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: skanekar@hmc.psu.edu .