Shaun R. Patel, Joshua P. Aronson, Sameer A. Sheth, Emad N. Eskandar
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BRIEF HISTORY
The late eighteenth and nineteenth centu-ries witnessed the development of func-tional neuroanatomy—the concept thatspecific areas of the brain subserve particu-lar functions. Gall (19) ascribed functionalsignificance to individual units of the brainthat he called mental organs. His theory ofphrenology ultimately lost favor, but he wasnonetheless a pioneer of the concept of lo-calization of brain function. One of his de-tractors, Flourens (18), performed carefulexperiments that began to demonstrate thefunctions of the cerebral hemispheres, cer-ebellum, and brainstem. Broca (8) and Wer-
icke (70) further refined localization, es-ecially for language function.
This increasing understanding of func-ional neuroanatomy led the Swiss psychia-rist Burckhardt to postulate that removingegions of cortex could specifically alter be-
Key words� Major depression� Neurosurgery� Obsessive-compulsive disorder� Stereotactic� Surgery
Abbreviations and AcronymsBD: Bipolar disorderCGI: Clinical Global ImprovementCGPSS: Current Global Psychiatric Social StatusScaleCSTC: Corticostriatal-thalamocorticalDBS: Deep brain stimulationMDD: Major depressive disorderMRI: Magnetic resonance imagingOCD: Obsessive-compulsive disorderYBOCS: Yale-Brown Obsessive Compulsive Scale
Department of Neurosurgery, MassachusettsGeneral Hospital, Boston, Massachusetts, USA
To whom correspondence should be addressed:Dr. Emad N. Eskandar[E-mail: [email protected]]
Citation: World Neurosurg. (2013) 80, 3/4:S31.e9-S31.e16.http://dx.doi.org/10.1016/j.wneu.2012.11.038
atients with psychiatric diagnoses in 1888ikely represent the first modern example ofsychiatric neurosurgery. His results from
hese initial attempts were modest: one pa-ient died after developing status epilepti-us, one improved but then subsequentlyommitted suicide, two remained stable,nd two became more subdued.
In 1910, the Estonian neurosurgeonuusepp reported results on 17 patientsho underwent a frontal leukotomy-likerocedure for manic-depressive disorder orpilepsy (43). Results from the initial fouratients were poor; however, in the remain-
ng patients, improvement and reduced ag-ression were seen (57).
In 1935, Fulton presented a landmarktudy in primate neurophysiology thatould guide the direction of psychosur-ery for the next 2 decades. Fulton and
acobsen trained two chimpanzees to per-orm some basic behaviors. They notedhat under certain conditions when re-ard was omitted, the animals wouldave clear emotional tantrums. Each ani-al then underwent a unilateral frontal
obectomy. Fulton and Jacobsen noted
� OBJECTIVE: Lesion procedures for pspans more than a century. This reviesurgery and addresses the most rectreatment of anxiety and mood disord
� METHODS: Relevant data describehrough the modern era regarding lesioth historical and current use, are re
RESULTS: The early procedures ofviewed, followed by descriptions ofKnight, Foltz, White, and Kelly. The appcompulsive disorder, mood disorders,
� CONCLUSIONS: Lesioning procedustimulation targets. Recent lesioningdurability of these procedures in sevetion of these techniques should continusevere, refractory psychiatric disorder
hat there was no apparent change in their a
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verall cognitive or emotional capacities.owever, when the contralateral frontal
obe was also removed, they noticedarked changes in their emotional fac-
lty without any gross changes in overallognition. Specifically, they stopped re-ponding to the omission of rewards. Ful-on and Jacobsen presented their findingst the Second World Congress of Neurol-gy in 1935. At this meeting, the Portu-uese neurologist Moniz proposed abla-
ion of frontal cortex for treatment ofsychiatric disease in humans (25, 47).
Moniz enlisted the help of the Portu-uese neurosurgeon Lima. In 1935, theyerformed a prefrontal leukotomy on a3-year-old woman with anxiety, delu-ions, and melancholia. They injected al-ohol into white matter tracts within therontal lobes to sever connections respon-ible for the mental illness. The patientas considered to be cured, despite re-uiring continuous hospitalization (2).y 1936, Moniz and Lima introduced aew instrument called the leukotome,hich consisted of a rod that had a re-
ractable wire loop that could be inserted
hiatric indications have a history thatrovides a brief history of psychiatricliterature on lesion surgery for the
publications from the early 1900srocedures for psychiatric indications,ed.
khardt, Moniz, and Freeman are re-more refined techniques of Leksell,ion of lesion procedures to obsessive-addiction are discussed.
have informed modern deep braindies demonstrate the efficacy anddisabled patients. Judicious applica-r appropriately selected patients with
SHAUN R. PATEL ET AL. PSYCHIATRIC NEUROSURGICAL PROCEDURES
tions. The procedure was done bilaterallywith approximately six 10-mm circular le-sions per side. Over the next 2 years,Moniz published numerous articles andbooks on the procedure, and he won theNobel Prize in Medicine or Physiology in1949.
Concurrent to Moniz’s work, in 1936, theAmerican neurologist Freeman and neuro-surgeon Watts began exploring prefrontallobotomy as a treatment for psychiatric ill-ness. At the time, psychiatric illness was astaggering problem in the United States,with an estimated 400,000 psychiatric inpa-tients and an annual cost of $1.5 bil-lion (47). In an effort to make the proceduremore widely available, Freeman and Wattsintroduced the transorbital leukotomy in1946. The procedure did not require an op-erating room and was originally performedin Freeman’s office. An icepick-like tool,called an orbitoclast, was inserted above theeyelid and driven through the orbital roofwith a mallet. Sweeping motions weremade with the orbitoclast in the desiredplane to severe white matter tracts. The pro-cedure was done bilaterally. An estimated
Fig
60,000 procedures were performed from c
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936 –1956 (2). However, increasingly in-iscriminate use of the procedure, an accu-ulating tally of complications, and the de-
elopment of the first neuroleptics such ashlorpromazine eventually brought an endo the frontal lobotomy era (17).
The development of stereotactic proce-ures by Tailarach and Leksell in the late940s (42) allowed the creation of smaller,
ore precisely targeted lesions, resulting inmproved outcomes and reduced complica-ions. Stereotactic ablation procedures thatere developed over the next 2 decades are
till in use today to treat patients with severeisease that is refractory to conventionalharmacologic and behavioral therapy.odern practice of psychiatric neurosur-
ery must take careful account of ethicalbjections raised against the notorious
ransorbital frontal lobotomies of the mid-le decades of the 20th century. The ensu-
ng public backlash led to the convening ofU.S. Congressional Commission in the
ate 1970s to investigate the appropriate se-ection and treatment of patients for theserocedures. Their report formed the basis
or guidelines governing the practice of psy-
Timeline of major events in the history of psycho
hiatric neurosurgery (12, 69). U
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At the present time, psychiatric neuro-urgery procedures are most often per-ormed to treat severe, refractory anxietyisorders such as obsessive-compulsiveisorder (OCD) and mood disorders suchs bipolar disorder (BD) and major depres-ive disorder (MDD) (Table 1). We brieflyescribe these conditions and outline theblative procedures available to treat them.n addition, we discuss treatment of addic-ion, both historically and more recent in-ernational efforts.
BSESSIVE-COMPULSIVE DISORDER
escriptionCD is an anxiety disorder characterized byersistent unwanted thoughts (obsessions)nd ritualistic behaviors or mental actscompulsions). The intrusive nature of ob-essions is a source of overwhelming anxi-ty and often requires repetitive perfor-ance of time-consuming or socially
nappropriate behaviors to subdue. OCD isenerally considered to be a chronic illnessith a lifetime prevalence of 2%–3% in the
SHAUN R. PATEL ET AL. PSYCHIATRIC NEUROSURGICAL PROCEDURES
of care consists of cognitive behavioraltherapy and selective serotonin reuptake in-hibitors (28). Although meta-analytic stud-ies have shown both classes of treatment tobe effective (16, 40), 20%– 40% of patientsare thought to remain refractory and arechronically impaired (56, 58).
NeurobiologyThe pathophysiologic basis of OCD appearsto involve abnormalities in corticostriatal-thalamocortical (CSTC) circuits, specifi-cally orbital-frontal and anterior cingulatecortex (63, 68). CSTC circuits are known tobe anatomically and functionally segre-gated and subserve a wide range of physio-logic functions (1). Dysfunction to these in-formation streams is thought to underliethe neurobiologic basis of OCD (52).
Imaging studies have elucidated much ofwhat we know about the pathophysiologic ba-sis of OCD. Structural imaging studies havefound differences in gray matter volumes ofCSTC regions in patients with OCD versuscontrols (29, 61). Hyperactivity in CSTC cir-uits is commonly reported in patients withCD at rest in functional imaging studies,
nd this activity is amplified during provoca-ion of OCD symptoms (48, 59, 64). Diffusionensor imaging revealed abnormalities in an-tomic connectivity within the cingulum bun-le and the anterior limb of the internal cap-
mong the most common psychiatric diagno-es. During their lifetime, 20% of women and2% of men are expected to have a major de-ressive episode. BD is less common, with a
ifetime prevalence of 2%–4% (44). Conven-ional treatment at the present time consistsf psychopharmacology including selectiveerotonin reuptake inhibitors and mono-mine oxidase inhibitors, psychotherapy, andlectroconvulsive therapy. BD treatments in-lude mood stabilizers such as lithium, carba-azepine, and valproate. However, 20% of
atients are refractory to conventional ther-py. Ablative surgical procedures for depres-ion have been employed since the 1930s andefined by the advent of stereotaxy in the 1940snd 1950s (3).
eurobiologyhe pathophysiology underlying both MDDnd BD appears to involve abnormalities inedial and orbital prefrontal cortex, limbic
ircuits regulating emotion, and thalamic andasal ganglia networks (54). Dysregulation ofeurotransmitters, including serotonin andopamine, plays an important role as well.
Positron emission tomography and func-ional magnetic resonance imaging (MRI)
od Target S
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ive Compulsive Scale; MDD, major depressive disorder; BD,
tudies have demonstrated altered cerebral i
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lood flow and metabolic activity in prefron-al cortex of depressed patients comparedith healthy subjects. Primate studies suggest
hat the orbital prefrontal cortex plays a role inpdating the value of object representations,hereas medial frontal cortex updates the
alue of action representations. These rolesre reflected in difficulty valuing objects andctions, presenting clinically in patients withDD as anhedonia, abulia, and lack of moti-
ation (44, 54).
DDICTION
pidemiologic studies of substance abusend dependence reveal 2% of adults in U.S.ouseholds had a drug use disorder within
he previous 12 months, with 10.4% report-ng a drug use disorder during their lifetime65). Drug use disorders lead to significantisability and inability to fulfill work,chool, and home obligations. Currentreatment centers on residential or outpa-ient behavioral therapies combined withharmacologic therapies to manage with-rawal and control cravings. However, re-
apse rates remain exceedingly high despitereatment. A large randomized study ofombined behavioral and pharmacologicreatment for alcohol abuse demonstratedood clinical outcome, defined as absti-ence to moderate drinking without signif-
ffects Efficacy
che, confusion, OCD: 35% reduction in YBOCS
gain, fatigue,ntinence, seizure
effects, low risk OCD: 32%–48% reduction inYBOCS
MDD: 60% responders
BD: 77% improved
, disorientation OCD: 50% improved
MDD: 32% improved
che, confusion,ation,nolence, apathy,
OCD: 38%–98% improvement
MDD: 33% symptom-free,22% improved
BD: 68% improved by CGPSS
disorder; CGPSS, Current Global Psychiatric Social Status
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SHAUN R. PATEL ET AL. PSYCHIATRIC NEUROSURGICAL PROCEDURES
tients undergoing therapy, with loweroutcome rates for isolated behavioral orpharmacologic treatments (4). Interest inapplying psychiatric neurosurgery to sub-stance abuse was based on observations ofpatients with comorbid depression andsubstance abuse.
In 1969, Knight (38) reported his resultswith leucotomy in five heroin addicts, demon-strating reduced withdrawal symptoms andcravings and improved rehabilitation. No pa-tients relapsed in the 6-month follow-up pe-riod. In 1978, Dieckmann and Schneider(14) published their experience with hypo-thalamotomy for addiction. Leucotomy wasthought to influence addiction via treatmentof underlying mood disorders, and it was be-lieved that hypothalamotomy would directlyaffect relapse behaviors. Unilateral or bilaterallesioning of the ventromedial nucleus of thehypothalamus was performed in 15 patients.All patients reported increased self-controlbut also increased appetite and reduced sex-ual drive. In patients with bilateral lesions,four of six had severe side effects, includinglack of impulse, amnesia, vision disorders,and vegetative crisis. Bilateral hypothalamo-tomy was essentially abandoned.
Stereotactic anterior cingulotomy was eval-uated in the 1970s as a treatment of addiction.Kanaka and Balasubramaniam (31) reportedon 73 patients with morphine, pethidine, oralcohol addiction who underwent surgery.Patients were followed for up to 6 years, with arelapse rate of 22% without significant psy-chological deficits or procedural complica-tions. More recently, Russian neurosurgeonsreported results of cryocingulotomy in pa-tients with heroin addiction. Bilateral lesionswere created in 335 patients; 30% experi-enced immediate total remission, and an ad-ditional 30% were in remission after 2months. The follow-up period was unre-ported. However, the Russian government or-dered a halt to surgeries for lack of evidence in2002 (49, 55).
In 2003, Gao et al. (20) published resultsof ablating the nucleus accumbens bilater-ally. The goal was to disrupt the mesocorti-colimbic dopamine circuit, which was im-plicated in psychological dependence inanimal studies (35). Lesioning was per-ormed in 28 heroin addicts who were fol-owed for 15 months. Complete remission
as reported in 7 patients, and an addi-ional 10 patients relapsed within 6 months
ut did have an improvement in withdrawal t
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ymptoms. Two patients had personalityhanges, and four had temporary memoryoss. However, the study was severely lim-ted by poorly defined assessment instru-
ents, unblinded evaluators, and no com-arison with standard effective treatment
or opioid dependence. The Chinese gov-rnment halted surgeries in 2004 (45, 67).n 2010, Wu et al. (72) reported results oftereotactic ablation of the nucleus accum-ens in patients with alcohol dependence.ilateral lesioning was performed in 12 pa-
ients meeting criteria for alcohol depen-ence with repeated relapses despite treat-ent. Patients were followed for a mean of
6.6 months. Relapse rate by the first yearostoperatively was 25%. One patient had
emporary hyposmia; no other proceduralomplications were seen. Severity of alco-ol dependence and alcohol cravings, as de-
ermined by a standard severity of alcoholependence scale and frequency and dura-
ion of alcohol use, was decreased in thetudy group compared with preoperativeaseline. Given these encouraging results,
he authors suggested that stereotactic sur-ery to treat alcohol dependence is safe andffective, although greater sample size andonger follow-up studies would provide fur-her evidence of efficacy and safety. The au-hors commented that nondestructive pro-edures are likely to replace the lesioningsed in the study; however, the high cost of
mplanted stimulation devices may limitheir adoption (72).
ESIONING PROCEDURES
nterior Capsulotomyeveloped in the 1940s by Leksell and Ta-
airach, anterior capsulotomy targets thenterior limb of the internal capsule, justuperior to the ventral striatum (Figure 2)22). The goal of the procedure is to inter-upt fibers connecting the orbital frontalortex with thalamic nuclei and the caudate.riginally, bilateral lesions were placed us-
ng thermocoagulation through burr holesn the skull, resulting in roughly 4-mm-
ide lesions. More recently, capsulotomyas been performed using the Leksellamma Knife, stereotactically focusing
onizing radiation onto the target site. Al-hough it is a relatively new procedure, effi-acy is similar to thermocoagulation, and
he need for open surgery is eliminated. b
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controlled study of Gamma Knife capsu-otomy for OCD is currently in progress athe University of Sao Paulo, Brazil.
In the 1950s, Leksell performed anteriorapsulotomy on 116 patients and reportedavorable results; 50% improvement oc-urred in patients with OCD. More recentutcome studies of capsulotomy for intrac-
able OCD report an approximate 70% im-rovement (26, 41, 50). Short-term side ef-
ects include headache, confusion, andncontinence. Weight gain, fatigue, mem-ry loss, incontinence, and seizure haveeen reported as rare but more lasting sideffects (17). Therapeutic responses foramma Knife capsulotomy (�35% im-rovement in Yale-Brown Obsessive Com-ulsive Scale [YBOCS] at follow-up) haveeen reported in 60% of patients with OCD23), and no significant difference betweenhermocoagulation and radiosurgery haseen reported (62). Serious side effects ofadiosurgery include radiation-induceddema and delayed cyst formation (23).
nterior Cingulotomyhe earliest reports of cingulotomies date
Figure 2. Psychosurgical lesion targets. Forcingulotomy, two of three magneticresonance imaging–guided lesions are placedbilaterally in the anterior cingulate (red) usingthermocoagulation to interrupt fibers fromthe cingulate to the limbic system. Forcapsulotomy, bilateral lesions are placed inthe anterior limb of the internal capsule (blue)using either thermocoagulation or ionizingradiation to interrupt fibers from the orbitalfrontal cortex to thalamic and basal gangliatargets. For subcaudate tractotomy, bilaterallesions are placed in the substantiainnominata (green; inferior to the head of thecaudate) using radioactive rods to interruptfibers between the orbital frontal cortex andsubcortical limbic targets. For limbicleukotomy, anterior cingulotomy (red) andsubcaudate tractotomy (green) lesion targetsare combined.
SHAUN R. PATEL ET AL. PSYCHIATRIC NEUROSURGICAL PROCEDURES
was noted that patients with comorbid anx-iety conditions had the best outcomes.Cairns began targeting the anterior cingu-lum in 1948 for anxiety, intractable pain,and mood disorders. At the present time,anterior cingulotomy remains the mostcommon neurosurgical procedure for re-fractory OCD.
The anterior cingulate gyrus has projec-tions into hippocampus, amygdala, periaq-ueductal gray matter, ventral striatum, andorbitofrontal and anterior insular cortices.Functionally, it is involved in conditionedemotional learning and assigning emo-tional valence to stimuli (13). Two or threeMRI-guided lesions of approximately 1.0cm3 are made bilaterally in the anterior cin-
ulate (Brodmann areas 24 and 32) by ther-ocoagulation (Figure 2). The goal of this
rocedure is to interrupt fiber tracts in thenterior cingulate that carry informationrom the cingulate cortex to the orbital fron-al cortex and limbic system.
Ballantine published results of 69 pa-ients who underwent bilateral stereotacticingulotomy during 1962–1966. Lesionsere created using monopolar radiofre-uency electrocoagulation with needleslaced 3– 4 cm from the tip of frontal horns
o within 5 mm of the midline to destroy theedial portion of the cingulum. Of pa-
ients, 26 had manic-depressive symptomsonsistent with a modern diagnosis of BD.n 20 patients (77%), significant improve-
ent occurred as a result of surgery; these0 patients were followed for 3 months upo 4 years. There were no deaths or majoromplications attributed to surgery, al-hough three patients (4%) experiencedostoperative seizures (6).
In 1987, the safety and efficacy of anterioringulotomies for a range of psychiatricisorders were first characterized (5). Us-
ng a subjective functional/symptomaticating scale, a 56% improvement for pa-ients with OCD was reported. In 2000,osgrove (11) reanalyzed these data with
more rigid criteria and found a 33% im-provement from cingulotomies.
MRI-guided cingulotomy results fromMassachusetts General Hospital from1991–1995 were reported by Spangler et al.in 1996 (66). Patients were followed for
–38 months (mean 17 months), and out-ome was assessed via the Clinical Globalmprovement (CGI) scale and the Current
lobal Psychiatric Social Status Scale t
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CGPSS). Patients were considered re-ponders if they improved on the CGIcale and were no longer institutionalizednd usually working to some extent (CG-SS score �3). Partial responders wereinimally improved or better on the CGI
cale or showed at least some improvementhile still requiring intensive care or insti-
utionalization on CGPSS (score �2). Of 34atients in the series, 10 had MDD, and 5ad BD. Of the patients with MDD, 60%ere characterized as responders, 10%ere characterized as possible responders,
nd 30% were characterized as nonre-ponders. Of the five patients with BD, two40%) were responders, two (40%) wereossible responders, and one (20%) was aonresponder. The authors stated cingu-
otomy is associated with mild, transientide effects and reported no major long-erm complications (66).
More recently, long-term prospectivetudies found a 32%– 48% reduction inaseline YBOCS scores after cingulotomies15, 30). Cingulotomies have a relatively lowate of side effects. A report on the safety of
800 cingulotomies performed at the Mas-achusetts General Hospital over a 40-yeareriod showed no deaths and only two in-
ections (12).
ubcaudate Tractotomyubcaudate tractotomies were first per-ormed by Knight in 1964 (37). The ratio-ale was to interrupt white matter tractsonnecting the orbital frontal cortex andubcortical limbic structures by targetinghe substantia innominata (just inferior tohe head of the caudate nucleus) (Figure 2)36). Knight focused on the last 2 cm of theesion created by orbital undercutting,
here it entered the subcaudate region.his selective cortical undercutting led to
mproved results (37), although freehandrocedures often led to suboptimal lesion
ocalization. The addition of stereotaxy en-bled standardized lesion localization andas termed stereotactic subcaudate tractot-my. Knight used McCaul’s stereotactic de-ice to insert rods of radioactive yttrium-90ilaterally into the white matter just belownd anterior to the caudate. �-radiationmitted from the rods destroyed white mat-er 2 mm from the surface of the rod. A
ore recent revision to this procedure re-laces yttrium-90 rods with thermocon-
rolled high-frequency electrocoagulation,
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ith lesions stereotactically created via Lek-ell frame localization in a manner mimick-ng the size and location of lesions createdy the yttrium-90 rods.
In 1975, Goktepe et al. (21) reported on208 patients with a mean follow-up periodof 2.5 years; using a categorical outcomescale, they found a 50% improvement inpatients with OCD after subcaudate tracto-tomies. Since 1970, the Brook General Hos-pital in London has performed �1300 sub-caudate tractotomies for affective disorders(unipolar or bipolar), OCD, and chronicanxiety (7). Using global clinical categoricaland symptom rating scales, they reported40%– 60% of patients led normal or near-normal lives after 1-year postsurgical as-sessments. Similar to cingulotomies, sub-caudate tractotomies are relatively free ofmajor complications. Edema-induced dis-orientation is observed in approximately10% of patients postoperatively and maylast 1 month. Seizures are the most com-mon long-term complication and are seenin only about 1.6% of patients. Knight (39)reported only one death from �1300 casesexamined. More recently, there has been acase report of one patient with OCD im-proving after a frameless stereotactic sub-caudate tractotomy (71).
Hodgkiss et al. (27) reported results ofstereotactic subcaudate tractotomy in 286patients treated from 1979 –1991 at theGeoffrey Knight National Unit for AffectiveDisorders in London. Diagnostic and fol-low-up data were available on 249 patients;183 of these patients had a diagnosis of de-pression. Outcome was assessed 12 monthsafter surgery and categorized as recovered(no symptoms, no additional treatment),well (mild residual symptoms, little to nointerference with everyday life, may requiremedication), improved (significant residualsymptoms), unchanged, and worse. For pa-tients with depression, 64 (34%) were re-covered or well, 58 (32%) were improved,and 57 (31%) were unchanged or worse.The study did not disclose detailed compli-cations; however, five patients (3%) in thedepression group died within the 12-monthfollow-up period.
Limbic LeukotomyIn 1973, Kelly et al. (33) reported a novelstereotactic surgical approach focusing ondiscrete lesions disrupting connections to
the limbic system. Targets included the
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SHAUN R. PATEL ET AL. PSYCHIATRIC NEUROSURGICAL PROCEDURES
lower medial quadrant of the frontal lobe tointerrupt frontolimbic connections and thecingulum bundle running above the corpuscallosum to interrupt the Papez circuit (Fig-ure 2). Lesions around 8 mm in size wereproduced with wire loops, blunt instru-ments, heat, or radioactive materials. Post-operatively, patients were confused anddrowsy for the initial 24 – 48 hours and thenslowly recovered and returned to psychiat-ric care.
Kelly et al. (33) assessed 66 patients in1973 with a mean follow-up of 16 monthsafter surgery; using a 5-point clinical ratingscale, they reported an 89% improvement inpatients with OCD. In 1993, Hay et al. (24)reported an improvement in 38% of their 26patients after surgery. In 2002, Kim et al.(34) reported a decrease in mean YBOCSscores from 34 to 3 in 12 patients who un-derwent limbic leukotomy for OCD; at 45months after surgeon, 10 of the 12 patientsreturned to previously normal state of func-tion. In 2008, Cho et al. (10) reported a7-year study of 18 patients who underwentlimbic leukotomy for intractable affectivedisorders. They reported significant im-provements according to rating scales indepression (Hamilton Depression RatingScale), anxiety (Hamilton Anxiety RatingScale), and negative symptoms (NegativeSymptom Rating Scale). Short-term side ef-fects included headache, confusion, leth-argy, and perseveration (23).
Mitchell-Heggs et al. (51) reported theirresults of 66 patients followed for 16months postoperatively. There were ninepatients with depression, all of whom wereimproved at 6 weeks; however, at 16months, three (33%) were symptom-free,two (22%) had minimal residual symp-toms, two (22%) were improved with sig-nificant residual symptoms, and two (22%)were unchanged. The authors commentedon 100 patients who underwent the proce-dure as of publication date and reportedonly one serious complication, postopera-tive memory deficit. Transient confusion,headache, incontinence, and lethargy re-solved within a few weeks of surgery.
Montoya et al. (53) reported results of 21atients who underwent MRI-guided ste-eotactic limbic leukotomy at Massachu-etts General Hospital from 1993–1999.ean follow-up time was 26 months. Six
atients (29%) were diagnosed with refrac-
ory depression. Four patients had previ- p
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usly undergone bilateral anterior cingu-otomy as well as a second surgery toxpand these lesions. Lesions were createdith radiofrequency thermoablation. Tar-ets were just inferior to the head of theaudate nucleus and the anterior cingulateyrus, approximately 2 cm posterior to
he tips of the frontal horns. Three patients50%) were considered responders to sur-ery according to physician-rated assess-ents of global functioning. One patient
ommitted suicide postoperatively. Among1 patients, complications included wound
nfection in 1 patient, persistent complexartial seizures in 1 patient, short-termemory disorder in 2 patients, and persis-
ent headaches in 1 patient; minor transientostoperative symptoms included somno-
Limbic leukotomy performed to treat BDn 16 patients in Taiwan was reported. Ra-iofrequency thermocoagulation was car-ied out during 1997–1998, and patientsere followed for 7 years. Outcome was as-
essed with CGPSS. Additional psychiatricests administered included Hamilton De-ression Rating Scale, Young Depressionating Scale, Beck Depression Inventorycale, Hamilton Anxiety Rating Scale,oung Mania Rating Scale, Brief Psychiatricating Scale, Active Symptom Scale, andegative Symptom Scale. Tests were ad-inistered annually for 7 years. Of patients,
8.8% had a marked response (CGPSScore �3, improved and usually working,r better), 18.8% had a possible responseCGPSS score 2), and 12.6% did not im-rove or declined. Evaluating the entire bat-
ery of outcome scales revealed significantmprovement in depressive, anxiety, andegative symptoms, with no significanthange in mania and active symptoms.hree patients experienced minor compli-ations of local infection, transient halluci-ations, and extrapyramidal symptoms
10).
ONCLUSIONS
wo important conclusions can be drawnrom the history and modern outcomes ofblative neurosurgical procedures for psy-hiatric conditions. First, it is imperative todhere to carefully considered guidelinesn the ethical selection of patients for these
rocedures. A multidisciplinary team of
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sychiatrists, neurologists, and neurosur-eons should assess candidacy thoroughlyefore offering surgery. There are no estab-
ished criteria governing how to determineandidacy for either lesioning or deep braintimulation (DBS) or how to distinguish be-ween the two. For the former, institutionshat offer these procedures have typicallystablished their own criteria, which usu-lly include refractoriness to conventionalharmacologic and behavioral therapy and
ack of psychotic or Axis II features. ForBS, at the present time, a substantial frac-
ion of procedures are done within the stip-lations of a clinical trial. Inclusion and ex-lusion criteria tend to be quite similaretween lesioning and DBS procedures. Inur opinion, the consensus reached in the
ate 1970s by the Congressional Commis-ion (60) provides an excellent framework
by which to determine eligibility for psychi-atric surgery.
Second, more recent lesioning studiescontinue to demonstrate the efficacy anddurability of outcomes in these severely dis-abled patients. It will be important to com-pare the outcomes of emerging neurosurgi-cal techniques such as DBS with theoutcomes accumulated over decades withlesions. The judicious application of lesion-ing techniques should continue to be con-sidered for appropriately selected patientswith severe, refractory psychiatric disor-ders.
REFERENCES
1. Alexander GE, Crutcher MD: Functional architec-ture of basal ganglia circuits: neural substrates ofparallel processing. Trends Neurosci 13:266-271,1990.
2. Anderson CA, Arciniegas DB: Neurosurgical inter-ventions for neuropsychiatric syndromes. Curr Psy-chiatry Rep 6:355-363, 2004.
3. Andrade P, Noblesse LHM, Temel Y, Ackermans L,Lim LW, Steinbusch HWM, Visser-Vandewalle V:Neurostimulatory and ablative treatment options inmajor depressive disorder: a systematic review. ActaNeurochir 152:565-577, 2010.
4. Anton RE, O’Malley SS, Ciraulo DA, Cisler RA,Couper D, Donovan DM, Gastfriend DR, HoskingJD, Johnson BA, LoCastro JS, Longabaugh R, MasonBJ, Mattson ME, Miller WR, Pettinati HM, RandallCL, Swift R, Weiss RD, Williams LD, Zweben A:COMBINE Study Research GroupCombined phar-macotherapies and behavioral interventions for al-
cohol dependence: the COMBINE study: a random-ized controlled trial. JAMA 295:2003-2017, 2006.
8. Broca P: Note on the seat of the faculty of articulatedlanguage, followed by an observation of loss ofspeech [in French]. Bulletin de la SocieteAnatomique de Paris; 1861.
9. Cannistraro PA, Makris N, Howard JD, Wedig MM,Hodge SM, Wilhelm S, Kennedy DN, Rauch SL:A diffusion tensor imaging study of white matter inobsessive-compulsive disorder. Depress Anxiety 24:440-446, 2007.
0. Cho DY, Lee WY, Chen CC: Limbic leukotomy forintractable major affective disorders: a 7-year fol-low-up study using nine comprehensive psychiatrictest evaluations. J Clin Neurosci 15:138-142, 2008.
1. Cosgrove GR: Surgery for psychiatric disorders.CNS Spectr 5:43-52, 2000.
2. Cosgrove GR, Rauch SL: Stereotactic cingulotomy.Neurosurg Clin N Am 14:225-235, 2003.
3. Devinsky O, Morrell MJ, Vogt BA: Contributions ofanterior cingulate cortex to behaviour. Brain 118:279-306, 1995.
4. Dieckmann G, Schneider H: Influence of stereotac-tic hypothalamotomy on alcohol and drug addic-tion. Appl Neurophysiol 41:93-98, 1978.
5. Dougherty DD, Baer L, Cosgrove GR, Cassem EH,Price BH, Nierenberg AA, Jenike MA, Rauch SL:Prospective long-term follow-up of 44 patientswho received cingulotomy for treatment-refrac-tory obsessive-compulsive disorder. Am J Psychi-atry 159:269-275, 2002.
6. Eddy KT, Dutra L, Bradley R, Westen D: A multidi-mensional meta-analysis of psychotherapy andpharmacotherapy for obsessive-compulsive disor-der. Clin Psychol Rev 24:1011-1030, 2004.
8. Flourens P: Experimental research on the propertiesand functions of the nervous system in vertebrateanimals [in French]. Balliere; 1842.
9. Gall FJ: The anatomy and physiology of the nervoussystem in general and of the brain in particular: themorals and dispositions of man and animal can beinferred from the external appearances of the skull[in French]. F. Schoell; 1818.
0. Gao G, Wang X, He S, Li W, Wang Q, Liang Q, ZhaoY, Hou F, Chen L, Li A: Clinical study for alleviating
opiate drug psychological dependence by a methodof ablating the nucleus accumbens with stereotactic
1. Goktepe EO, Young LB, Bridges PK: A further reviewof the results of stereotactic subcaudate tractotomy.Br J Psychiatry 126:270-280, 1975.
2. Greenberg BD, Price LH, Rauch SL, Friehs G, NorenG, Malone D, Carpenter LL, Rezai AR, RasmussenSA: Neurosurgery for intractable obsessive-com-pulsive disorder and depression: critical issues.Neurosurg Clin N Am 14:199-212, 2003.
3. Greenberg BD, Rauch SL, Haber SN: Invasive cir-cuitry-based neurotherapeutics: stereotactic abla-tion and deep brain stimulation for OCD. Neuropsy-chopharmacology 35:317-336, 2009.
4. Hay P, Sachdev P, Cumming S, Smith JS, Lee T,Kitchener P, Matheson J: Treatment of obsessive-compulsive disorder by psychosurgery. Acta Psychi-atr Scand 87:197-207, 1993.
5. Heller AC, Amar AP, Liu CY, Apuzzo MLJ: Surgery ofthe mind and mood: a mosaic of issues in time andevolution. Neurosurgery 62 (6 Suppl 3):921-940,2008.
6. Herner T: Treatment of mental disorders with fron-tal stereotaxic thermo-lesions: a follow-up study of116 cases. Acta Psychiatry Scad 36 (Suppl):941-967,1961.
7. Hodgkiss AD, Malizia AL, Bartlett JR, Bridges PK:Outcome after the psychosurgical operation of ste-reotactic subcaudate tractotomy, 1979-1991. J Neu-ropsychiatr Clin Neurosci 7:230-234, 1995.
8. Husted DS, Shapira NA: A review of the treatmentfor refractory obsessive-compulsive disorder: frommedicine to deep brain stimulation. CNS Spect9:833-847, 2004.
0. Jung HH, Kim CH, Chang JH, Park YG, Chung SS,Chang JW: Bilateral anterior cingulotomy for refrac-tory obsessive-compulsive disorder: long-term fol-low-up results. Stereotact Funct Neurosurg 84:184-189, 2006.
1. Kanaka TS, Balasubramaniam V: Stereotactic cingu-lumotomy for drug addiction. Appl Neurophysiol41:86-92, 1978.
2. Karno M, Golding JM, Sorenson SB, Burnam MA:The epidemiology of obsessive-compulsive disor-der in five US communities. Arch Gen Psychiatry45:1094-1099, 1988.
3. Kelly D, Richardson N, Mitchell-Heggs N, GreenupJ, Chen C, Hafner RJ: Stereotactic limbic leucotomy:a preliminary report on forty patients. Br J Psychiatry123:141-148, 1973.
4. Kim MC, Lee TK, Choi CR: Review of long-term
results of stereotactic psychosurgery. Neurol MedChir 42:365-371, 2002.
5
9-S31.e16, SEPTEMBER/OCTOBER 2013www.WOR
5. Kiyatkin EA: Dopamine in the nucleus accumbens:cellular actions, drug- and behavior-associated fluc-tuations, and a possible role in an organism’s adap-tive activity. Behav Brain Res 137:27-46, 2002.
6. Knight G: 330 cases of restricted orbital cortex un-dercutting. P Roy Soc Med 53:728-732, 1960.
7. Knight G: Stereotactic tractotomy in the surgicaltreatment of mental illness. J Neurol NeurosurgPsychiatry 28:304-310, 1965.
8. Knight G: Chronic depression and drug addictiontreated by stereotactic surgery. Nursing Times 65:583-586, 1969.
9. Knight G: Further observations from an experienceof 660 cases of stereotactic tractotomy. PostgradMed J 49:845-854, 1973.
0. Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ,Henk HJ: Behavioral versus pharmacological treat-ments of obsessive compulsive disorder: a meta-analysis. Psychopharmacology 136:205-216, 1998.
1. Leiphart JW, Valone FH: Stereotactic lesions for thetreatment of psychiatric disorders. J Neurosurg 113:1204-1211, 2010.
2. Leksell L: A stereotaxic apparatus for intracerebralsurgery. Acta Chir Scand 99:229-233, 1949.
3. Lichterman BL: On the history of psychosurgery inRussia. Acta Neurochir 125:1-4, 1993.
5. Lu L, Wang X, Kosten TR: Stereotactic neurosurgi-cal treatment of drug addiction. Am J Drug AlcoholAbuse 35:391-393, 2009.
6. Manjila S, Rengachary S, Xavier AR, Parker B,Guthikonda M: Modern psychosurgery before EgasMoniz: a tribute to Gottlieb Burckhardt. NeurosurgFocus 25:E9, 2008.
7. Mashour GA, Walker EE, Martuza RL: Psychosur-gery: past, present, and future. Brain Res Rev 48:409-419, 2005.
8. McGuire PK, Bench CJ, Frith CD, Marks IM, Frack-owiak RS, Dolan RJ: Functional anatomy of obses-sive-compulsive phenomena. Br J Psychiatry 164:459-468, 1994.
9. Medvedev SV, Anichkov AD, Poliakov LL: Physio-logical mechanisms of the effectiveness of bilat-eral stereotactic cingulotomy in treatment ofstrong psychological dependence in drug addic-tion. Fiziologiia Cheloveka 29:117-123, 2003.
0. National Commission for the Protection of HumanSubjects of Biomedical and Behavioral Research:
Psychosurgery. Washington, D.C.: U.S. Depart-ment of Health, Education, and Welfare; 1977.
S31.e16 www.SCIENCEDIRECT.com
1. Robinson D, Wu H, Murine RA, Ashtari M, Alvir JM,Lerner G, Koreen A, Cole K, Bogerts B: Reducedcaudate nucleus volume in obsessive-compulsivedisorder. Arch Gen Psychiatry 52:393-398, 1995.
2. Rtick C, Karlsson A, Steele JD, Edman G, MeyersonBA, Ericson K, Nyman H, Asberg M, Svanborg P:Capsulotomy for obsessive-compulsive disorder:long-term follow-up of 25 patients. Arch Gen Psy-chiatry 65:914-921, 2008.
3. Saxena S, Brody AL, Maidment KM, Dunkin JJ, Col-gan M, Alborzian S, Phelps ME, Baxter LR: Local-ized orbitofrontal and subcortical metabolicchanges and predictors of response to paroxetinetreatment in obsessive-compulsive disorder. Neu-ropsychopharmacology 21:683-693, 1999.
4. Saxena S, Rauch SL: Functional neuroimaging andthe neuroanatomy of obsessive-compulsive disor-der. Psychiatr Clin N Am 23:563-586, 2000.
5. Schulden JD, Thomas YF: Substance abuse in theUnited States: findings from recent epidemiologicstudies. Curr Psychiatr Rep 11:353-359, 2009.
7. Stelten BM, Noblesse LH, Ackermans L, Temel Y,Visser-Vandewalle V: The neurosurgical treatmentof addiction. Neurosurg Focus 25:E5, 2008.
8. Szeszko PR, MacMillan S, McMeniman M, Chen S,Baribault K, Lim KO, Ivey J, Rose M, Banerjee SP,Bhandari R, Moore GJ, Rosenberg DR: Brain struc-tural abnormalities in psychotropic drug-naive pe-
diatric patients with obsessive-compulsive disor-der. Am J Psychiatry 161:1049-1056, 2004.
1A
WORLD NEUROSURGERY, http://d
9. U.S. Department of Health, Education, and Wel-fare: Protection of human subjects. Use of psycho-surgery in practice and research: report and recom-mendations of National Commission for theProtection of Human Subjects. Fed Reg 42:26318-26332, 1977.
0. Wernicke C: The aphasic symptom complex: a psy-chological study on an anatomical basis [in Ger-man]. Cohn & Weigert; 1874.
1. Woerdeman PA, Willems PWA, Noordmans HJ,Berkelbach van der Sprenkel JW, van Rijen PC: Fra-meless stereotactic subcaudate tractotomy for in-tractable obsessive-compulsive disorder. Acta Neu-rochir 148:633-637, 2006.
2. Wu HM, Wang XL, Chang CW, Li N, Gao L, Geng N,Ma JH, Zhao W, Gao GD: Preliminary findings inablating the nucleus accumbens using stereotacticsurgery for alleviating psychological dependence onalcohol. Neurosci Lett 473:77-81, 2010.
onflict of interest statement: The authors declare that therticle content was composed in the absence of anyommercial or financial relationships that could beonstrued as a potential conflict of interest.
eceived 5 March 2012; accepted 9 November 2012;ublished online 14 November 2012
itation: World Neurosurg. (2013) 80, 3/4:S31.e9-S31.e16.ttp://dx.doi.org/10.1016/j.wneu.2012.11.038
