BRAIN STIMULATION THERAPIES

Dr.S.Santhosh Goud

Chairperson Dr.D.Ragadeepthi

Brain stimulation therapies involve activating or touching the brain directly with electricity, magnets, or implants to treat neuro psychiatric illness

Other names- neuromodulation/non-pharmacological somatic therapies

16th century seizure induction in psychiatric conditions

1785 therapeutic use of seizure induction inLondon Medical Journal

Father of electrotherapy-G.B.C Duchenne

ELECTRO CONVULSIVE THERAPY VAGUS NERVE STIMULATION TRANSCRANIAL MAGNETIC STIMULATION DEEP BRAIN STIMULATION MISCELLANEOUS

ELECTRO CONVULSIVE THERAPYS.no. Year Procedure Introduced by1 1934 Chemical convulsive

therapyVon Meduna

2 1938 Electro convulsive therapy Cerlette&Bini3 1940 Curare modified therapy Bennet4 1945 Oxygenation during ect Holovachka5 1949 Unilateral non dominant ect Goldman6 1952 Succinylcholine-modified

ectHolmberg&Thesleff

7 1942 Ect in india Brig.E.A.Bennet8 1979 FDA approval for

Depression

The aim of ECT -to induce generalised cerebral seizure activity with an electrical dose that is sufficiently above the seizure threshold to maximize the clinical efficacy of treatment, but not so high that it needlessly contributes to the cognitive effects of treatment

Electrical aspects

Parameter Brief Pulse wave

Sine wave

Current amplitude

0.8A 0.6A

Voltage 160V 120VFrequency 100PPS 50HzWidth 1msecDuration 1sec 0.5secImpedence 200ohm 200ohmEnergy 12.8J 36Jcharge 80mC 300mC

Electrode placement Unilateral vs Bilateral Bi temporal Bi frontal Unilateral(d’Elia RUL)

Frequency of treatment Thrice or twice a week

Matelzky’s multiple monitored ECTs-2 or more ECTs per treatment session, at a frequency of 2 or more

sessions per week

Regressive ECTs-repeated ECTs to produce vegetative state

Stimulus aspects Threshold stimulus-lowest stimulus at

which seizure is produced Effectiveness with supra threshold

stimulus(150%) Threshold is increased with number of

ECT sessions

Determining the stimulus strength Based on age,sex,anesthetic dosage and

concomitant medication Trial method Fixed high charge for all patients

Mechanism of action

EEG changes-electro cerebral silence

Neurochemical changes- Upregulation of 5-HT receptors Decreased DA autoregulation Increased opiods in brain Increased GABA Increased CSF Acetylcholine

Action on second messangersNeuro endocrine changes HPA axisBlood Brain Barrier permeabilityIncreased expression of growth factors

Procedure Informed consent Pre-ect investigations Pre anesthetic precautions NBM for 6 hours prior Void urine Not to apply hair oil,remove hair pins Remove jewellery,contact lens,hearing

aids, dentures Establish venous and airway access

Pre medication,anesthesia and muscle relaxant

Atropine 0.3-0.6mg/i.m 30-45 mins before Methohexitol(0.75-1.0mg/kg)/

thiopentone(2.5mg/kg)Profopol(1.5mg/kg)

Scoline with in a minute of anesthetic agent(0.5-1mg/kg)

Oxygenation(100% 5L/min) through out the procedure

Unmodified ECT With out prior muscle relaxant Common in India, Japan and Nigeria Union health ministry recommended to

ban direct ECT in mental health care bill 2013

Benzodiazepine-modified ECT

Duration of seizure Atleast 25 sec(15secs of motor

seizures(30-60sec optimal) Monitering Seizures(motor seizure duration 30%

shorter than EEG seizure) Ecg vitals

Missed seizures-25-100% increase in dose with proper oxygenation and a 20-40second delay(max 4/session)

Abortive seizures-restimulation after a 60-90 seconds delay

Prolonged seizures-more than 120secs(>90secs of motor seizures)

Terminate by giving iv anesthetic/Benzo with adequate ventilation

ECT emergent delirium-give iv benzo/haloperidol

Prolonged confusion ->1 hour Reduce ect sessions/stop ECT/Switch to

unilateral ECT Headache-analgesics, bodyache-curare Prolonged apnoea –assisted respiration

for 1 hour; Rarely fresh plasma transfusion

The major risks of ECT are those of brief general anesthesia.

There are virtually no absolute health contraindications precluding its use where warranted (Potter & Rudorfer, 1993; Rudorfer et al., 1997).

The most common adverse effects are confusion and memory loss for events surrounding the period of ECT treatment.

The confusion and disorientation seen upon awakening after ECT typically clear within an hour.

Mortality 1 per 10,000

Contraindications Only relative contraindications Raised ICT Recent MI(<3 months) > 6 months not aCI Unstable vascular aneurysm Retinal detachment Pheochromocytoma Anesthetic risk

Cardiac pacemaker is not a contraindication Thyroid dysfunction should be corrected

Indications Major depressive disorder with Suicidal attempt Severe suicidal plans Severe illness refusing food/fluids Stupor Psychomotor retardation psychosis

ECT may be considered as a second- or third-line treatment of a depressive illness that has not adequately responded to antidepressant drug treatment and where social recovery has not been achieved (e.g. an inability to return to work).

70% efficacy in MDD

Mania The treatment of choice for mania is a

mood-stabilising drug plus antipsychotic drug.

ECT may be considered for severe mania associated with:

life-threatening physical exhaustion treatment resistance (i.e. mania that has

not responded to the treatment of choice).

A combination of ECT and a moderate dose of a neuroleptic is extremely effective in rapidly aborting an acute episode of mania

ECT can be recommended for any manic patient,irrespective of the severity or the duration of the illness (Sikdar et al 1994)

Acute schizophrenia The treatment of choice for acute

schizophrenia is antipsychotic drug treatment. ECT may be considered as a fourth-line option, that is, for patients with schizophrenia for whom clozapine has already proven ineffective or intolerable

Effective in 10% cases

Catatonia Catatonia is a syndrome that may

complicate several psychiatric and medical conditions. The treatment of choice is a benzodiazepine drug;most experience is with lorazepam.

ECT may be indicated when treatment with lorazepam has been ineffective.

Delusional disorder Other neuropsychiatric conditions PD and movement disorders Intractable seizures NMS Hypopituitarism Delirium

Number of ECTs There is no evidence to indicate what

number of sessions of ECT gains the best response. Neither is there any evidence to support the practice of giving two extra ECT sessions after the patient is considered to be well enough to discontinue ECT.

Frequency 3 times weekly/Twice weekly Total 6-12 or more when needed No response with 6 sessions-stop ect

ECT in elderly patients with depression Electroconvulsive therapy is a highly

effective treatment for major depressive disorder in the elderly, perhaps even more so than in younger age groups (Benbow, 1987; Devenand & Kruger, 1994).

It is also effective and well tolerated in the old-old(Tew et al, 1999).

Older people tend to have higher seizure thresholds

Older patients may be more susceptible to confusion after ECT

Cognitive function should be assessed at least 24 hours following ECT

If confusion proves to be a problem, consideration should be given to switching from bilateral to unilateral ECT

There is no significant difference in the cognitive outcome of elderly patients with depression treated with ECT or tricyclic antidepressant medication

ECT can be given to patients with dementia and depression without ill effect but they may be at increased risk of post-ECT delirium

ECT in pregnancy the recommended (Heath & Yonkers, 2001):

Obstetric consultation before referral for ECT Routine fetal heart monitoring before and

after each individual treatment when gestational age is beyond the first trimester(obstetric consultation may suggest earlier monitoring in high-risk pregnancies)

case-by-case consideration of intubation, because of the risk of regurgitation, particularly beyond the first trimester.

ECT in children and adolescents No studies only case reports Differ in opinions Safe in 15-17 Case report in 8 year child with

successful resolution of depression Risk benefit ratio

There is evidence that ECT can cause persistent or permanent memory loss (Squire et al, 1981;Weiner et al, 1986; McElhiney et al, 1995; Sobin et al, 1995), which is difficult to distinguish from that caused by illness.

Deficits are usually in recall of both autobiographical memory and public information(knowledge of events in the world)

ECT and Psychotropics No isssues with any anti depressant Antipsychotics except clozapine are safe Reduce anti epileptic dose if possible(only

for mania) Reduce benzodiazepine dose(or shift to

non benzo anxiolytic/for sleep add low dose CPZ)

Lithium???

Focal electrically adminstered seizure therapy(FEAST)-Spellman,2009

Uses direct current/monophasic pulses Different electrode configuration Unidirectional stimulation Focal seizures in prefrontal cortex with

secondary generalization Few side effects

Vagus nerve stimulation

Primarily developed for seizure disorder(1997 FDA approval)

In 2005 approved for MDD Response rate 30% Approved for chronic use only>2yrs

Vagus nerve is a mixed nerve Afferents had connection with NTS and many

other vital centers Zabara(1992) discovered anti convulsant

action of VNS in experimental seizures(pentylene tetrazole) in dogs

His hypothesis VNS prevents or controls motor and autonomic components of epilepsy

Action on mid brain centers Regulation of NE and GABA

A device called a pulse generator, about the size of a pocket watch, is surgically implanted in the upper left side of the chest. (left had few cardiac efferents so low risk of arrhythmias)

Connected to the pulse generator is a lead wire, which is guided under the skin up to the neck, where it is attached to the left-sided vagus nerve.

VNS generator can be controlled by personal computer or digital infra red wand

How it works?? Typically, electrical pulses that last about

30 seconds are sent about every five minutes from the generator to the vagus nerve

The vagus nerve, in turn, delivers those signals to the brain.

The pulse generator, which operates continuously, is powered by a battery that lasts around 10 years, after which it must be replaced.

The device also can be temporarily deactivated by placing a magnet over the chest where the pulse generator is implanted. A person may want to deactivate it if side effects become intolerable, or before engaging in strenuous activity or exercise because it may interfere with breathing. The device reactivates when the magnet is removed.

VNS is indicated for the adjunctive long-term treatment of chronic (more than 2 years) or recurrent depression for patients 18 years of age or older who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments

Side effects Infection Voice changes or hoarseness(SLN&RLN

stimulation) Cough or sore throat Neck pain Discomfort or tingling in the area where the

device is implanted Breathing problems, especially during exercise Difficulty swallowing, dyspepsia

Other uses Anxiety disorders Migraine Alzheimer's disease Fibromyalgia Tinnitus Obesity Lennox-gastaut syndrome Multiple sclerosis

Repetitive trans cranial magnetic stimulation

Thompson 1910

Barker, 1984

Cadwell

DantecMagstim

Common rTMS machines

Repetitive transcranial magnetic stimulation (rTMS) uses a magnet instead of an electrical current to activate the brain.

Typical rTMS session lasts 30 to 60 minutes and does not require anesthesia.

An electromagnetic coil is held against the target area of the brain that is thought to be involved in deserved function. Then, short electromagnetic pulses are administered through the coil.

The magnetic pulse easily passes through the skull, and causes small electrical currents that stimulate nerve cells in the targeted brain region. And because this type of pulse generally does not reach further than two inches into the brain, scientists can select which parts of the brain will be affected and which will not be.

Generally, the person will feel a slight knocking or tapping on the head as the pulses are administered

ADVANTAGES OVER ECT

1. Non invasive procedure

2. Fewer cognitive side effects

3. Patient can drive in and drive out

4. No risk of anesthesia

5. No stigma

6. Less risk for clinician

Changes in excitability and blood flowLow frequency rTMS

< 1 Hz. frequency stimulation Low frequency stimulation for

long duration, induces long lasting inhibition of neuronal excitation called as Long term depression (LTD)

Reduces cerebral metabolism

Reduction in cerebral blood flow

Application on Lt. PFC causes deterioration of mood

High Frequency rTMS

> 1 Hz frequency stimulation High frequency stimulation for

short duration, induces long lasting increase of neuronal excitation called as Long term Potentiation (LTP)

Increases cerebral metabolism

Increase in cerebral blood flow

Application on Lt. PFC causes elevation of mood

PROTOCOLS Protocol A low frequency stimulation (1 Hz) Used for auditory hallucinations on left temporo parietal

region at 90% of MT Protocol B High frequency stimulation ( 2Hz) Used for anxiety disorders, somatisation disorder, OCD,

moderate depressive disorder on left prefrontal region at 110% of MT

Protocol C High frequency stimulation(3Hz) Used for severe depression on left prefrontal region at

110% of MT

TMS diagnostic uses-to measure activity and function of specific brain circuits in humans.

measuring the connection between the primary motor cortex and a muscle to evaluate damage from stroke, multiple sclerosis, amyotrophic lateral sclerosis, movement disorders, motor neuron disease and injuries and other disorders affecting the facial and other cranial nerves and the spinal cord.

The use of single-pulse TMS was approved by the FDA for use in migraine

For neuropathic pain, for which there is high-frequency (HF) repetitive TMS (rTMS) appears effective

For loss of function caused by stroke LF-rTMS of the corresponding brain region has probable efficacy

For treatment-resistant major depressive disorder, HF-rTMS of the left dorsolateral prefrontal cortex(DLPFC) appears effective and low-frequency (LF) rTMS of the right DLPFC has probable efficacy.

For negative symptoms of schizophrenia, HF-rTMS of the left DLPFC has probable efficacy

Hoffman used daily LF-rTMS over temporal lobes to treat hallucinations

Areas of research Rehabilitation of aphasia and motor

disability after stroke Anxiety disorders,obsessive-compulsive

disorder, schizophrenia,substance abuse,addiction, and posttraumatic stress disorder (PTSD)

Amyotrophic lateral sclerosis, multiple sclerosis,epilepsy,Alzheimer's disease, Parkinson's disease, Tinnitus

Side effects The muscles of the scalp, jaw or face may contract

or tingle during the procedure. Mild headache or brief light headedness Possibility of seizure(1 in 1000 patients or 1 in

30,000 treatments) Transient induction of hypomania, transient

cognitive changes Transient hearing loss, transient impairment of

working memory, Induced currents in electrical circuits in implanted

devices

Contraindications Patients with any type of non-removable

metal in their heads (with the exception of braces or dental fillings), or within twelve inches of the coil should not receive rTMS

Deep brain stimulation

Deep brain stimulation (DBS) was first developed as a treatment for Parkinson's disease to reduce tremor, stiffness, walking problems and uncontrollable movements(Limousin 1995)

Internal globus pallidus & Sub thalamic nucleus are the target areas

In DBS, a pair of electrodes is implanted in the brain and controlled by a generator that is implanted in the chest. Stimulation is continuous and its frequency and level is customized to the individual.

DBS has only recently been studied as a treatment for depression or obsessive compulsive disorder

No FDA approval for depression

DBS requires brain surgery. The head is shaved and then attached with screws to a sturdy frame that prevents the head from moving during the surgery. Scans of the head and brain using MRI are taken. The surgeon uses these images as guides during the surgery. Patients are awake during the procedure to provide the surgeon with feedback, but they feel no pain because the head is numbed with a local anesthetic

Once ready for surgery, two holes are drilled into the head. From there, the surgeon threads a slender tube down into the brain to place electrodes on each side of a specific part of the brain.

In the case of depression, the part of the brain targeted is called Area 25(Rostral anterior cingulate). This area has been found to be overactive in depression and other mood disorders.

Another approach bilateral high frequency stimulation of nucleas accumbens

In the case of OCD, the electrodes are placed at anterior limb of internal capsule ,bilaterally (Greenberg)

After the electrodes are implanted and the patient provides feedback about the placement of the electrodes, the patient is put under general anesthesia.

The electrodes are then attached to wires that are run inside the body from the head down to the chest, where a pair of battery-operated generators are implanted.

From here, electrical pulses are continuously delivered over the wires to the electrodes in the brain.

Epidural cortical stimulation Based on principle of cortical regulation

of sub cortical ,limbic regions Shown good results Other indications of DBS Tourette’s disorder Substance use Obesity schizophrenia

Side effects• Bleeding in the brain or stroke• Infection• Disorientation or confusion• Unwanted mood changes• Movement disorders• Lightheadedness• Trouble sleeping

Magnetic seizure therapy

Magnetic seizure therapy (MST) borrows certain aspects from both ECT and rTMS.

Like rTMS, it uses a magnetic pulse instead of electricity to stimulate a precise target in the brain. However, unlike rTMS, MST aims to induce a seizure like ECT. So the pulse is given at a higher frequency than that used in rTMS(100Hz,2T)

Therefore, like ECT, the patient must be anesthetized and given a muscle relaxant to prevent movement.

The goal of MST is to retain the effectiveness of ECT while reducing the cognitive side effects usually associated with it.

It is currently being investigated for the treatment of treatment-resistant depression (TRD), schizophrenia and obsessive-compulsive disorder

Transcranial direct current stimulation

Application of constant weak(< 1mA) for 20mins through scalp electrodes

Induces subthreshold changes in membrane potential thus alters the cortical excitability

Most research for neuro rehabilitation(post stroke aphasia rehabilitation)

Studies in pain and depression Burns over scalp is the only side

effect if current >2mA

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