Chapter to specific targets in the brain (brain

Chapter 4                      Deep Brain Simulation Deep brain stimulation (DBS)is a neurosurgical procedureinvolving the implantation of a medical device called a Neurostimulators(sometimesreferred to as a ‘brain pacemaker’), which sends electrical impulses, throughimplanted electrodes,to specific targets in the brain (brain nuclei) forthe treatment of movement and neuropsychiatric disorders. DBS in select brainregions has provided therapeutic benefits for otherwise-treatment-resistantdisorders such as Parkinson’sdisease, essential tremor, dystonia, chronic pain, majordepression and obsessive–compulsivedisorder (OCD). Despite the long history ofDBS, its underlying principles and mechanisms are still not clear.DBSdirectly changes brain activity in a controlled manner, its effects arereversible (unlike those of lesioning techniques), and it is one of only a fewneurosurgical methods that allow blinded studies.The Foodand Drug Administration (FDA) approved DBS asa treatment for essential tremor and Parkinson’sdisease in 1997,dystonia in2003, and OCD in 2009.

 DBS is also used in research studies totreat chronic pain, PTSD,andhas been used to treat various affective disorders, including majordepression; none of theseapplications of DBS have yet been FDA-approved. While DBS has proven to beeffective for some patients, potential for serious complions and side effects existsThe deep brain stimulation system consists ofthree components: the implanted pulse generator (IPG), the lead, and anextension. The IPG is a battery-poweredneurostimulator encased in a titanium housing, which sends electrical pulses tothe brain that interferes with neural activity atthe target site. The lead is a coiled wire insulated in polyurethane withfour platinum-iridium electrodesand is placed in one or two different nuclei of the brain.

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The lead isconnected to the IPG by an extension, an insulated wire that runs below theskin, from the head, down the side of the neck, behind the ear to the IPG,which is placed subcutaneously below the clavicle or,in some cases, the abdomen. TheIPG can be calibrated by a neurologist, nurse,or trained technician tooptimize symptom suppression and control side-effects. DBSleads are placed in the brain according to the type of symptoms to beaddressed. For non-Parkinsonian essential tremor,the lead is placed in the ventrointermediate nucleus (VIM) of the thalamus;for dystonia andsymptoms associated with Parkinson’sdisease (rigidity, bradykinesia/akinesia,and tremor),the lead may be placed in either the Globuspallidus internus or the subthalamic nucleus; for OCD and depression tothe nucleus accumbens;for incessant pain to the posterior thalamic region or periaqueductalgray; for Parkinson plus patients to two nucleisimultaneously, sub thalamic nucleus and tegmental nucleus of pons, with theuse of two pulse generators; and for epilepsy treatment to the anteriorthalamic nucleus.

4.1 ComponentsAll three components are surgically implanted inside thebody. Lead implantation may take place under local anesthesia or with thepatient under general anesthesia (“asleep DBS”) such as for dystonia.

A hole about 14 mm indiameter is drilled in the skull and the probe electrode is inserted stereotactically. During the awake procedurewith local anesthesia, feedback from the patient is used to determine theoptimal placement of the permanent electrode. During the Asleep procedure, intraoperative MRI guidance is used fordirect visualization of brain tissue and device. The installation of theIPG and extension leads occurs under general anesthesia. The right side of thebrain is stimulated to address symptoms on the left side of the body and viceversa.4.2 Applications4.2.

1Parkinson’s diseaseThe use of DBS as a treatment for Parkinson’sdisease dates from 1987. Parkinson’s diseaseis a neurodegenerativedisease whose primary symptoms are tremor, rigidity, bradykinesia,and postural instability. DBS does not cure Parkinson’s, but it can helpmanage some of its symptoms and subsequently improve the patient’s qualityof life.

 At present, the procedure is used onlyfor patients whose symptoms cannot be adequately controlled with medications,or whose medications have severe side-effects.  Its direct effect on the physiology ofbrain cells and neurotransmitters iscurrently debated, but by sending high frequency electrical impulses intospecific areas of the brain it can mitigate symptoms and directly diminishthe side-effects induced by Parkinson’s medications, allowing a decreasein medications, or making medication regimen more tolerable.There are few sites in the brain that can betargeted to achieve differing results, so each patient must be assessedindividually, and a site will be chosen based on their needs. Traditionally,the two most common sites are the subthalamicnucleus (STN) and the globuspallidus interna(GPi), but other sites,such as the caudal zona incerta andthe pallidofugal fibers medial to the STN, are being evaluated and showpromise.In the United States DBS is approved by theFood and Drug Administration for the treatment of Parkinson’s. DBS carriesthe risks of major surgery, with a complication rate related to the experienceof the surgical team. The major complications include hemorrhage (1–2%) andinfection (3–5%). 4.

2.2Chronicpain:Stimulationof the periaqueductalgray and periventriculargray for nociceptive pain, and the internal capsule, ventral posterolateral nucleus, and ventral posteromedial nucleus for neuropathic pain has produced impressive resultswith some patients, but results vary and appropriate patient selection isimportant. One study of seventeen patients with intractable cancer painfound that thirteen were virtually pain-free and only four required opioidanalgesics on release from hospital after the intervention. Most ultimately didresort to opioids, usually in the last few weeks of life. DBS has alsobeen applied for phantom limb pain. 4.2.

3 Major depression and obsessive-compulsive disorderDeep brainstimulation has been used in a small number of clinical trials to treatpatients suffering from a severe form of treatment-resistant depression (TRD). A number of neuroanatomical targets havebeen utilised for deep brain stimulation for TRD including the subgenualcingulate gyrus, posterior gyrus rectus, nucleusaccumbens, ventralcapsule/ventral striatum, inferior thalamic peduncle, and the lateralhabenula. A recently proposed target of DBS intervention in depression isthe superolateral branch of the medial forebrain bundle (slMFB), its stimulation lead to surprisinglyrapid antidepressant effects in very treatment resistant patients. The smallpatient numbers in the early trials of deep brain stimulation for TRD currentlylimit the selection of an optimal neuroanatomical target. There isinsufficient evidence to support DBS as a therapeutic modality for depression;however, the procedure may be an effective treatment modality in the future. In fact, beneficial resultshave been documented in the neurosurgical literature, including a few instancesin which deeply depressed patients were provided with portable stimulators forself-treatment. A systematicreview of DBS for treatment-resistant depression and obsessive–compulsive disorder identified 23 cases—9 for OCD, 7 fortreatment-resistant depression, and 1 for both.

It was found that “abouthalf the patients did show dramatic improvement” and that adverse eventswere “generally trivial” given the younger psychiatric patientpopulation than with movements disorders. The first randomized controlledstudy of DBS for the treatment of treatment resistant depression targeting theventral capsule/ventral striatum area did not demonstrate a significantdifference in response rates between the active and sham groups at the end of a16-week study. DBS fortreatment-resistant depression can be as effective as antidepressants, withgood response and remission rates, but adverse effects and safety must be morefully evaluated. Common side-effects include “wound infection,perioperative headache, and worsening/irritable mood and increasedsuicidality”.4.2.

4 Tourette syndromeDeep brainstimulation has been used experimentally in treating adults with severe Tourette syndrome that does not respond to conventionaltreatment. Despite widely publicized early successes, DBS remains ahighly experimental procedure for the treatment of Tourette’s,and more study is needed to determine whether long-term benefits outweigh therisks. The procedure is well tolerated, but complications include”short battery life, abrupt symptom worsening upon cessation ofstimulation, hypomanic or manic conversion, and the significant time and effortinvolved in optimizing stimulation parameters”.41 As of 2006, there were five reports inpatients with TS; all experienced reduction in tics and the disappearance ofobsessive-compulsive behaviors. The procedureis invasive and expensive, and requires long-term expert care. Benefits forsevere Tourette’s are not conclusive, considering less robust effects of this surgeryseen in the Netherlands.

Tourette’s is more common in pediatric populations, tending to remit in adulthood,so in general this would not be a recommended procedure for use on children.Because diagnosis of Tourette’s is made based on a history of symptoms ratherthan analysis of neurological activity, it may not always be clear how to applyDBS for a particular patient. Due to concern over the use of DBS in Tourette syndrome, the Tourette Association of America convened a group of experts to developrecommendations guiding the use and potential clinicaltrials of DBSfor TS. Robertsonreported that DBS had been used on 55 adults by 2011, remained an experimentaltreatment at that time, and recommended that the procedure “should only beconducted by experienced functional neurosurgeons operating in centres whichalso have a dedicated Tourette syndrome clinic”.

 According toMalone et al (2006), “Only patients with severe,debilitating, and treatment-refractory illness should be considered; whilethose with severe personality disorders and substance abuse problems should beexcluded.” Du et al (2010) say that”As an invasive therapy, DBS is currently only advisable for severelyaffected, treatment-refractory TS adults”.Singer (2011) says that”pending determination of patient selection criteria and the outcome ofcarefully controlled clinical trials, a cautious approach is recommended”.

 Viswanathan et al (2012) saythat DBS should be used in patients with “severe functional impairmentthat cannot be managed medically”.4.3 MechanismsThe exact mechanism of action of DBS is not known. There are a varietyof classes of hypotheses to explain the mechanisms of DBS: 1.     Depolarization blockade: Electrical currents blockthe neuronal output at or near the electrode site.2.

     Synaptic inhibition: This causes an indirectregulation of the neuronal output by activating axon terminals with synapticconnections to neurons near the stimulating electrode.3.     De-synchronization of abnormal oscillatory activityof neurons.4.     Antidromic activation either activating/blockadingdistant neurons or blockading slow axons.4Deep brain stimulation represents an advance on previous treatmentswhich involved pallidotomy (i.e.

, surgical ablation of the globus pallidus) or thalamotomy(i.e., surgical ablation of thethalamus).

 Instead, a thin lead with multiple electrodes is implanted inthe globus pallidus, nucleusventralis intermedius thalami(Vim) or the subthalamic nucleus and electric pulses are used therapeutically.The lead from the implant is extended to the neurostimulator under the skin in the chest area.               Chapter5Cochlear ImplantsA cochlear implant (CI)is a surgically rooted electronic device that provides a intellect of sound toa person who is intenselydeaf or severely hard of hearing inboth ears; as of 2014 they had been used experimentally in some people who hadacquired deafness in one ear after learning how to speak. Cochlear implantsbypass the normal hearing process; they have a sound processor that resides onthe outside of the skin (and generally worn behind the ear) which containsmicrophones, electronics, battery, and a coil which transmits a signal to theimplant.

The implant has a coil to receive signals, electronics, and an arrayof electrodes which is placed into the cochlea,which stimulate the cochlear nerve.The method in which the device is implantedis usually done under generalanesthesia. Menaces of the proceduresinclude mastoiditis, otitis media (acuteor with effusion), shifting of the implanted device requiring a secondprocedure, damage to the facial nerve,damage to the chorda tympani,and wound infections. People may experience problems with dizziness and balancefor up to a few months after the procedure; these problems generally resolve,but for people over 70, they tend not to.”There is low to moderate quality evidencethat when CIs are implanted in both ears at the sa1me time, they improve hearing in noisyplaces for people with severe loss of hearing.

There is some suggestion thatimplanting CIs to improve hearing may also improve tinnitus butthere is some risk that it may cause people who never had tinnitus to get it.”There is argument around the devices; much ofthe strongest objection to cochlear implants has come from the Deaf community.For some in the deaf municipal, cochlear implants are an affront to their culture, which assome view it, is a minority threatened by the hearing majority.       5.1 parts of the ear 5.1Parts:Cochlear implants bypass most of the peripheralauditory system which receives soundand converts that sound into whereabouts of stereocilia on hair cells inthe cochlea; “Themovement of the stereocilia causes in influx of potassium ions thatarouses the hair cells cellsto release the neurotransmitter glutamate,which makes the cochlear nerve sendsignals to the brain, which makes the familiarity ofsound. Instead, the devices pick up sound and digitize it, convert thatdigitized sound into electrical signals, and transmit those signals toelectrodes embedded in the cochlea.

“The electrodes electrically stimulate the cochlear nerve, triggeringit to send signals to the brain. There are several systems available, butgenerally they have the following components: ·        one or more microphonesthat pick up sound from the environment·       a speech processor whichselectively filters soundto prioritize audiblespeech·       a transmitter that sendspower and the processed sound signals across the skin to the internal deviceby electromagneticinduction,Internal: 5.2 The internal part of a cochlear implant(model Cochlear Freedom 24 RE)·        a receiver/stimulator, which receives signalsfrom the speech workstation and converts them into electric impulses.·        an electrode array rooted in the cochlea    5.2 Surgical procedure·        Thesurgical procedure most often used to implant the device is called mastoidectomy with facial recess slant (MFRA).

 If a person’sindividual anatomy prevents MFRA, other approaches, such as through the suprameatal triangle are used. “A systematic literature review publishedin 2016 found that studies comparing the two approaches were generally small,not randomized, and retrospective so were not useful for makinggeneralizations; it is not known which approach is innocuous or more effective.·        Theprocedure is frequently done under general anesthesia. Risks of the proceduresinclude mastoiditis, otitis media (acuteor with effusion), shifting of the implanted device requiring a second technique,damage to the facial nerve, damage to the chorda tympani,and wound infections.

“11·        “The rateof complications is about 12% for minor hitches and 3% for major complications;major complications include infections, facial paralysis, and device failure.To dodge the risk of bacterial meningitis, which while low is about thirty times as high comparedto people who don’t undergo CI procedures, the FDA commends vaccination priorto the procedure. The rate of transient facial nerve palsy is estimated ·        to beapproximately 1%. Device failure requiring reimplantation is estimated to occur·        in 2.

5-6%of the time. Up to one-third of people experience disequilibrium, vertigo, orvestibular paleness lasting more than 1 week after the technique; in peopleunder 70 these symptoms commonly resolve over weeks to months, but in peopleover 70 the problems tend to persist.”·        Cochlearimplants are only appropriate for people who are deaf in both ears; as of 2014a cochlear implant had” been used experimentally in some people who had assimilateddeafness in one ear after they had learned how to state, and not a soul whowere deaf in one ear from birth; clinical studies as of 2014 had been too smallto draw oversimplifications from.

” 5.3Efficiency:A 2011 AHRQ review of the evidence of theeffectiveness of CI in people with bilateral hearing loss – the device’sprimary use – found low to moderate quality data that presented: speechperception in noisy conditionswas much better for people who had implants in both ears done at the same time,compared to people who had only one; that no conclusions could be drawn aboutchanges in speech perception in quiet conditions and health-relatedquality-of-life. There was only one good study equaling planting implants inboth ears at the same time, to implanting them sequentially; this study foundthat in the sequential approach, the 2nd implantation made no change, or madethings worse. “A 2012 review found that the ability tocommunicate in spoken language was better, the earlier the implantation wasdone; it also found that overall, the efficacy of cochlear implants is highlyvariable, and that it was not possible to accurately predict which childrenwill and will not acquire spoken language successfully. “A 2015 review, examining whether CIimplantation to treat people with bilateral hearing loss had any effecton tinnitus, “foundthe quality of evidence to be poor, and the results variable: overall totaltinnitus suppression rates varied from 8% to 45% of people who received CI;decrease of tinnitus was seen in 25% to 72%, of people; for 0% to 36% of the peoplethere was no change; increase of tinnitus occurred in between 0% to 25% ofpatients; and in between 0 – 10% of cases, people who didn’t have tinnitusbefore the procedure, got it. “5.4 UsageAs ofDecember 2012, approximately 324,000 cochlear implant devices had beensurgically implanted.

In the U.S., roughly 58,000 devices were implanted inadults and 38,000 in children.5.

5 CostIn the United States, “the overall cost of getting cochlear implantswas about $100,000 as of 2017.18 Some or all of this may be covered by healthinsurance. In the UnitedKingdom, the NHS covers cochlear implants in full, as doesMedicare in Australia, and the Department of Health19 in Ireland, Seguridad Social in Spain and Israel, and the Ministry of Health or ACC (depending on the cause of deafness) in New Zealand. According to the US NationalInstitute on Deafness and Other Communication Disorders, the estimated total cost is $60,000 per personimplanted.

“A study by Johns Hopkins University determined that for athree-year-old child who receives                                                  CONTENTS Chapter                  title                                                                              Page No1.                                  INTRODUCTION                                                              1                                               1.1 BRAIN                                        1.

2FUNCTIONS OF BRAIN                                                     2-8                               2.                                 BRAINIMPLANTS                                             2.1 DEFINITION                                                                       9                                         2.

2 PURPOSE                                                                             10                                         2.3 USES                                                                             103.                                 LITERATURESURVEY                                                 11-17           4.                                DEEP BRAINSTIMULATOR                                                                                4.1 COMPONENTS                                                                  18                                        4.2 APPLICATIONS                                                                19-235.                              COCHLEAR IMPLANTS                                           5.

1PARTS                                                                         25                                      5.2SURGICAL PROCEDURE                                        26                                     5.3EFFICIENCY                                                              27                                      5.4USAGE                                                                        27                                      5.

5 COST                                                                           27                                      5.6MANUFACTURERS                                                 28                       6.                                 CONCLUSION                                                                    29                                    REFERENCES                                                                    30