Deep Brain Stimulation

Question 1

What is deep brain stimulation?

Answer 1

Procedure in which stimulating electrodes are placed stereotactically into certain deep brain structures
100Hz frequency parameter

Question 2

What is the mechanism of DBS?

Answer 2

Electrodes connected to implanted pulse generator

• electrodes secured to skull
• cable tunnelled around ear down neck to generator which is in front of chest
• battery replacements for generator required every 3-4 years
• rechargeable systems developed with lifespan of 10 years

Question 3

What is DBS used for?

Answer 3

NHS funded

• Parkinson’s (hypokinetic)
• essential tumour (hyperkinetic)
• dystonia (hyperkinetic)

Individual funding requests

• epilepsy
• chronic neuropathic pain

Question 4

What is being experimented with DBS?

Answer 4

• treatment of psychiatric disorders
• dementia
• eating disorders
• disorders

Question 5

What is dystonia?

Answer 5

brain disorder with sustained or repetitive muscle contractions resulting in twisting and repetitive movements/abnormal fixed postures

Question 6

What is the criteria in DBS for Parkinson’s disease?

Answer 6

• idiopathic PD
• 4 classical symptoms (rigidity, tremor, bradykinesia, postural instability)
• do not have sensory issues (as would therefore be related to nerves and would not be Parkinsons)
• do not get weakness/hyper-reflexia (would be affecting pyramidal tract so not idiopathic Parkinsons)
• require MRI scan to check for abnormalities
• no mental disorders
• treated with levodopa (as response to levodopa is good confirmation of Parkinsons)
• still respond to levodopa (DBS will not work if no dopamine neurons available)
• physically fit for surgery
• realistic expectation of surgery (not a cure but will help with motor symptoms)
• age (younger the better?)

Question 7

What symptoms of Parkinsons does DBS treat?

Answer 7

Only the motor symptoms

Question 8

How is DBS carried out for Parkinson’s?

Answer 8

• ensure patient has washed hair with anti-bacterial shampoo, emptied bowels, had good sleep
• patients not on medication so will arrive at hospital slow and stiff
• use MRI scan to work out target site
• connect stereotaxic frame on patient’s head/do 3D printing of skull to create something that fits on after some anaesthetic as frame can be painful
• shave hair off
• drill 4cm hole into skull, insert microelectrode tip to target site
• each brain structure has distinct neurophysiological spiking
• remove microelectrode and insert stimulating electrode
• cap hole, close would, MRI scan to confirm correct electrode site and general anaesthesia for neurostimulator implant
• return home next day, 1 month later return to clinical programme DBS and adjust drug dosage

Question 9

What are the effects of DBS on Parkinsons?

Answer 9

• increases ‘on’ time (time where drug is working - still have to take levodopa but less of it)
• decrease bradykinesia and rigidity
• reduce medication dose
• improves dyskinesia as less drug required
• effectively treats tremor (levodopa not good with tremor)

Question 10

Which brain regions does DBS work on?

Answer 10

• zona incerta (tremor)
• subthalamic nucleus (tremor)
• global pallidus internal (dystonia and tremor)

Question 11

When and how does DBS treat epilepsy?

Answer 11

• when medications are inadequate
• epilepsy surgery not always possible as cannot identify focal brain region (remove seizure origin)
• electrode implanted into anterior nucleus of thalamus as part of brain which spreads seizure
• only reduces do not eliminate seizure frequency
• benefits 50-60% epileptic patients so NICE do not fund, have to make individual funding requests

Question 12

How does DBS treat chronic neuropathic pain?

Answer 12

• treat pain when medications are inadequate
• surgery via lesion to brain regions related to pain pathway is more invasive than DBS
• only reduce NOT eliminate pain experience
• benefits 15-50% of pain in patients

Question 13

What is pallidotomy?

Answer 13

Make a lesion to the globus pallidus use an electrical probe of 80 degrees Celsius for 1 minute

Question 14

What is thalamotomy?

Answer 14

make a lesion to the thalamus using an electrical probe of 80 degrees Celsius for 1 minute

Question 15

What are the 3 types of tremors?

Answer 15

• resting tremor
• Postural tremor (shaking whilst putting hand up)
• Intentional tremor (shaking whilst trying to do something e.g. writing)

Question 16

What is essential tremor?

Answer 16

A brain disorder causing part of body (head and forearms) to tremor uncontrollably
Often genetic

Question 17

What types of causes can induce Parkinsons?

Answer 17

Idiopathic
Vascular Parkinsonism
Drug Induced Parkinsonism - e.g. drugs to be used for schizophrenia

Question 18

What is the function of the thalamus?

Answer 18

Central control as everything leaving the brain and coming up from spinal cord passes through thalamus

Question 19

What happens to levodopa dose overtime?

Answer 19

Dosage increases - have to take it more frequently as effects are worn off quicker
Also dyskinesia worsens as you take more

Question 20

What are some other regions/uses for DBS?

Answer 20

Resistant Depression - Brodmann area 25
Anorexia - hypothalamus
Addiction - nucleus accumbens
Alzheimer’s disease - anterior of fornix

Question 21

What are the pros of DBS?

Answer 21

• proven safe, no deaths
• effective in treating movement disorders
• improves tremor which are levodopa resistant
• effects are reversible and area can be tailored to patient’s clinical status
• patients who have undergone DBS are still candidates for other treatment options - stem cell/gene therapy
• allows decrease in medication/makes medication more tolerable

Question 22

What are the cons of DBS?

Answer 22

• 2-3% risk of brain haemorrhage causing paralysis/stroke/speech impairment (so tell patients week before to stop taking aspirin/heparin)
• small risk of CSF leakage = headaches and meningitis
• 15% risk of temporary problems with transplantation = infection/allergy to implant so have to take it out and redo
• temporary tingling in face/limbs, loss of balance, dizziness, concentration issues
• migration of electrodes from original implantation site
• temporary rebound in worsening of tremor when stimulation stopped
• no absolute guarantee DBS will benefit patients

Question 23

What are the 4 hypothesis for DBS mechanism of action?

Answer 23

1 - inhibition hypothesis
2 - excitation hypothesis
3 - disruption hypothesis
4 - neuro-network modulation hypothesis

Question 24

What is inhibition hypothesis?

Answer 24

• PD due to overactive basal ganglia in STN and op GPi
• DBS can block this removing spontaneous discharge from GPi neurons
• if give GABA agonists/lesion GPi alleviate problem

Question 25

What is excitation hypothesis?

Answer 25

Neurones in the thalamus have an a.p and go from cell body to synapse = orthodromic - too much activation of the cortex - DBS excites afferent axons so creates excitation in the opposite direction towards cell body (antidromic) = 'jamming' of spontaneous activity= reduction of excitation of cortex

Question 26

What is the disruption hypothesis?

Answer 26

- have direct, indirect and hyperdirect pathways (doesn't go through striatum) which all terminate in GPi - by stimulating the GPi you disrupt/block flow before it goes to thalamus stopping GPi functioning

Question 27

What is the neuro-network modulation hypothesis?

Answer 27

- explains delayed effect of DBS - involves neuroprotection, release of astrocytic gliotransmitters, electrotaxis, cortical plasticity which all result in DBS working