medication dose 1/3 less
• Improves dyskinesia as less drug required
• Effectively treats tremor (L dopa not good with tremor)

Question 17

Describe how deep brain stimulation improves the on and off effect of parkinsons

Answer 17

• When L dopa kicks in this is the on time and you can walk normally
• Then drug disappears and then if you want to walk and move again then take L dopa again
• Become tolerant to it the one time becomes shorter
• Then eventually when you take it you get dyskinesia after a short on time – cant really control your movement
• DBS rises the line of bradykinesia up therefore you need a smaller amount of the dose of L dopa for its effect to last longer

Question 18

describe how deep brain stimulation can be used for epilepsy

Answer 18

• treatment for epilepsy when medications are inadequate
• electrode is implanted into the anterior nucleus of the thalamus as this is the part of the brain that causes then seizure to spread
• this reduces seizure frequencies but does not eliminate them

Question 19

Describe how deep brain stimulation can be used to treat neuropathic pain

Answer 19

• Surgery via lesion brain regions related to the pain pathway is more invasive than DBS
• Only reduce not eliminate pain experience
• Benefit 15-20% of pain patients

Question 20

what are the pros of DBS

Answer 20

• Proven safe
• More than 140,000 patients have been implanted with DBS systems
• Can improve tremor that are l dopa resistant
• The effects are reversible and can be tailored to a patients clinical status
• Provides continuous symptom control 24 hours a day for years
• Patients who have undergo DBS are still candidates for other treatment options such as stem cell or gene therapy when they become available
• Allows a decrease in medication

Question 21

What are the cons of DBS

Answer 21

• 2-3% risk of brain haemorrhage that can cause paralysis, stroke and speech impairment
• A small risk of cerebrospinal fluid leakage causing headaches and meningitis
• 15% risk of temporary problems with transplantation (infection, allergy to implant)
• May experience temporary tingling in the face or limbs, loss of balance, dizziness, concentration issues
• Migration of electrode from original implantation site
• Temporary rebound in worsening of tremor when stimulation is stopped
• No guarantee DBS surgery will benefit patients even though large percentage report significant improvement

Question 22

Name the brain region where DBS is targeted for

• tremor
• dystonia
• pain
• epilepsy
• depression
• anorexia
• addiction
• alzheimers
• tourettes syndrome

Answer 22

Other Uses:
 Tremor - subthalamic nuclei and thalamus targeted.
 Dystonia (uncontrollable muscle contraction) – globus pallidus interna.
 Pain – Sensory thalamic nuclei, anterior cingulate gyrus.
 Epilepsy - Anterior thalamic nuclei.
 Depression – Nucleus accumbens, subcallosal cingulate (brodmann area 25)
- anorexia - hypothalamus
- addiction - nucleus accumbens
- Alzheimers disease - anterior of the fornix
- Tourette syndrome - thalamic centromedian

Question 23

what are the 4 hypothesis for the mechanism of action of DBS

Answer 23

• Inhibition hypothesis
• Excitation hypothesis
• Disruption hypothesis
• Neuro-network modulation hypothesis

Question 24

Describe Inhibition hypothesis theory

Answer 24

• This is the idea that Parkinson’s disease is due to overactive basal ganglia neurones in the STN and or/GPi
• DBS can block this and remove spontaneous discharge from GPi neurones
• This hypothesis agrees with anatomical lesioning and pharmacological intervention (GABA agonists)
• DBS inhibits the local neuronal firing removing the spontaneous discharge from GPi

Question 25

Describe excitation hypothesis

Answer 25

- DBS excites afferent axons antidromically resulting in jamming the spontaneous activity - DBS inhibits the local neuronal firing removing the spontaneous discharge from thalamus

Question 26

Describe disruption hypothesis

Answer 26

- The GPI receive input from the direct(GABA) and indreict(GABA) and hyperdirect pathway (glutamate) - DBS can activate axon terminals causing extensive release of NTs such as GABA and glutmate - DBS dissociates inptus and outputs in the stimulated nucleus thus disrupting and blocking the abnroaml information flow through the GPi - DBS disrupts abnormal information flow through the GPi

Question 27

Describe Neuro-network modulation hypothesis

Answer 27

- Far more complex - Suggest that there are other things such as neuroprotection release of astrocytic gliotransmitters, electrotaxis and cortical plasticity - They suggest this as if the other hypothesis were true we would see the changes straight away but we don’t and DBS takes time to work (days)therefore these things must be involved