Stimulation Magnetism

Magnetism

A New Method for Stimulation of Nerve and Brain

Mark

Hallett,

MD, Leonardo G.

Cohen,

^MD

SELECTEDCASE

A34-YEAR-OLD^{woman waswell until} age 22 _years, when she

experienced

transient numbness of both hands. At age 24 years she had her first bout of

urinary incontinence,

^a

problem

^that

continued

intermittently.

At age 26 years she

experienced

^{double and}

"faded" vision.

Subsequently,

^{she noted}

the

gradual development

of weakness andstiffness^{of both}

legs, making

^walk-

ing

^difficult. Examination showed de- creasedvisual

acuity

^and

pale

^{discs on}

funduscopic

evaluation. Tonewasmod-

erately

^{increasedinthe}

legs,

^{but there}

was

only

minimal weakness in distal flexors. Sensation was

minimally

^im-

paired distally

^{in the}

legs.

^Reflexes

werebrisk and therewerebilateral Ba- binski's_responses.

Visual evoked

potentials

^{were in-}

creasedin

latency, right

^sidemorethan

left. Brain-stem

auditory

^evoked

poten-

tials from the

right

^{ear wereabnormal.}

Somatosensory

^evoked

potentials

^were

normal.

Magnetic

stimulation^{of themo-} tor^areas of the brain showed

delayed

motor evoked

potentials

^{in abductor}

pollicis

^{brevis muscles}

bilaterally (Fig 1)

^{and in the}

right

tibialis anterior

(Fig 2);

^{therewere no}responses inthe left tibialis anterior.

Responses

^inabductor

pollicis

^{brevis muscles} with electric stimulationoverthe cervical

spine

^and

intibialis anteriormuscles withelectric stimulation_overthe upperlumbar

spine

were

normal, indicating

that the abnor¬

malities observed with brain stimula¬

tionweredue_to

delays

^{of centralmotor}

conduction.

Magnetic

^resonance

imag¬

ing

^scanofthebrain showed^numerous

areas of

periventricular

^increased

sig¬

nal.

Cerebrospinal

^{fluid showed}

oligo-

clonalbands.

PROBINGTHECENTRAL MOTOR PATHWAYS

The

diagnosis

^of

^multiple

^sclerosisin

this

patient

^is

definite,

^with

signs

^and

symptoms

of multifocal disease in the central nervous

system

disseminated

overtime.The

laboratory

^dataarecon¬

sistent withthe

diagnosis.

^Inthe contin¬

ued absence ofa

laboratory

^test

specific

for

multiple sclerosis,

information from evoked

potentials

is useful in

confirming multiple demyelinating

^{lesions incen¬}

tral nervous system

pathways.

^Addi¬

tionally,

sensoryevoked

potentials

^are

ableto

identify

^{lesionsin the nervous}

system

^thatare

clinically

silent. For^ex¬

ample,

visual evoked

potentials

may well showa lesion in the visual

path¬

ways in the absence of visual

signs, symptoms,

^or

history

of visual distur¬

bance. Thiscan

help

provethe multifo-

cality

^{neededtoestablishthe}

diagnosis.

Sensory

^evoked

potentials

^evaluate

the central_sensory

pathways,

^{but until}

recently

there has beennoway^to

probe

thecentralmotor

pathways.

^{A method}

for

doing

^thisshouldbe useful in multi¬

ple

sclerosis becausethe disease com¬

monly

^{involves the}

corticospinal

^tract.

Our

patient

^{isa casein}

point. Magnetic

stimulation of her brain documented

slowing

ⁱⁿ

corticospinal pathways.

^Two

points

^deserve

emphasis. First,

^cortico¬

spinal

^{conduction was abnormal when}

somatosensory

^{conductionwas}

normal, indicating

^that

somatosensory

^evoked

potentials

^donot

probe

^motor

pathways

and_motorand sensory function^canbe disturbed

differentially. Second,

^corti¬

cospinal

^{conductiontothearms wasab¬}

normal in theabsenceof definite clinical

manifestations, indicating

^thatmagnet¬

ic stimulationcanreveal

clinically

^silent

lesions.

ELECTRICSTIMULATION

Stimulation^ofthe^nervous

system

^is

almostasoldas

electricity

itself. Elec¬

tric stimulation has been used in the

hope

^of

curing hemiplegia

^{andeven in}

attempts

^{toraise thedead.1}

Today,

^{it is}

used as transcutaneous electric nerve

stimulation for relief of

pain.

^Stimula¬

tion has foundasecurerolein theneuro¬

logical diagnosis

of neuromuscular dis¬

eases. For

example,

^{in nerve con¬}

duction

studies, evaluating

^theconduc¬

tion

speed

^ofnerve

impulses gives

^some

indication of the

integrity

^{of the}

^myelin

sheath.

Itwas

only

^ashort time ago thatMer- ton and Morton2 demonstrated that it

was

possible

^{to stimulate}

electrically

the motor areas of the human brain

through

^{the intact}

scalp. They

^{used a}

brief, high-voltage

electric shockto^ac¬

tivate themotorcortex and

give

^risetoa

brief, relatively synchronous

^musclere¬

sponse, the ^motor evoked

potential.

Thus,

^{it became}

possible

^{forthe first}

time_to

study

^the

speed

of conduction in central _motor

pathways.

^The

latency

from brain stimulation to muscle re- From the Human MotorControl Section, Medical

NeurologyBranch, National Institute of Neurological Disorders andStroke,National Institutes ofHealth,^Be- thesda,Md.

PresentedJuly^{13, 1988, atClinicalCenterGrand} Rounds,National Institutes of Health.

Reprintrequests^toNationalInstitute ofNeurological

Disorders andStroke, NationalInstitutes ofHealth,Bldg 10,Room5N226, Bethesda,MD 20892(DrHallett).

Downloaded From: http://jama.jamanetwork.com/ on 05/16/2012

sponse ^can be divided into two

parts,

the central and the

peripheral.

^{The time}

of the

peripheral path

^{can be obtained}

from the

latency

^ofamuscleresponse^to stimulationoverthe

spine

^{orfrom tak¬}

ing

^{half the}

latency

^{ofanFwaveinthat}

muscle.(The^{Fwaveisa"late}

response"

after stimulation of thenerve

owing

^to

activation ofthemotor^neuronsfrom the antidromic

volley

^inthe

nerve.)

^{If the}

peripheral latency

^{is subtracted from}

the total

latency,

^{theremainderis the}

central conduction time.

A

problem

with electricstimulation^is that it is

painful.

^The

pain

^{isnot very}

different from that induced

by

^stimula¬

tion of

peripheral

nerves,but^{it is}suffi¬

cienttolimit its clinical

acceptability.

MAGNETIC STIMULATION

Only

^a few years after noninvasive electric stimulation of ^{the brain was}

demonstrated,

^{Barker et al3 showed}

that it was

possible

^{to stimulate both}

nerve and brain

magnetically.

^{A mag¬}

netic

pulse

^was

generated by passing

^a

brief, high-current pulse through

^acoil

of wire. The

technique

^{hadtheinterest¬}

ing advantage

that the stimulation itself

was

painless,

^{or at least caused much}

less

pain

than electricstimulation.

Why

^should

magnetic

stimulation be less

painful

than electric stimulation?

With both

methods,

^the

underlying

^neu¬

ral tissue can be activated

only by

^a

current

crossing

^{the membraneof the}

excitable cells. Electric ^current pro¬

duced

by

direct electricstimulation falls offas afunction of the

impedance

^{of the}

tissue between the

stimulating

^elec¬

trodes and the neural tissue.

Skin, bone,

and subcutaneous tissue have

high

^im¬

pedances. Hence,

^to deliver sufficient electric_{current to}theneural

tissue,

^itis

necessary todeliver much

higher

^elec¬

tric currentstothe

skin, thereby

^acti¬

vating pain receptors.

^A

magnetic ^field, however, penetrates

^all

body

^tissues

without

alteration, falling

^{off in}

magni¬

tude

only

^as the inverse square of the distance.

Thus,

^{for the same current}

generated

^atthe level ofthe neural tis¬

sue, the current

generated

^{at the skin}

will be less than that used for electric stimulation.

For

magnetic stimulation,

^a

brief, high-current pulse

^is

produced

^inacoil

of

wire,

^{called the}

"magnetic

coil."4,5^A

magnetic

^{field is}

produced

with lines of flux

passing perpendicularly

^{to the}

plane

of the coil. An electric field is in¬

duced

perpendicularly

^tothe

magnetic

field. ^In a

homogeneous medium,

^the

electric field will_causecurrent toflowⁱⁿ

loops parallel

^{to the}

plane

of the coil.

The

loops

^{with the}

strongest

^current

will benearthecircumferenceof the coil itself. The

loops

become weaknearthe

Arm Normal

Patient

C-7

C3

17.5

500u.V

[_

5ms

Fig¹.—Compoundmuscle actionpotentials^{in the}right^abductorpollicis^{brevis inanormal}subject^andthe patient.^Inboth,the uppertraceis the response after electric stimulation^overthe seventh cervical vertebral

spineand the lowertraceis aftermagneticstimulation of thescalpin the left centralregion(over^themotor

cortexfor theright hand).Latencies oftheresponses(in milliseconds)^areindicatedby^{thenumbersonthe}

traces.Responsesof the normalsubject^andpatient^aresimilar with electric stimulation of thenerveroot, but

aredifferent withmagneticstimulation of the brain. Thelatencyafter brain stimulation exceeds3SDs above the normalmean.

Fig 2.—Compoundmuscle actionpotentials^intheright^tibialisanteriorin^anormalsubject^{and the}patient.^In both,the uppertraceis the response after electric stimulation^overthe first lumbar vertebralspine^{and the} lowertraceis aftermagneticstimulation of thescalp^atthevertex(over^themotor cortexfor theleg).^{Note the}

differenceintime scales(5milliseconds per division for the uppertracesand 10 milliseconds per division for the lowertraces).Latencies of the responses(inmilliseconds)^areindicatedbythe numbersonthetraces.

Responses^{ofthe normal}subject^andpatient^aresimilar with electricstimulation of thenerveroot,butare

quitedifferent withmagneticstimulation ofthe brain.

Normal Patient

Cz

I-\

70

500

nV|_

5^ms 10ms

500U.V I 200

^vbs

10ms

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Fig ^{3.—A round} magnetic^coil positioned ^{on the} scalp ^{of a} subject for stimulation of hand motor

representation^{areasin thebrain.}

centerof the coil andnocurrent atall is

generated

^{atthecenteritself.}

Nerve Stimulation

Magnetic

stimulation has been tested toseeif it could

replace

electric stimula¬

tion of

peripheral

^nerves.It is essential that the

electromyographer

^{know ex¬}

actly

^{where thenerveis}

being

^stimulat¬

ed so that the distance between the stimulation site and the

recording site,

orbetweentwostimulation

sites,

^canbe

measured forcalculationof the conduc¬

tion

velocity.

^{As afirst}

approximation,

thenerveisstimulated^nearthe circum¬

ference of the

coil, verifying

^the

phys¬

ics.5,6

Unfortunately,

^{it isnot}

possible

^to

predict exactly

where the stimulation will_occur, whichseemstobemoreofa

problem

^forsomesites than for others.

Thus,

^{itnow seemsthat}

magnetic

^stim¬

ulation_cannotbe used for routinenerve

conductionstudies.7

Magnetic

stimulation _may ^{be useful} for

activating deep proximal

^nerves

thataredifficulttoactivate with electric stimulation. Insome

applications,

^such

as activation ofthe brachial

plexus

^at

Erb's

point,

electric stimulation is

pain¬

ful and the site ofnerve activation is

imprecise.

^Inother

applications,

^suchas

nerveroot

stimulation,

^the

only

way to activate thenerve

electrically

^is

by plac¬

ing

^{a needle}

deeply

^{near the nerve.}

Magnetic

stimulationcanoften activate

deep proximal

^{nerves with reduced}

pain.

The site of stimulation isnot^cer¬

tain, but, compared

^withelectric stimu¬

lation,

^{this isnota}

disadvantage (except

with needlestimulation). ^Withthe

long

distance between the stimulation site and the

recording

^{site in}

proximal

^nerve

stimulation,

^{it isnotascriticaltoknow}

the

precise

stimulationsiteasit is with shortdistances.

Magnetic

stimulation of

proximal

^nerves should be valuable in studies ofnerveconduction in Guillain- Barré

syndrome,

^{and thereare}

already suggestions

^{of its}

utility

^inthe

study

^of

radiculopathies.8 Magnetic

stimulation appearsabletoactivate the facialnerve nearits exit fromthe brainstem,^which shouldbe useful for

evaluating patients

withfacialnervedisorders suchasBell's

palsy.9,10

Brain Stimulation

Stimulation of the brain is the tech¬

nique

^inwhich

magnetism

has the clear¬

estrole in clinical

neurophysiology.

^We

arenotcertain howtofocus the stimula¬

tion ona

precise point,

but this is not

always

necessary.To

study

^centralcon¬

duction

velocity,

^{it is}

only

necessary to make surethat themotor areas ofthe brainareactivated. If the coilis

placed

flatonthetop^{of the}

head,

^{with itscen¬}

ter at thevertex,^the

edges

overlie the

regions

of the handmotorareasbilater¬

ally (Fig

^3), and this is a

satisfactory placement

^for

studying

^conduction times.1112 The motor ^area is activated either

directly

^or

synaptically

^{from ad¬}

jacent

^areas.13

When

magnetic

stimulation is _per¬

formed,

^themuscletobe activatedcan

beat restor

voluntarily contracted;

^con¬

tractionfacilitates the_responseconsid¬

erably."15 Gradually increasing

^theam¬

plitude

of stimulation will also

produce

^a

larger

^muscleresponse. The

amplitude

continuestogrowwith

higher

^{levels of}

stimulation and often does _not

plateau

within the _range of the stimulator.

When the

amplitude plateaus,

^{or nears}

the maximal

output

^{of the}

stimulator,

the

amplitude

of the muscle action_po¬

tential is

typically

about half the value obtained with directnervestimulation.

Contraction of the musclenot

only

^facili¬

tatesthe

amplitude

^{of the}response,but also causes adiscrete step decrease of about2.5millisecondsinthe

latency

^of

response.

The results of

magnetic

stimulation of the brainaresimilar_tothose of electric stimulation. One

difference, however,

is that the

latency

^ofresponse, bothat rest and with muscle

contraction,

^is

shorter with electric stimulation. The

explanation

of this difference_{appears to} be related_tothenatureof the descend¬

ing volley

^{in the}

corticospinal

tract pro-

duced

by

stimulation.1617With electric

stimulation,

^but

typically

^notwithmag¬

netic

stimulation,

^{there is an}

early

^D

wave that reflects direct activation of

descending

^axons. With both electric and

magnetic stimulation,

^{there isa se¬}

ries of later I waves that

apparently

reflect

synaptic

^activation of the corti-

cospinal

^{neurons. A muscle} response will_appear

only

^afterthe

alpha

^moto-

neurons in the

spinal

^{cord are raised}

abovetheir

firing

^threshold.For clinical purposes,it is

important

^tocontrol the state of activation of the muscletoget

reproducible

normal values.

Itis

fairly

easy toobtain

good

^activa¬

tion of the hand with

magnetic

^stimula¬

tion.With the limited_powerofcurrent

magnetic stimulators, however,

^{it is}

sometimes difficult to obtain

optimal

stimulation ofthe

leg

motor area,which lies

deep

^{in the}

interhemispheric

fissure.

It is

possible

^toactivate the brain fo-

cally

^with

magnetic

stimulation.18,19This

permits

noninvasive

mapping

^{of themo¬}

torcortex,^whichwedemonstratedwith electric

stimulation,20,21

^{and the tech¬}

nique

^{used with}

magnetic

stimulation is similar.22 In our recent

studies,18

^the

most accurate

topographical

map ^was

generated

^witha

butterfly-shaped

^coil.

Face,

^distalarm,

proximal

arm,and

leg

areascanbedifferentiated.

Magnetic

brain stimulation will al¬

most

certainly

^findan

important

^{role in}

teaching

^{us moreabout the}

physiology

of the human brain. Brain stimulation

was

used,

^for

example,

^to

study

^{the time}

courseofactivation of themotorcortex

asitprepares to

generate

^thecommand

to

produce

^a

voluntary

movement.23 Stimulation of the motor areas of the brain

produces

^amuscleresponse,buta more

general

^reaction of the brain to stimulation_maybeatransient

interrup¬

tion of function. An

appropriately

^timed

stimulus will

delay

^an

expected

^motor

response,24

^andan

appropriately

^timed

stimulus over

occipital

^{cortex will dis¬}

rupt^visual

processing

^forabout 50 milli¬

seconds.25 ^It takes ^visual information about 100millisecondstoreach theoc¬

cipital

cortex,^{andavisualstimulus}pre¬

sented

briefly

^{willnotbeseenifa}mag¬

netic stimulus is ^delivered to the

occipital

^{cortex about 100} milliseconds after the visual stimulus.

Safety

Magnetic

stimulation _appears ^safe.

The

physical properties

^{of the}

magnetic

stimulus will not

damage

tissue. The

question

is whether the stimulation will affect brainfunctionineither the short term ^or the

long

^{term. As far as we}

know at

present,

^this

question

^{is the}

same for both electric ^and

magnetic

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Stimulation. As noted

above,

^{it does}

seem that stimulation interferes with brain

function,

^atleast

focally,

^forape¬

riod ofmilliseconds. This is

ordinarily

not

noticeable,

^{andthere isnoevidence}

of malfunctionafter this short

period.

We

compared electroencephalograms

before and after electric and

magnetic stimulation,

both in normal

subjects

^and

in

patients,

^{and foundno}

changes.26

^No

long-term psychological

^or intellectual deficit has

been

^seen.Atheoreticalcon¬

cern

might

^be whether the stimulation

causes

kindling,

^the

development

^ofan

epileptogenic

^focusatthe site of stimu¬

lation. There ^are many ^{reasons to} be¬

lieve that this willnotoccur.5

Potential Clinical

Applications Magnetic

stimulation of the brain is still

experimental

^and

regulated by

^the

Food and

Drug

Administration. Its clin¬

ical

utility

^{is clear}in assessmentofcen¬

tral conduction times in

multiple

^sclero¬

sis,27,28 amyotrophic

^lateral

sclerosis,29

and

degenerative

^ataxic disorders.30 Electric stimulation has revealed con¬

duction abnormalities incervical _spon-

dylosis,31

^and

magnetic

stimulation should beuseful^aswell. A

good

^dealof

information has accruedabout^theuseof

magnetic

stimulation in

multiple

^sclero¬

sis. ^The

yield

of abnormal studies in definitecasesis about

79%, comparable

tothe

yield

of visual evoked

potential

studies.27Inaseries of definite_cases,all weak muscles and half of

strong

^muscles

showed

abnormality.28 Additionally, magnetic

stimulation should be

useful,

asiselectric

stimulation,

^for

monitoring

the

integrity

^{of the}

corticospinal

^tract

during spinal

^cord

surgery32

^{and inter-}

ventional

neuroradiology.33

^{In these}

roles,

^{it will}

complement

somatosenso¬

ryevoked

potentials

that monitor

only

sensory

pathways.

We^aregratefultoHenryMcFarland, MD, ^for referringthepatient^andtoB.J. Hessie for editori¬

alassistance.

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