Journal of Clinical Neuroscience 18 (2011) 1210–1214

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Journal of Clinical Neuroscience

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Clinical Study

A single institution series of cavernomas of the brainstem

Girish Menon, C.V. Gopalakrishnan ⇑, B.R.M. Rao, Suresh Nair, Jayanand Sudhir, Mridul SharmaDepartment of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India

a r t i c l e i n f o a b s t r a c t

Article history:Received 10 December 2010Accepted 7 January 2011

Keywords:BrainstemCavernomaManagementOperative indicationOutcome

0967-5868/$ - see front matter � 2011 Elsevier Ltd. Adoi:10.1016/j.jocn.2011.01.022

⇑ Corresponding author. Tel.: +91 471 2524647; faxE-mail address: doc_gopal@yahoo.com (C.V. Gopal

We retrospectively analyzed a series of patients with brainstem cavernomas of the medulla, pons, or mid-brain to attempt to define the natural history, indications for surgery, and outcome after surgical resec-tion. Between 1993 and 2008, 52 patients with cavernomas of the brainstem presented to our instituteand were managed either surgically or conservatively. Twenty-three patients underwent surgical exci-sion using standard skull base approaches. Outcomes were correlated to the number of preoperativehemorrhages, location of the cavernoma, timing of surgery in relation to the hemorrhage and the preop-erative neurological status. Nine patients improved after surgery, 12 deteriorated and two died. In theconservatively managed group, 15 patients had a good outcome, 11 deteriorated and one died. Multiplehemorrhages, poor preoperative neurological status and surgery during the acute phase were predictiveof the surgical outcome. Excision of brainstem cavernomas should be considered in patients with symp-tomatic hemorrhages whose lesions approach the pial surface. Patients with minimal stable neurologicdeficits without recurrent bleeds should be managed conservatively.

� 2011 Elsevier Ltd. All rights reserved.

1. Introduction

Approximately 10% to 30% of intracranial cavernomas occur inthe posterior fossa. Brainstem cavernomas are rare and compriseless than 20% of intracerebral cavernomas.1–3 Approximately 57%of cavernomas occur in the pons, followed by the midbrain (14%),pontomedullary junction (12%), and medulla (5%).4 The natural his-tory of brainstem cavernomas remains poorly understood and cur-rent management guidelines lack consensus. The rebleed rate forpatients with brainstem cavernomas has been reported to be ashigh as 30% per person per year.5 Mortality rates of up to 20% havebeen reported for patients managed conservatively,6 whereas mor-tality rates following surgery range from 0 to 1.9%.7–9 However,resection is technically demanding and is associated with the riskof additional brainstem injury. We retrospectively analyzed 52 pa-tients who were managed either surgically or conservatively at ourinstitution and compared their long-term outcomes with similarpublished series.

2. Materials and methods

The study period spanned 15 years, from 1993 to 2008. Fifty-twopatients with brainstem cavernomas were identified retrospectivelyby reviewing outpatient and hospital charts. All patients included inthe study had a cavernoma in their brainstem identified by imaging,

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: +91 471 2550728.akrishnan).

irrespective of the presence of a cavernoma elsewhere in the centralnervous system (CNS). Twenty-three patients were surgically trea-ted and 29 were conservatively managed. We analyzed patientdemographic data, their clinical status using the modified RankinScale score (mRS), cavernoma characteristics, surgical procedures,and the outcome on follow-up. All patients initially presented withone of the following: (i) one or more episodes of hemorrhage; (ii) aneurological deficit without any hemorrhage; or (iii) an incidentallesion on imaging. The latter group also included patients who hadhemorrhages from cavernomas in other anatomical locations. Thepatients’ clinical status at the time of admission and their outcomewas measured using the mRS recorded in their charts. The outcomewas considered ‘‘good’’ if there was an improvement in the mRS by atleast one point, ‘‘stable’’ if the mRS remained the same, and ‘‘poor’’ ifthe mRS deteriorated. The following parameters were analyzed foroutcome: (i) number of preoperative hemorrhages; (ii) location ofthe cavernoma; (iii) timing of surgery in relation to the hemorrhage;and (iv) the preoperative neurological status. Statistical analysis wasperformed using the Statistical Package for the Social Sciences forWindows, version 13.0 (SPSS, Chicago, IL, USA). The level of signifi-cance was set at 0.05.

3. Results

3.1. Demographics

There were 29 male and 23 female patients (male:female ra-tio = 1.26:1). The mean age at initial presentation was 25.4 years

G. Menon et al. / Journal of Clinical Neuroscience 18 (2011) 1210–1214 1211

(range = 11–58). Eight patients had multiple cavernomas (caverno-mas in other locations beyond the brainstem); two of these pa-tients were in the surgical group.

3.2. Presentation

The majority (76.9%) of patients presented with hemorrhageand related sequelae, 17.4% presented with a neurological deficitalone and 5.7% were diagnosed incidentally. The symptoms at pre-sentation are listed in Table 1. The most common clinical presenta-tion was a single or combined cranial nerve deficit (94.2%),followed by hemiparesis (48.1%) and hemisensory loss (23.1%).None of our patients were presented in a coma. Other symptomsat presentation were headache, ataxia, vertigo and tremor. At thetime of admission, 40 patients had an mRS of 6 2 and the remain-der had a score of 3, 4 or 5.

3.3. Anatomical location

Brainstem cavernomas were divided into five groups based ontheir location: (i) Group I: cavernomas within the midbrain, 12 pa-tients (23.1%); (ii) Group II: cavernomas within the pons, 22 pa-tients (42.3%); (iii) Group III: pontomesencephalic cavernomas,six patients (11.5%); (iv) Group IV: pontomedullary cavernomas,nine patients (17.3%); and (v) Group V: cavernomas within the me-dulla, three patients (5.8%). Two patients had a venous angioma inthe cerebellum which was detected by imaging.

3.4. Rebleeding

In the surgical group, five (21.7%) patients had a history of a sin-gle episode of hemorrhage, while 18 (78.3%) patients had evidenceof multiple hemorrhages. Of the 29 patients in the conservativearm, 11 (37.9%) had a single hemorrhage and the remaining 18(62.1%) had a history suggestive of multiple hemorrhages. Multiplehemorrhages were more frequent in patients with pontomesence-phalic cavernomas than in patients with cavernomas of the pons ormedulla; however, the difference was not significant. Every in-stance of rebleeding was associated with a new neurological defi-cit. Of 16 patients who had a single episode of hemorrhage, fewercranial nerve deficits (65.0%) were evident on examination com-pared to patients with multiple hemorrhages (81.2%). While six pa-tients underwent surgery within 3 weeks of the hemorrhage, 10underwent surgery within 3 months and seven underwent surgery3 months after the last ictus.

3.5. Surgical methods

Twenty-three patients (44.2%) in this study underwent surgery.A cavernoma was considered for surgical resection if it abutted thepial surface or was exophytic, and there was history of either mul-tiple hemorrhages or the patient had progressive neurological def-

Table 1Symptoms and clinical signs of patients (n = 52) on presentation with brainstemcavernomas of the medulla, pons, or midbrain

Symptom No. of patients Percentage

Cranial nerve palsy 49 94.2Hemiparesis 25 48.1Hemianesthaesia 12 23.1Headache 11 21.2Ataxia 10 19.2Dysphasia 9 17.3Vertigo 5 9.6Tremor 1 1.9Altered sensorium 1 1.9

icits. The goals of surgery were to achieve complete extirpation ofthe lesion to prevent rebleeding, to minimize damage to the sur-rounding normal brainstem parenchyma, and to preserve associ-ated venous anomalies. No attempt was made to removehemosiderin-stained tissue. The diagnosis of all resected lesionswere confirmed by histological examination. The standard mediansuboccipital or a lateral suboccipital presigmoid approach wasused in 17 patients. Of the patients with lesions involving the mid-brain, a subtemporal approach was used in five patients and anoccipital transtentorial approach was used in one patient. Brain-stem entry was guided by the presence of color change (red-brown) at the surface of the brainstem which was visible in allbut seven patients. A small myelotomy was required in the otherpatients. While the hemosiderin rim provided a good plane ofcleavage in the majority of patients, a poor plane for dissectionwas noted in all the patients who underwent surgery in the acutephase. Not surprisingly, these patients also had a poor outcome.

3.6. Postoperative deficits

Eleven (47.8%) surgical patients developed new neurologicaldeficits, including six patients who experienced deterioration inlimb power, and five patients who developed new cranial nervedeficits. None of these patients improved during follow-up. Pa-tients with pontine and midbrain cavernomas, or those who hada history of recurrent hemorrhages, had an increased probabilityof developing postoperative deficits; the latter group’s probabilitywas statistically significant (p = 0.03). Only six patients had resolu-tion of preoperative cranial nerve deficits at long-term follow-up.In terms of the preoperative time interval between the last hemor-rhage and surgery, and its relationship to postoperative outcome,analysis revealed that patients who underwent surgery in theacute phase were more likely to have new postoperative deficits.

3.7. Complications and mortality

Two postoperative deaths were attributable to surgery. Threepatients required a temporary tracheostomy in the postoperativeperiod for pulmonary toilet. Two patients had a complicated post-operative course and required a tracheostomy, prolonged ventila-tion and nasogastric feeding; both patients were completelydependent for activities of daily living at long-term follow-up.

3.8. Follow-up

We obtained follow-up data for 50 patients (96.2%). The meanfollow-up period was 42 months for the surgical group and48 months for the conservatively managed group. In the surgicalgroup, two patients died in the postoperative period. Nine(42.8%) patients had a good outcome as measured by an improve-ment in the mRS. Six (28.6%) patients remained stable. Six (28.6%)patients had a poor outcome as measured by a fall in the mRS(Table 2). In the conservative group, two patients were lost to fol-low-up and one died after an episode of recurrent hemorrhage.Five patients had an episode of single hemorrhage within 2 yearsbut remained clinically stable without any deterioration in theirmRS. Twelve (44.4%) patients in this group had more than two epi-sodes of clinical and radiologically evident hemorrhage during fol-low-up and all had a deterioration in their mRS.

Overall, 14 (51.8%) patients had a good outcome as measured bya stable or improved mRS (Table 3). Patients with recurrent hem-orrhages and a poor preoperative neurological status fared poorlyin both the surgical and conservative groups (p = 0.02 andp = 0.03, respectively). The likelihood of these patients developingnew neurological deficits was higher.

Table 2Modified Rankin Scale for the surgical group with brainstem cavernomas (n = 23)

mRS At admission At last follow-up

62 15 Improved/same 15Worse 0

3–5 8 Improved/same 0Worse 6�

� Two patients died after surgery. mRS = modified Rankin Scale.

Table 3Modified Rankin Scale for the conservatively managed group with brainstemcavernomas (n = 29)

mRS At admission At last follow-up

62 20� Improved/same 13Worse 5

3–5 9 Improved/same 1Worse 7�

� Two patients were lost to follow-up.� One patient died due to a recurrent hemorrhage. mRS = modified Rankin Scale.

1212 G. Menon et al. / Journal of Clinical Neuroscience 18 (2011) 1210–1214

4. Discussion

Management of brainstem cavernomas is a matter of consider-able debate and controversy. The first surgery for brainstem caver-noma was reported by Dandy in 1928 and the patient apparentlyrecovered well.10 In 2003 Wang et al. reported the largest surgicalseries of 137 patients from a single institution.11 Despite these re-ports, contentious issues regarding management of cavernomas in-clude: (i) the natural history of brainstem cavernomas – bothincidental and symptomatic; (ii) whether incidental lesions needto be excised; and (iii) whether there is enough evidence to provethat the outcome following surgery is better than the natural his-tory of these lesions, especially in symptomatic patients.

4.1. Natural history

The risk of hemorrhage in patients with brainstem cavernoma isapproximately 0.7% per patient year of life.2,4,6,11–13 Porter et al. re-ported that the annualized hemorrhage risk was 5% per person peryear and the rebleeding rate was 30% per person per year.5 Fritschiet al. also reported an average bleeding rate of 2.7% per year per le-sion and a rebleeding rate of 21% per year per lesion.6 In a prospec-tive report, the annual rate of repeated hemorrhage for brainstemlesions reported by Kondziolka et al. was 5% per lesion per yearcompared with 2.4% overall.14 In the current series, 69.2 % of ourpatients experienced rebleeding. However, the interval betweenhemorrhages was variable and unpredictable.

The risk of developing permanent deficits increases with eachsuccessive hemorrhage.15 In our series, patients with multiplehemorrhages had a greater number of cranial nerve deficits(81.2%) compared with patients who had experienced a singlehemorrhagic event (65%). Furthermore, chances of a complete pre-operative neurological recovery diminish after each successivehemorrhage. Only 6.25% of our patients with multiple preoperativehemorrhages recovered to their pre-hemorrhage state compared to20% of patients with a single episode of hemorrhage.

4.2. Presentation

Patients most commonly present with bleeding, combined withan acute onset of neurological deficits. Symptoms may manifest asa new deficit or as an exacerbation or recurrence of an existing orprevious neurological deficit. The onset of symptoms may occa-

sionally be gradual and may mimic demyelination, infarction, neo-plasm, or infection, in their clinical presentation.

Despite the risk of significant neurological impairment relatedto the location of lesion within the brainstem, bleeding is usuallylimited because of the low flow characteristics of cavernomas.16,17

Some authors have suggested that intralesional bleeding, due tothe rupture of caverns within the cavernoma, formation of newcysts, and possible reactive angiogenesis, may be responsible forthe dynamic nature and growth of some lesions. Conversely, signif-icant intracavernous hemorrhage may also destroy the lesion.

It is unclear whether pregnancy increases the risk of hemor-rhage in patients with cavernous malformations and some authorshave suggested that female hormonal factors may play a role.5

Estrogen receptors have been reported in a few cavernous malfor-mations from female patients by some authors.5,18,19

4.3. Associated venous anomalies

Previous studies have reported that venous malformations areassociated with cavernous malformations of the brainstem in 8–26% of patients.20,21 Fritschi et al., in an extensive review, reportedan incidence of approximately 8% of venous anomalies accompany-ing cavernomas.6 In our series, two patients (3.8%) with associatedvenous malformations were identified.

4.4. Surgical management

4.4.1. Decision for surgeryDefining criteria for selection of patients with brainstem caver-

nomas and surgery is challenging. The major considerations forsurgical selection are: (i) the location of the lesion (superficial ordeep-seated); and (ii) whether the lesion is incidental or symptom-atic. Most authors agree that incidental lesions should not be oper-ated, especially if deep-seated and small;7 others recommendsurgery for patients with progressive symptoms and with superfi-cially located cavernomas, where a surgical approach is possible.

Samii et al. recommended intervention for superficial caverno-mas if the patient is young, even for incidentally diagnosed lesionswithout hemorrhage.4 Additionally, they recommended surgery forpatients with progressive deterioration, with further hemorrhage,even though the cavernoma may not be superficial. Mathiesenet al. also advocated a similar philosophy and reported the possi-bility of reaching deeply located cavernomas and removing themwith a very low morbidity.12 Wang et al. included the followingas indications of surgery: (i) progressive neurological deficits; (ii)clinical presentations such as coma or cardiac or respiratory insta-bility; (iii) overt acute or subacute hemorrhage on MRI; or (iv)either cavernoma or hematoma reaching < 2 mm from the pial sur-face.11 Based on their observations, Hauck et al. emphasized thehigh risk of recurrences after a previous event and therefore, theneed for surgery after the first event.22 Our policy, for patientswho experience multiple hemorrhages and in whom the lesion islocated close to the wall of the fourth ventricle or lateral cistern,is to resect the lesion after the last hemorrhagic episode, as soonas neurological recovery or stabilization has been achieved. Sur-gery is ideally deferred in patients with intrinsic lesions withinthe paramedian floor of the fourth ventricle unless the patient israpidly deteriorating.

Indications for surgery for patients with clinically asymptom-atic brainstem cavernomas who have MRI-documented bleedingwill depend on the age of the patient and location of the lesion.Surgery is advised in young patients in whom there is radiologicaldocumentation of bleeding and the cavernoma is close to the floorof the fourth ventricle. However, if the lesion does not have pialcontact, surgery is not usually recommended and these patientsare managed conservatively. Patients over 65 years of age, who

G. Menon et al. / Journal of Clinical Neuroscience 18 (2011) 1210–1214 1213

have had brainstem cavernomas detected incidentally with orwithout associated comorbidities, are normally treated conserva-tively with regular reviews.

4.4.2. Timing of surgeryOptimal timing of surgery is less well defined. Some authors

perform surgery in the subacute stage, with a delay of several daysor weeks after the hemorrhage, when the patient is in a stable con-dition. Additionally, in the subacute stage MRI can better differen-tiate between the hematoma and the vascular malformation itself.However, some authors believe that surgery should be performedearlier, because post-bleed gliosis can make resection of the caver-noma, without damaging the surrounding tissue, difficult. Samiiet al. found no difference between operating in the subacute periodand operating after more than 3 months.4 Statistical comparisonshowed the presence of fewer motor deficits in the group of pa-tients who underwent resection within 3 months of the ictus. Inour series, of the six patients who had a poor outcome, four under-went surgery within the first 2 weeks. We found a poor plane ofcleavage in all six patients who underwent surgery in the first2 weeks after hemorrhage; hence, we prefer to defer surgery inthe acute phase and favour performing the intervention in the sub-acute phase once the patient has been stabilized.

4.4.3. Operative strategyThe main goals of surgery for brainstem cavernomas are to

achieve complete resection of the lesion and to avoid additionalneurological damage to the patient. Safe entry zones above and be-low the facial nucleus have been described and the importance ofan awareness of the anatomy of the floor of the fourth ventriclecannot be overemphasized.23 Intraoperative electrophysiologicalmonitoring has been used by various authors to determine safe en-try zones to approach brainstem lesions and thus avoid direct dam-age of cranial nerve nuclei.17,24 Unless the lesion is clearlyexophytic, alternative entry points such as the anterolateral ponsshould be considered as complications are less likely when enter-ing the brainstem via this zone. After the lesion is exposed, the sur-rounding hematoma is removed and the cavernous malformationexposed and dissected.

Table 4New postoperative deficits compared to those at presentation due to hemorrhagefrom brainstem cavernoma

Hauck et al. 200922 Current series

Motor deficitsPreoperative 57% 48.1%Postoperative 7% 26%

Cranial nerve deficitsPreoperative 86% 94.2%Postoperative 14% 21.7%

Table 5Reports in the literature of outcome following surgical management of brainstem caverno

Author Year No. patients Outcome i

Sindou et al.7 2000 12 83Steinberg et al.16 2000 42 95Samii et al.4 2001 36 61 > KPS =Kupersmith et al.31 2001 12 75Bertalanffy et al.17 2002 24 92Wang et al.11 2003 137 72Ferroli et al.8 2005 52 81Tarnaris et al.25 2007 6 33.33Hauck et al.22 2009 44 89Ohue et al.26 2010 36 92Current series 2010 23 71.4

� Numbers in parentheses indicate the number of patients. KPS = Karnofsky Performanc

Knowing the exact location of the cavernous malformationwithin the bleeding cavity is valuable for planning the surgical ap-proach. In deeply located cavernomas the use of neuronavigation ishighly recommended. It is important to use navigation in the earlystage of exposure to allay concerns regarding intraoperative brainshift. Neuronavigation, when applied with minimal brain retrac-tion and before large amounts of cerebrospinal fluid are drained,can precisely locate the cavernoma. Working around the bordersof the lesion ensures that bleeding is minimized and facilitates dis-section. After removal of the cavernous malformation meticuloushemostasis is essential. No effort is made to remove the hemosid-erin-stained gliotic tissue that surrounds the cavity of the hema-toma because it is unnecessary in the brainstem and may causeadditional neurological damage.

4.4.4. Surgical outcomesIn our series, the incidence of new postoperative neurological

deficits was clearly lower than preoperative deficits caused by sin-gle or multiple hemorrhages within the brainstem. For example,the rate of new cranial nerve deficits was only 21.7% and that ofmotor deficits was 26% compared with preoperative incidencesof 94% and 48%, respectively (Table 4).

In a series of 52 patients reported by Ferroli et al. in 2005, 42(80.8%) patients improved or remained stable.8 After an extensivereview of related literature over a 15-year period, Tarnaris et al.calculated that 87% of the patients who underwent surgery forbrainstem cavernomas showed good neurological status at thelong-term follow-up compared with 12.9% of patients whose neu-rological status had declined.25 In a recent article on surgical man-agement of brainstem cavernomas, Ohue et al. reported a majorityof patients (92%) who improved or were unchanged after surgery,with only three patients (8%) showing significant deterioration(Table 5).26

The figures listed above are comparable to those reported in ourseries, in which 71.4% of the patients after surgery were the sameor improved at the last follow-up review and six (28.6%) patientshad a poor outcome as measured by deterioration in mRS, primar-ily due to worsening limb power.

4.4.5. ComplicationsAlthough overall morbidity and mortality following surgery for

brainstem cavernomas is high, it should be noted that these pa-tients undergo extensive skull-base dissection and the postopera-tive complications are temporary and manageable. Earlytracheostomy and nasogastric tube feeding for indicated patientsminimizes the chances of postoperative pneumonia and poornutrition. In the series by Amin-Hanjan et al., a 14.2% permanentdisabling complication rate was observed.27 This figure is compara-ble to the complication rate of 9.5% in our series.

mas

mproved or same (%) Mortality (%) Follow-up (months)

0 (0/12)� 660 (0/42) 56.4

80 0 (0/34) 360 (0/12) 58.80 (0/24) 600 (0/137) 522 (1/52) 56.40 (0/6) 79.70 (0/44) 110 (0/36) 128.7 (2/23) 42

e Scale.

Table 6Outcome of conservatively managed patients with brainstem cavernomas

Author Year No. patients Outcome improved or same (%) Mortality (%) Follow-up (months)

Kupersmith et al.31 2001 25 96 0 (0/25)� 58.8Tarnaris et al.25 2007 15 46.7 0 (0/15) 79.7Current series 2010 29 51.8 3.7 (1/27) 48.0

� Numbers in parentheses indicate the number of patients/total.

1214 G. Menon et al. / Journal of Clinical Neuroscience 18 (2011) 1210–1214

4.4.6. Non-surgical managementOccasionally, non-surgical management of patients with brain-

stem cavernomas is recommended. In a study by Kupersmith et al.,conservatively managed patients with brainstem gliomas had abetter outcome in comparison to those who underwent surgery.28

Tarnaris et al. suggested that conservative management for brain-stem cavernomas may be more appropriate than surgery for indi-vidual patients and the results for both treatment options do notdiffer significantly in the long term.25 They reiterated the needfor evaluating the long-term follow-up of patients managed con-servatively (Table 6).

Conversely, worse outcomes for patients managed non-surgi-cally have also been reported in literature. In a meta-analysis byFritschi et al., at a mean follow-up period of 36 months, 34%(n = 30) of their patients managed conservatively were moder-ately-to-severely disabled or dead.6 Thirty patients (32.6%) wereworse on follow-up. In our series, 51.8% of patients had a good out-come and 44.4% had deterioration in their functional status.

4.4.7. Stereotactic radiosurgeryRadiosurgery has been recommended by some authors as a

treatment option. A reduction in the size of cavernomas after radi-osurgery has been reported and some authors believe that the an-nual risk of bleeding may be reduced with radiosurgery.29–31

5. Conclusion

The natural history of brainstem cavernomas differs from caver-nomas in other locations of the CNS. The annual rate of hemor-rhage and risk of rebleeding are much higher. Surgical resectioncan be achieved with acceptable risks and ideally should be per-formed in the subacute phase, 3–4 weeks after the last hemor-rhage. Surgery for brainstem cavernomas should be consideredprovided the lesion abuts the pial surface or is exophytic, and thereis history of either multiple hemorrhages or the patient has pro-gressive neurological deficits. Surgery attempted for lesions situ-ated at considerable depth carries risks of multiple deficits,especially cranial nerve palsies.

In our series, a better outcome was observed in the surgicallymanaged group compared to the conservative group; however, thisresult was not significant enough to refute the role of non-surgicalmanagement. Very few published series have critically comparedsurgery and conservative management for brainstem cavernomasand current management guidelines lack consensus. The naturalhistory of brainstem cavernomas appears more benign than waspreviously thought. The role of conservative management fordeep-seated lesions, incidentally diagnosed brainstem cavernomasin young patients, and neurologically intact patients who haverecovered following a single episode of hemorrhage should notbe discounted. Management of these lesions should be individuallytailored rather than adopting a generalized approach.

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