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Imaging of
Neuromodulation
Sangam Kanekar, M.D.
Depts. of Radiology and Neurology
Penn State Milton S Hershey
Medical Center and
.
College of Medicine
ASNR 2015
Conflict of Interest Statement
Neither I nor my immediate family members have a
financial relationship with a commercial organization
that may have a direct or indirect interest in the content.
ABSTRACT
TEACHING POINTS
1. To discuss with illustrations the indications, techniques, imaging appearance, and complication
with commonly used stimulators.
2. To discuss the MR safety and guidelines for these devices
Neuromodulation is the electrical or physical modulation of a nerve to influence the physiologic behavior of
an organ. In this exhibit we present with illustrations the indications, techniques, imaging appearance, and the
complications of commonly used stimulators:
1. Deep brain stimulators: for treatment-refractory movement disorders such as Parkinson’s disease,
essential tremor, and dystonias. DBS applications are being explored for depression, Alzheimer’s disease,
and addictions.
2. Spinal cord stimulation: for failed back surgery syndrome, refractory angina, peripheral vascular disease,
phantom limb pain, spinal lumbar stenosis, postthoracotomy pain syndrome, chronic head and neck pain,
and chronic visceral abdominal pain.
3. Vagus nerve stimulation: is a well-established treatment of medically refractory epilepsy.
4. Sacral neuromodulation: Lower urinary tract dysfunction (overactive bladder and nonobstructive urinary
retention).
5. We also discuss the various complications associated with neuromodulations.
6. Finally we discuss the MRI compatibility of these devices.
History
Neuromodulation is the electrical or physical modulation of a nerve to influence
the physiologic behavior of an organ. Over a last decade more and more of the
NM devices have been used in patient for different indications. Neuromodulation
is based on the revolutionary concept that paresthesia-inducing electrical
stimulation could be analgesic. Its historical basis emanates from Melzack and
Wall’s gate control theory of pain proposed in 1965. Two years later, Shealy and
Mortimer designed an electrode and successfully implanted it in a patient to
alleviate cancer-related pain. Medtronic Inc. (Minneapolis, MN) introduced the
first commercially available SCS system in 1968, which used radiofrequency
coupled with dorsal-column stimulators. The genesis of modern DBS occurred in
Melzack and Wall’s
1973, the result of a report by Hosobuchi.
gate control theory
In this exhibit we present with illustrations the indications, techniques, imaging appearance, and
the complications of commonly used stimulators:
1. Deep brain stimulators
2. Spinal cord stimulation
3. Vagus nerve stimulation
Sacral neuromodulation
We also discuss:
5. various complications of NM:
infection, migration, broken leads, wrong placement
6. Finally we discuss the MRI compatibility (1.5 v/s 3 T) of these devices.
Types of Neuromodulations
Chemical neuromodulation: refers to injection or infusion of a pharmacologically active
substance within the nervous system. It targets specific receptors with precise effects. E.g.
procaine into the globus pallidus before creating a permanent lesion with ethanol for tremor in
advanced PD. Although chemical neuromodulation is principally used in experimental models,
these examples in humans are important advances in understanding the basic pathophysiology of
movement disorders and its potential application as a therapeutic tool.
Cryogenic Neuromodulation: still in the experimental basis. It showed that cooling various
structures of the brain to 0 to 10C produced a reversible inhibition of neural activity, and that
cooling below –20 could create a permanent lesion.
Ultrasound Neuromodulation: Similar principle that of cryogenic but using sound waves for
modulation.
Magnetic Neuromodulation: Transcranial magnetic stimulation (TMS) is a noninvasive
technique used for measuring and modulating cortical plasticity. TMS is delivered via an
electrical coil placed on the scalp, which generates a magnetic field that traverses the cranium
and induces an electrical field in the cortex. High-frequency rTMS (>1 Hz) increases cortical
excitability28 and lowfrequency rTMS (<1 Hz) reduces cortical excitability. rTMS is currently
approved for use in medication-refractory depression in the United States and Canada. It has
been studied in neurologic diseases such as PD, tremor, dystonia, tics, spasticity, and epilepsy.
Electrical Neuromodulation (DBS)
Deep Brain Stimulation (DBS) has revolutionized the treatment of treatment-refractory
movement disorders by allowing precise anatomical neuromodulation of select
intracranial nuclei while the direct stimulation of spinal cord or peripheral nerves results
in decreased excitability, increase in electrical threshold and transient slowing of
conduction velocity.
Principles and circuits
Neuromodulation by DBS is a result of electrical currents that flow into and out of neurological
substrates, including cells, axons, dendrites, and glial cells, leading to polarization of these
elements. The current is generated by a pulse generator and is delivered to the tissue via
electrodes implanted in the brain.
Current
• Axons farther away from the electrode require higher amplitudes for activation.
• Larger axons are stimulated at lower thresholds than smaller axons.
• For a particular stimulation amplitude and pulse width, larger-diameter axons are
stimulated farther away from the stimulation electrode than smaller-diameter axons.
• With increasing pulse widths the difference in activation radius around the
stimulation electrode between larger-diameter and smaller-diameter axons becomes
smaller.
Principles and circuits
1. The ventral intermediate nucleus of the
thalamus is the preferred of target to treat
tremors. This nucleus receives projections from
the spinal cord and deep cerebellar nuclei and
has reciprocal connections with the cerebral
VL thalamic Nu
cortex. It is “intermediately” positioned
Putamen
between the motor (ventral oral) and sensory
(ventral caudal) thalamus and medially adjacent
Globus
Pallidus
Subthalamic Nu
to the posterior limb of the internal capsule.
Stimulation of Vim thalamus suppresses tremor
immediately
Substantia Nigra
Blue lines represent stimulatory connections, red dotted lines
represent inhibitory connections.
2. The GPi is a common target for the surgical treatment of dystonias and the medicationrefractory, motor symptoms of PD. It represents the primary outflow of basal ganglia.
3. The STN is commonly targeted for the treatment of PD. As part of the intrinsic circuitry of the
basal ganglia, it provides excitatory, glutamatergic output to the GPi. Stimulation of the STN will
produce immediate tremor arrest and reduced rigidity that returns when stimulation is stopped.
Bradykinesia can be more difficult to assess and is often susceptible to lesional effects from
macroelectrode insertion and repetitive highfrequency stimulation testing.
Placement of the DBS largely depends on the symptoms of the patient.
SYMPTOMS
ANATOMIC NUCLEUS TARGETED
Non-parkinsonian essential tremors
Ventrointermediate nucleus (VIM) of the thalamus
Dystonia and symptoms associated with Parkinson’s
disease (rigidity, bradykinesia, tremors),
Globus pallidus internius and subthalamic nucleus
OCD and depression
Nucleus accumbens
Incessantly pain
Posterior thalamic region or periaqueductal gray
Parkinson plus patients
Two nuclei simultaneously subthalamic nucleus and
tegmental nucleus of pons
For epilepsy
Anterior thalamic nucleus
Nociceptive pain
periaqueductal gray and periventricular gray
Neuropathic pain
Internal capsule, ventral posterolateral nuclei and
ventral posteromedial nucleus
treatment resistant depression
subgenual cingulate gyrus, nucleus accumbens, ventral
capsule/ventral striatum, inferior thalamic peduncle, and
the lateral habenula. superolateral branch of the medial
forebrain bundle
Schizophrenia
septal areas
DBS for the treatment of movement disorders such as Parkinson's disease, dystonia and tremor has mainly
targeted structures in the basal ganglia. The translational 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) model for Parkinson's disease has highlighted the internal globus pallidus (GPi) and the subthalamic
nucleus (STN) as safe and efficacious targets. High-frequency (130–185 Hz) DBS for PD have shown
substantial improvements in symptoms. The preferred target for dystonia and spasmodic torticollis is the GPi.
Blinded, controlled GPi trials have shown 30–50% improvements in patients over 12 months.
Classic MRI appearance of DBS for PD pt.
Edematous changes in the left deep gray matter
nuclei following DBS.
High-frequency (1001 Hz)
stimulation is used to
simulate the chronic therapy
that is typically used in the
outpatient clinic setting.
Low frequencies (2–10 Hz)
can be used to preferentially
activate large, myelinated
axons like those of the
pyramidal tract encountered
in the posterior limb of
internal capsule.
DBS complications
Complications can be divided into early and late. Early complications mainly involve ischemia
and intracranial hemorrhage, namely intraparenchymal hematoma, subdural hematoma, and
epidural hematoma. Late complications predominantly include infection, lead migration, for
which the published incidence to date is 4-5% (42) and frank electrode breakage (rare)
Moderate pneumocephalus in the frontal
region bilaterally following DBS placement.
Large acute left frontal lobe hematoma and
pneumocephalus in a pt with severe headache
following following DBS placement.
DBS complications
10/24/2012
frank electrode breakage in
the neck.
01/12/2013
Coronal CT scan of the brain shows superior
migration of DBS lead from the subthalamic nucleus.
DBS complications
Cerebritis and cerebral abscess in the right frontal lobe due to infected DBS lead.
Diffuse meningitis, subdural empyema due to infected bilateral DBS leads.
Spinal cord stimulation
Spinal cord stimulation (SCS) is a technique of electrical neuromodulation in which one
or more electrodes are placed in the epidural space of the spine.
Common indications include:
1. Failed back surgery syndrome (FBSS)
is the most common,
2. Complex regional pain syndrome
(CRPS) is the second one.
3. Other uses:
refractory angina,
peripheral vascular disease,
phantom limb pain,
spinal lumbar stenosis,
postthoracotomy pain syndrome,
chronic head and neck pain, and
chronic visceral abdominal pain,
FBSS
CRPS
Neuropathy
visceral pain
PVD
Msc
CRPS, complex regional pain syndrome
FBSS, failed back surgery syndrome;
PVD, peripheral vascular disease.
“Pain Mechanisms”
Ronald Melzack and Patrick Wall introduced their "gate control" theory of pain "Pain Mechanisms: A New
Theory". Small nerve fibers(pain receptors) and large nerve fibers ("normal" receptors) synapse
on projection cells (P), which go up the spinothalamic tract to the brain, and inhibitory interneurons (I)
within the dorsal horn.
When no input comes in, the inhibitory
neuron prevents the projection neuron from
sending signals to the brain (gate is closed).
small-fiber
inhibitory neuron
large-fiber
gate is closed
small-fiber
inhibitory neuron
large-fiber
gate is closed
small-fiber
inhibitory neuron
large-fiber
Normal somatosensory input happens when
there is more large-fiber stimulation. Both the
inhibitory neuron and the projection neuron
are stimulated, but the inhibitory neuron
prevents the projection neuron from sending
signals to the brain (gate is closed).
gate is open
Nociception (pain reception) happens when
there is more small-fiber stimulation. This
inactivates the inhibitory neuron, and the
projection neuron sends signals to the brain
informing it of pain (gate is open)leading to
PAIN.
Neuromodulation of the peripheral pain
mesencephalic locomotor area
stimulation
Epidural
stimulation
Afferent
stimulation
pharmacological
stimulation
Afferent
Efferent
Spinal cord stimulation
Two common types of electrodes used are: cylindrically shaped percutaneous electrodes (PEs)
and paddle-type surgical ones (SE).
Spinal cord stimulation
Spinal cord stimulation (SCS) is based on the gate theory, which had been published by Melzack
and Wall in 1965. Although SCS evolved as a consequence of this theory, it does not explain the
mechanism of action of SCS accurately. Imaging either plain radiograph or CT/CT myelogram is
predominately done to see for the location of the leads and diagnose associated complications if
any.
Spinal cord stimulation
The complication rate of SCS is high, ranging from 8% to 75% in the literature. They may occur
intraoperatively as well as in the early or late postoperative period.
Complication
Electrode migration
Hardware malfunction
Cerebrospinal fluid leakage
Pain at the pulse generator site
Infection
Subcutaneous hematoma
Electrode fracture
Nerve root or spinal cord injury
Epidural hematoma
Allergic reaction
Skin erosion
electrode migrations
outside the spinal
canal.
MRI studies should be avoided in patients with implanted SCS devices because the
magnetic field may produce lead migration, damage the IPG or can cause a rapid
increase in tissue temperature close to the electrode tip. We recommend avoiding MRI
studies in those patients in whom non-MRI compatible devices were implanted.
However, there are new MRI compatible devices commercially available.
Spinal cord stimulation
Complication
Intraoperative neurologic injury: It is a serious
complication, which may cause direct penetration of
the spinal cord with the Touhy needle or cause cord
contusion. The dissection of epidural adhesions can
result in nerve root injury during SE implantation.
The risk of neurologic injury is largely related to the
volume and stiffness of the paddle.
Electrode migration or displacement is the most
common complication of SCS. Electrode
displacement is suspected when there is a change in
the area of induced paresthesia, which is associated
with a loss of pain control. Lead migration and its
direction can be accurately confirmed by
radiography.
Infection: Subdural or extradural abscess are
mostly seen due to poor surgical techniques.
Thick extradural enhancement surrounding the
spinal stimulator due to infection.
Spinal cord stimulation
Complication
Temporary pain: due to the healing process related to disruption of body tissue during the
implantation procedure usually subsides after 7-14 days.
Complex Regional Pain Syndrome
CRPS, formerly recognized as reflex sympathetic dystrophy, is frequently misunderstood,
misdiagnosed, and mistreated.
CSF leakage: is more common with paddle type of electrodes due to accidental dural puncture
during implantation. Rarely dura may torn during laminectomy. The most common clinical
presentation is positional headache in the early postoperative period, as any CSF fistula. There
may be fluid accumulation at the IPG site. Small dural punctures typically heal spontaneously,
whereas blood patch can be used to treat refractory and severe puncture-related postural
headache.
Arachnoiditis
Arachnoiditis is a postsurgical complication and is believed to be caused by scarring and
adhesions located intraspinally. Because of the phenomenon that develops, pain from the
adhesions.
Spinal cord stimulation
T10
T11
T11
Intraoperative
Xray
shows upper margin of
the SCS at T10. Patient
remained symptomatic.
1 week follow up CT
scan shows inferior
migration
and
herniation
of
the
stimulator through the
surgical defect.
Extradural abscess and myositis due to
infected SCS.
Complication
Peripheral Nerve (PNS)/ Peripheral Field
Stimulation(PNFS) for Neuropathic Pain
Chronic neuropathic pain syndromes are frequently very difficult to treat. One of the
surgical options is direct electrical stimulation of the affected nerve by placing a
stimulating electrode over the nerve or under the skin in the area of pain. PNS remains
an attractive option because of its minimally invasive nature and an ability to provide
focal neuromodulation. The common indications of PNFS can be classified based on
the pain type and pain location. For PNS, the pain must be in the distribution of a single
nerve, whereas for PNFS it is more important for the pain to be in an area that can be
covered by the commercially available length of electrodes. Larger areas of pain can be
better treated by other neuromodulation modalities such as SCS, targeted brain
stimulation (such as deep brain stimulation or motor cortex stimulation), or intrathecal
drug-delivery systems.
For some unknown reasons application of PNS and PNFS are not as robust as that of
other neuromodulation.
Vagus nerve stimulation
The concept of electrically stimulating the vagus nerve to treat seizures was first reported in
1883, by James L. Corning. However, it was not until approximately a century later that Penry
implanted the first vagal nerve stimulator (VNS) device in a human. The U.S. Food and Drug
Administration (FDA) approved VNS implantation in 1997 as adjunctive treatment in multidrugresistant epilepsy. In July 2005, VNS therapy was approved by the FDA for the treatment of
adults with major depression unresponsive to medical treatment.
Principle: Vagus nerve arises from the medulla and carries
both afferent and efferent fibers. The afferent vagal fibers
connect to the nucleus of the solitary tract which in turn
projects connections to central nervous system. The exact
mechanism how vagus nerve stimulation modulates mood
and seizure control is not understood.
It is proposed that the alteration of norepinephrine release
by projections of solitary tract to the locus coeruleus,
elevated levels of inhibitory GABA related to vagal
stimulation and inhibition of aberrant cortical activity
by reticular activation system.
Vagus nerve stimulation
Vagus nerve stimulation (VNS) is a safe and cost-efficient therapy for the treatment of medically
refractory epilepsy. It has few side-effects, guaranteed compliance, no drug interaction and is safe
in all age classes.
Vagus nerve stimulation
Vagus nerve stimulation (VNS) is a safe and cost-efficient therapy for the treatment of medically
refractory epilepsy. It has few side-effects, guaranteed compliance, no drug interaction and is safe
in all age classes.
39 year old patient with intractable seizures due to
mesiotemporal sclerosis. Patient refused surgical treatment.
Patient was successfully treated with vagal nerve stimulation. If
these patients have to go for MRI of brain or any other part of
the body 1) we have to make sure that leads and electrodes are
not broken and 2) the stimulator needs to be turned off before
patient enters the magnet.
Vagus nerve stimulation
Common side effects seen with VNS include cardiac
arrhythmia, sleeo apnea. Rarely due to stimulation of the
superior and recuurent laryngeal nerv patient may
expoeriened alteration of the voice, coughing, pharyngitis
and throat pain. Imaging mostly plain radiographs is
performed to see the disruption of the electrodes for preMRI
evaluation. Broken leads are contraindication for an MRI as
it can cause local burns and electrical disruption.
Broken lead
Sacral nerve stimulation
Spinal cord injury (SCI) is a devastating event whose sequelae of paralysis, paresthesia, and
bowel and bladder dysfunction have significant lifelong consequences. There are an estimated
12,000 new cases of SCI annually in the United States alone. Neurogenic voiding dysfunction is a
major contributor to the morbidity and mortality of SCI. Spina bifida and myelomeningocele are
equally debilitating conditions that have a similar spectrum of symptoms including voiding
dysfunction. Normal lower urinary tract function consists of low pressure storage and voluntary,
coordinated expulsion of urine. Neurogenic voiding patterns range from bladder atony to hyperreflexia with detrusor external sphincter dyssynergia (DESD) or synergia
Sacral nerve stimulation
A significant amount of research has focused on the effect of sacral neuromodulation (SNM) on
afferent sensory nerve fibers, with the dominant theory being that electrical stimulation of these
somatic afferent fibers modulates voiding and continence reflex pathways in the central nervous
system (CNS). The control of sensory input to the CNS is thought to work through a gate-control
mechanism. Sacral nerve stimulation long has been a reliable form of neuromodulation for
various types of lower urinary tract dysfunction including overactive bladder and nonobstructive
urinary retention.
pudendal nerve neuromodulation
The pudendal nerve is a peripheral nerve that is composed mainly of afferent sensory fibers from
sacral nerve roots S1, S2, and S3. Most afferent sensory fibers are contributed by S2 (60%) and
S3 (35%).
Principles: Because the pudendal nerve carries such a large percentage of afferent fibers,
neuromodulation of the pudendal nerve is an attractive option for refractory detrusor
hyperreflexia.
Research trials
Extensive research is in progress to use the various neuromodulation techniques in the various
neurological disorders.
1. The limbic system is involved in some of the most challenging neurobehavioral disorders
known to medicine, including disorders of mood and anxiety such as depression and
posttraumatic stress disorder (PTSD), substance abuse and dependence, and disorders of
cognition and memory such as Alzheimer disease. Advances in surgical neuromodulation of
the limbic circuitry underlying these disorders offer a new hope for treatment.
2. Neuromodulation of the cingulate gyrus has been shown to be effective for pain and
obsessive-compulsive disorder (OCD).
3. PTSD is an anxiety disorder that develops following a life-threatening or an integritythreatening traumatic event, and often includes perceptual, cognitive, affective, physiologic,
and psychological features. The estimated lifetime prevalence of PTSD in the United States is
approximately 6.8%. Koenigs and Grafman showed that 40% of veterans who suffered brain
injury in combat develop PTSD unless the amygdala is injured. The amygdala seems to be
responsible for the encoding and retrieval of the memories associated with the traumatic
events. In this sense, it is responsible for the symptoms and suffering associated with PTSD.
If it is assumed that DBS can functionally reduce the activity of a cerebral target and that
activity in the amygdala seems to be responsible for PTSD development, DBS of the
amygdala may treat the symptoms of PTSD.
Research trials
MEMORY
Alzheimer disease is the most common form of progressive dementia, and currently there is no
cure. Pharmacologic agents such as acetylcholinesterase inhibitors and N-methyl-Daspartate
receptor antagonists are used to delay. High frequency stimulation of the anterior nucleus of the
thalamus (AN) in rats has been shown to increase hippocampal neurogenesis and to reverse
experimentally suppressed hippocampal neurogenesis. These findings suggest that DBS not only
alters neuronal activity but also produces long-term neuronal changes that may potentially
enhance memory formation. DBS of the AN and functionally related regions may be used to
enhance memory.
Preliminary results show that DBS to specific
nuclei within the limbic system may be at least
as successful as traditional pharmacologic
therapies.
MRI safety
1. Use manufacture’s manual to find out if
stimulator is MRI COMPATIBLE.
2. Make sure that leads or electrodes are NOT
BROKEN OR DISTORTED. Usually
confirmed by plain radiographs.
The most important precautions that must be taken when performing MR imaging in these patients are the
following: 1) Use a 1.5T MR imaging system; 2) stop the DBS stimulation for the duration of the scanning;
3) use only a transmit-receive-type radiofrequency head coil (NOT a whole-body radio-frequency coil, a
receive-only head coil, or a head-transmit coil that extends over the chest area); and 4) select MR imaging
parameters with a specific absorption rate (SAR) that does not exceed 0.1 W/kg in the head. 5) An MRI
procedure SHOULD NOT be performed in a patient with that has a broken lead wire because higher than
normal heating may occur at the break or the lead electrodes, which can cause thermal lesions. These lesions
may result in coma, paralysis, or death.
Contraindication
MRI is contraindicated in patients with DBS who will be exposed to magnetic
resonance imaging (MRI) using a full body transmit radio-frequency (RF) coil,
a receive-only head coil, or a head transmit coil that extends over the chest
area.
Conclusion
For last two decade, application of the various neuromodulation
techniques have gained wide acceptance. Most commonly used
neuromodulators are DBS, SCS, vagal nerve and sacral nerve
stimulations for various causes.
It is important for radiologist to understand the normal
appearance, expected post-operative changes and diagnose the
complications as soon as possible. This exhibit is an insight into
imaging of neuromodualtion.
THANK YOU
Questions and suggestions to: [email protected]
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