ORIGINAL PAPER

A randomized study of ventriculoperitoneal shuntversus endoscopic third ventriculostomy for the managementof tubercular meningitis with hydrocephalus

Pawan Goyal & Chhitij Srivastava & Bal Krishna Ojha &

Sunil K Singh & Anil Chandra & R. K. Garg &

Swati Srivastava

Received: 26 October 2013 /Accepted: 16 January 2014 /Published online: 4 February 2014# Springer-Verlag Berlin Heidelberg 2014

AbstractObjective This study aims at generating knowledge to under-stand the conditions in which either of the two procedures(endoscopic third ventriculostomy (ETV) and shunt) are betteroptions and to develop good practice guidelines for the treat-ment of tubercular meningitis (TBM) hydrocephalus.Methods This study was conducted on 48 patients in pediatricage group (less than or equal to 18 years) of TBM hydroceph-alus. The patients were randomized to one of the cerebrospinalfluid diversion procedures (ETV or shunt). The two proce-dures were compared for their outcome, both radiologicallyand clinically.Results Twenty-four cases underwent shunt, out of which 13(68%) cases were successful. Twelve (70.3%) cases belongedto grade 3, while one case was of grade 1. In ETV group, 10(42 %) cases had a successful outcome, out of which 7(38.8 %) cases were in grade 3, while 1 case each belongedto grades 1, 2, and 4. Incidence of ETV failure was more inyounger age group, i.e., <2 years (n=7), while no such corre-lation with age was found in shunt cases.Conclusion Though with the present study it looks like thatthe relative risk of ETV failure is higher than that for shunt,but the risk becomes progressively lower with time. There-fore, if patients survive the early high-risk period, they couldexperience a long-term survival advantage devoid of life-long

shunt-related complications. Though for definitive compari-son, a long-term study is needed

Keyword Tubercular meningitis hydrocephalus . VP shunt .

ETV . Outcome . Failure

Introduction

Tubercular meningitis (TBM) remains a problem in mostAsian countries and is now becoming an important illness inthe developed world due to migration. Hydrocephalus is oneof the commonest complications of TBM. It occurs in up to85 % of children with the disease and is more severe inchildren than in adults [15].

Ventriculoperitoneal (VP) shunt is the mainstay of treat-ment in patients of tubercular meningitis with hydrocephalus(TBMH). There have been several reports on the use of shuntin these patients, with varying degrees of success [9, 15].However, it is associated with lifelong complications [1, 3,14, 16]. Shunt blockage is very common in TBMH due tohigh cellularity and protein content of the patient’s cerebro-spinal fluid (CSF) [2, 15].

Recent work on CSF dynamics has shown possible expla-nations for the success of endoscopic third ventriculostomy(ETV) in TBMH. ETV enables CSF to permeate the previ-ously inaccessible areas and possibly normal CSF absorptionareas within the brain. It may allow the CSF to circulatethrough and clean the exudates from areas of the brain withpreviously impaired absorption [2]. The growing enthusiasmfor ETV is fueled largely by the assumption that ETV isinherently superior to shunt in the treatment of hydrocephalus.This assumption however has never been directly proven.Various authors have reported successful use of ETV in thesepatients [2, 4, 6, 7]. However, to the best of our knowledge, no

P. Goyal :C. Srivastava (*) : B. K. Ojha : S. K. Singh :A. ChandraDepartment of Neurosurgery, King George’s Medical University,Lucknow, Indiae-mail: drchhitij@yahoo.co.in

R. K. GargDepartment of Neurology, King George’s Medical University,Lucknow, India

S. SrivastavaDeparment of Pathology Vivekanand Polyclinic and Instituteof Medical Sciences, Lucknow, India

Childs Nerv Syst (2014) 30:851–857DOI 10.1007/s00381-014-2371-1

randomized studies comparing ETV with shunt in TBMHexist.

We therefore have done a randomized controlled trial todirectly compare the outcome of the two treatment modalities,thus excluding the selection bias. In the course of the study, wehave also tried to find a correlation between duration ofillness, duration of antitubercular treatment (ATT), age, pre-operative clinical status of the patient, and the outcome of thetwo modalities.

Materials and methods

This study was conducted on 48 patients in pediatric age group(less than or equal to 18 years). The diagnosis of TBM wasestablished using standardized clinical case definition [11]. Asper the study of Palur et al., [14], patients were grouped into 4grades of TBMH (modified Vellore grade). For younger chil-dren, especially those too young to have reliable languageskills, the Pediatric Glasgow Coma Scale was used [20].

Inclusion criteria

Patients diagnosed as definite, probable, or possible cases ofTBM according to consensus case definition [11] along withclinical presentation of raised intracranial pressure and radio-logical evidence of hydrocephalus were included in the study.Any patient who has already undergone CSF diversion pro-cedure (shunt or ETV) earlier was excluded from the study.

Study design

After the patients had been included in the study, they wererandomized to one of the CSF diversion procedures (VP shuntor ETV). A randomized dichotomous scheme for procedureallocation was developed before the start of the study for allthe expected 48 TBM hydrocephalus patients. The randomnumbers for this purpose were generated. Patient’s preopera-tive clinical and radiological profile was collected. All essen-tial per-operative (Fig. 1) findings were recorded.

CSF sample collected during the CSF diversion procedure(either shunt or ETV) was subjected to detailed analysis. Thisincluded total cell counts, differential cell count, and sugar,protein, staining for AFB, culture, and polymerase chainreaction (PCR) for tuberculosis.

Twenty-four patients underwent standard VP shunt proce-dure through parietal burr hole. Type of shunt (either lowpressure or medium pressure) used was based on openingflow of CSF on ventricular catheterization.

In 24 patients who underwent ETV, Lotta Hopkins endo-scope of 6° with 6.1 mm outer diameter was used (Fig. 2). All

patients received standard antitubercular therapy (irrespectiveof type of CSF diversion) based on WHO guidelines.

Anticonvulsants were given in all cases until 6 months offollow up. All the patients were evaluated at 1, 3, and 6monthsin follow up by thorough clinical and radiological assessment.

They were assessed for the following:

1. Clinical outcome—recorded as success or failure on the basisof clinical and radiological assessment at admission, dis-charge, and at follow up. Outcome was labeled as follows:

Successful—a patient showing improvement in his/her clinical and radiological profile (head CT scan)Failure—a patient not improving or deteriorating andrequiring another surgical intervention (shunt in caseof ETV group or shunt revision/removal in case ofshunt group)

2. Radiological assessment: to assess the radiologicalimprovement/deterioration on each follow up.

3. Analysis of complications are the following:

For VP shunt: shunt infection, shunt extrusion, shuntmalfunction, shunt ascites, etc.For ETV: preoperative complications, CSF leak,meningitis, cranial nerve injuries, hypothalamic dys-function, etc.

At the end of study, appropriate statistical tests were usedso to analyze the data collected.

Results

Demographic patterns

The age of ETVand shunt groups ranged from 0.5–16 and 0.5–12.0 years, respectively, with mean (±SD) 4.21±4.60 and 4.31±3.72 years.Maximumpatients in both groupswere between 0 and

Fig. 1 Multiple tuberculoma on ventricular ependymal wall

852 Childs Nerv Syst (2014) 30:851–857

3 years. In both groups, there were 7 females and 17 males, withpercentage being higher onmales (70.8%) than females (29.2%).

Classification of cases

On the basis of the standardized case definition, patients weregrouped into definitive, 17 (35 %); probable, 30 (63 %); andpossible, 1 (2 %) cases of tuberculosis.

Clinical outcome

Twenty-four cases underwent shunt, out of which 13(54.2 %) cases were successful (Table 1). Four patients(16.7 %) require repositioning of shunt. There were twodeaths in this group. First patient was in poor grade(Vellore grade 4, GCS—6). Another patient was admit-ted in Vellore grade 3, who died in postoperative perioddue to associated military tuberculosis.

In ETV group, 10 (41.7%) cases had a successful outcome,while in another 10 cases (41.7 %), VP shunt was done inpostoperative period for ETV failure. Two patients lost in thefollow up period. There were two deaths in this group. Firstpatient (Vellore grade 3) expire due to associated poor chestcondition, while another patient was discharged in satisfactorycondition, which later reported to us for CSF leak and died dueto fulminant meningitis.

Modified Vellore grading

Modified Vellore grading (MVG) scores in both groups werecomparable at the start of the study (Fig. 3). It decreased(improved) after the treatment in both groups, and the im-provement was higher in shunt group (63.6 %) as compared toETV group (56.1 %). The difference in improvement in theshunt group as compared to ETV was 7.5 %, which is of nostatistical significance.

Figure 3 is the graphical representation of comparativeimprovement in the MVG score of both groups over aperiod of 6 months. It is evident that the improvement inshunt group occurred at a brisk pace and was better ascompared to ETV.

Predictors of clinical outcome

Among the various predictors of outcome studied by binarylogistic regression analysis, modified Vellore grading wasfound to have some impact on outcome (high odds ratio,6.41) (Table 2). No other variable had any effect on theoutcome.

Complications

In ETV group, CSF leak was noted in seven cases; twopatients developed meningitis, out of which one patient

Table 1 Distribution of the clinical outcome of two groups

Outcome ETV(n=24)

Shunt(n=240

Χ2 value(DF=3)

P value

Successful 10 (41.7 %) 13 (54.2 %) 4.25 0.236Failure 10 (41.7 %) 4(16.7 %)

Death 2 (8.3 %) 2 (8.3 %)

Lost to follow up 2 (8.3 %) 5 (20.8 %)

Fig. 2 a Thick third ventriclefloor before thirdventriculostomy. b Floor of thethird ventricle afterventriculostomy

Fig. 3 Mean modified Vellore grading scores of two groups over theperiods

Childs Nerv Syst (2014) 30:851–857 853

eventually died. Three patients had bulge at the ETVsite. Shunt-related complications occurred in four(17 %) patients and consisted of an obstruction at thelower end of the shunt in three (13 %) cases, leading torevision, and one (4 %) patient had an infection at theshunt chamber site, leading to skin excoriation andmeningitis.

Discussion

To the best of our knowledge, there have been no randomizedtrial done previously to compare the outcome of ETV andshunt in TBMH.

Radiological analysis

Based on reduction of periventricular lucency, decreasein the size of ventricles, and reappearance of CSF in

subarachnoid space (Fig. 4), it was observed that pa-tients in the shunt group showed 89 % recovery in thefeatures of TBMH over a period of 6 months, while inETV group, the recovery was 74.8 %. In the study doneby Yadav et al., in patients operated for ETV, radiolog-ical recovery was only 52 % within 3 weeks [21].Singh et al. had seen radiological recovery in 55.6 %of his patients over a period of 12 weeks [18]. Thissuggests that decrease in the size of ventricle occursslowly after ETV and may not correlate well with theclinical outcome.

Failure to improve after ETV does not always mean thatETV is malfunctioning. It could be related to the associatedfeatures of TBM such as infarcts as seen in this study (sixcases had infarcts on CT, out of which four failed to recoverafter ETV). Yadav et al. also had similar opinion [21]. Amultiple regression analysis done by Kalita et al. suggestedinfarction on CT scan to be one of the most important predic-tor of the outcome of TBM at 6-month follow up [8].

Table 2 Predictors of the clinicaloutcome in ETV, shunt, and total(ETV + shunt) by binary logisticregression analysis

Predictors ETV (n=24) Shunt (n=24) Total (n=48)OR (95 % CI) OR (95 % CI) OR (95 % CI)

Age: ≤2 years

>2 years 0.50 (0.10–2.60) 1.09 (0.21–5.76) 0.70 (0.22–2.19)

Duration of illness

≤2 months

>2 months 0.56 (0.11–2.90) 1.29 (0.23–7.05) 0.88 (0.27–2.82)

CSF proteins

≤1 g/dl

>1 g/dl 0.93 (0.16–5.54) 1.40 (0.28–7.02) 1.04 (0.33–3.30)

CSF cell count

≤50 cells/mm3

>50 cells/mm3 0.56 (0.11–2.90) 1.03 (0.21–5.15) 0.72 (0.23–2.25)

History of ATT

No

Yes 0.60 (0.11–3.34) 0.60 (0.11–3.40) 0.60 (0.18–2.03)

Modified Vellore grade

1

2 1.70 (0.97–2.51) 1.60 (0.45–2.14) 2.15 (1.13–3.24)

3 2.67 (1.10–4.27) 2.24 (0.97–3.85) 3.68 (2.21–5.33)

4 3.40 (2.32–7.69) 2.76 (2.04–5.72) 6.41 (2.79–9.57)

Focal deficit

No

Yes 1.75 (0.31–9.75) 0.67 (0.13–3.45) 1.04 (0.33–3.30)

Cranial nerve deficit

No

Yes 2.22 (0.33–14.80) 0.67 (0.13–3.45) 1.05 (0.32–3.45)

Duration of altered sensorium

8–14 days 3.57 (0.41–5.14) 0.60 (0.09–2.99) 1.26 (0.33–4.84)

>14 days 4.43 (1.59–7.95) 1.00 (0.13–4.57) 1.62 (0.37–7.20)

854 Childs Nerv Syst (2014) 30:851–857

Outcome

Prediction of outcome of TBM is difficult because of itsprotracted course, diversity of underlying pathological mech-anisms, variation of host immunity, and virulence of myco-bacterium tuberculosis [13]. Modified Vellore grading is thebest and most consistent predictor of outcome following sur-gery in patients with TBM hydrocephalus. Table 3 shows thatthe clinical outcome is consistently poor in grade IV in allstudies.

Overall success rate in ETV group in our study was 41.7%,which is less compared to some of the previous studies(Table 4). This may be due to the fact that 88 % of patients inour study belonged to grades 3 and 4 as compared to 54% in thestudy done by Husain et al. [5] and only 19 % in the studydone by Yadav et al. [21]. We had a 100 % success rate ingrade 1 similar to Yadav et al., while in grade 4, it was 33.3 %in our study and 50 % in the study done by Yadav et al.

Singh et al. [18] and Chugh et al. [2] graded their patientson the basis of MRC grade. They too found that the resultswere poorer in poor grades as compared to better grades.

Age, CSF cells, and proteins did not have any impact onthe outcome of CSF diversion procedures. Other studies .[12,14]. related to shunt have not seen any correlation of the abovevariables with the outcome. We did not find any correlation ofthe outcome with the duration of illness in the shunt group.

Also, earlier studies in the shunt group .[12, 19] .did not findany correlation of the outcome with the duration of illness.

In ETV group, we had better results in patients with longerduration of illness (>2 months). There was 50 % success ratein patients with the longer duration of illness as compared to35.7 % in patients with the shorter duration (<2 months).Yadav et al. [21] and Chugh et al. [2] also found that patientswith chronic disease had better outcome as compared to

Fig. 4 a Case of TBM hydrocephalus showing dilated ventricles, periventricular lucencies, and effaced sulci. b CT scan of the same patient 1 monthafter ETV. Periventricular lucencies have disappeared and sulci are well visualized. Note that ventriculomegaly is still persisting

Table 3 Shunt group: preoperative Vellore grade versus poor outcomefollowing shunt surgery

Author No. ofpatients

III(percentage ofpoor outcome)

IV(percentage ofpoor outcome)

Follow up(months)

Palur et al.[14]

114 51.9 100 45.6

Mathew et al.[12]

32 21.8 91.7 23.1

Agarwal et al.[1]

37 60 100 9

Singh et al.[17]

140 39.7 65.5 NA

Present studya 24 29.4 100 6

Poor outcomemeans percentage of patients with death or severe disabilitya Poor outcomemeans patients with death, failure, and lost to follow up inour study

Childs Nerv Syst (2014) 30:851–857 855

patients with acute illness. This could be due to high incidenceof complex hydrocephalus in acute phase of illness.Moreover,in acute stage of illness, signs of meningitis predominate,leading tomore chance of failure. Relationship of preoperativeATT with successful endoscopic outcome was found but wasstatistically insignificant. Chugh et al. [2] also found similarobservations, i.e., statistically insignificant positive correla-tion (Mann-Whitney U test=40.50, P=0.13). Probably, theresolution of the basal exudates following the commencementof ATT could be a reason that the endoscopic outcome wasbetter in patients who were treated with ATT for a longerperiod preoperatively. No such correlation was found in theshunt group in our study. Patients with altered sensorium for alonger period (>7 days) were found to have lower success ratein the ETV group, but not in shunt group. But statisticalsignificance of such correlation could not be established onbinary logistic regression analysis. Mathew et al. [12] andPalur et al. [14] did not also find any correlation of successwith the duration of altered sensorium.

Complications

In ETV group, CSF leak was noted in seven cases, while twopatients developed meningitis, out of which one patient even-tually died. Husain et al. [5] had complications in 3 of 28patients undergoing ETV, while Yadav et al. [21] reported leakin 6 out of 50 patients.

The shunt infection rate in our study (4 %) was much lesscompared to the other recent studies (e.g., Lamprecht et al.,13.8 % [10]; Agarwal et al., 14 % [1]).

Shunt malfunction rate in our study (13 %) leading torevision is similar to other studies like Lamprecht et al.,14 % [10] and Agarwal et al., 16 % [1]).

Shunt versus ETV in TBMH

It was found that patients in the shunt group showimprovement in the modified Vellore grading at a fasterrate as compared to ETV group. At 6 months, thedifference in improvement in the shunt group (63.6 %)as compared to ETV (56.1 %) was 7.5 %, which is ofno statistical significance. Patients undergoing shuntshow more radiological recovery and that too at a faster

rate as compared to ETV group. Patients undergoingETV have an arrested hydrocephalus type of picture.This may be due to the fact that after ETV, patientsCSF dynamics get into an equilibrium in which en-larged ventricles are not due to raised intracranial pres-sure. Most of the ETV failures occurred in less than3 months of surgery (8 out of 10). This suggests thatthe risk of ETV failure is higher in the early phase oftreatment. Therefore, if the patient survives the earlyhigh-risk period, they could experience long-term treat-ment survival advantage.

Conclusion

VP shunting has better immediate outcome in hydro-cephalus as compared to ETV. In the initial period,patients undergoing ETV should be watched closelyfor ETV failure, as in early phase, ETV failure andcomplications are more common in this group as com-pared to patients undergoing VP shunt. Over a period of6 months, clinical as well as radiological recovery inETV catches up with that of shunt. As most of the ETVfailure occurs in the initial 3 months of surgery and it isa proven fact that shunt has life-long risk of malfunc-tion and infection, so there could be some rationale ofattempting ETV in TBM hydrocephalus because a suc-cessful ETV might confer long-term benefits over shunt.As the chances of ETV failure increases in active tu-berculosis, so it is better to attempt ETV in the laterphase after starting antitubercular treatment. ETV ismore physiological than shunt surgery; hence, long-term outcome of hydrocephalus may tilt in favor ofETV, performed after adequate chemotherapy with anti-tubercular drugs and steroids.

Although the number of cases in the present study islimited, it certainly offers a comparison of two alter-nating ways of treating hydrocephalus in TBM. It iscertainly worth trying ETV before subjecting the pa-tient to shunt. More randomized studies and longerfollow up monitoring are required to critically evaluatethe efficacy of ETV in comparison to shunt, its predic-tive factors in outcome, and timing of surgery inTBMH.

Limitations of study

Forty-eight cases taken in this study are very limited. Morenumber of cases are required for a good comparative study.Six-month follow up is another limiting factor. Follow up oflonger duration may tilt the result in favor of endoscopic thirdventriculostomy.

Table 4 ETV group:outcome following ETV Author Success rate (%)

Singh et al. [18] 77

Hussain et al. [5] 68

Chugh et al. [2] 73

Yadav et al. [21] 58

Figagi et al. [4] 41

Present study 41.7

856 Childs Nerv Syst (2014) 30:851–857

Acknowledgement This study was funded by intramural research cellgrant, King George’s Medical University, Lucknow, India.

References

1. Agrawal D, Gupta A, Mehta VS (2005) Role of shunt surgery inpediatric tubercular meningitis with hydrocephalus. Indian Pediatr42:245–50

2. Chugh A, Husain M, Gupta RK, Ojha BK, Chandra A, Rastogi M(2009) Surgical outcome of tuberculous meningitis hydrocephalustreated by endoscopic third ventriculostomy: prognostic factors andpostoperative neuroimaging for functional assessment ofventriculostomy. J Neurosurg Pediatr 3:371–7

3. Eghwrudjakpor PO, Allison AB (2010) Evolution of surgical inter-ventions for hydrocephalus: patient preferences and the need forproper information. Internet J Med Update 5:55–62

4. Figaji AA, Fieggen AG, Peter JC (2007) Endoscopy for tuberculoushydrocephalus. Childs Nerv Syst 23:79–84

5. Husain M, Jha DK, Rastogi M, Husain N, Gupta RK (2005) Role ofneuroendoscopy in the management of patients with tuberculousmeningitis hydrocephalus. Neurosurg Rev 28:278–83

6. Husain M, Jha D, Vatsal DK, Thaman D, Gupta A, Husain N et al(2003) Neuro-endoscopic surgery—experience and outcome analysisof 102 consecutive procedures in a busy neurosurgical centre ofIndia. Acta Neurochir 145:369–76

7. Jonathan A, Rajshekhar V (2005) Endoscopic third ventriculostomyfor chronic hydrocephalus after tuberculous meningitis. Surg Neurol63:32–5

8. Kalita J, Misra UK (1999) Outcome of tuberculous meningitis at 6 and12months: amultiple regression analysis. Int J Tuberc LungDis 3:261–5

9. Kemaloglu S, Ozkan U, Bukte Y, Ceviz A, Ozates M (2002) Timingof shunt surgery in childhood tuberculous meningitis with hydro-cephalus. Pediatr Neurosurg 37:194–8

10. Lamprecht D, Schoeman J, Donald P, Hartzenberg H (2001)Ventriculoperitoneal shunting in childhood tuberculous meningitis.Br J Neurosurg 15:119–25

11. Marais S, Thwaites G, Schoeman JF, TorokME,Misra UK, Prasad Ket al (2010) Tuberculous meningitis: a uniform case definition for usein clinical research. Lancet Infect Dis 10:803–12

12. Mathew JM, Rajshekhar V, Chandy MJ (1998) Shunt surgery forpoor grade patients with tuberculous meningitis and hydrocephalus:effect of response to external ventricular drainage and other factors onlong-term outcome. J Neurol Neurosurg Psychiatry 65:115–8

13. Misra UK, Kalita J, Roy AK, Mandal SK, Srivastava M (2000) Roleof clinical, radiological and neurophysiological changes in predictingthe outcome of tuberculous meningitis: a multivariable analysis. JNeurol Neurosurg Psychiatry 68:300–3

14. Palur R, Rajshekhar V, Chandy MJ, Joseph T, Abraham J (1991)Shunt surgery for hydrocephalous in tubercular meningitis: a long-term follow-up study. J Neurosurg 74:64–9

15. Rajshekhar V (2009) Management of hydrocephalus in patients withtuberculous meningitis. Neurol India 57:368–74

16. Sil K, Chatterjee S (2008) Shunting in tuberculous meningitis: aneurosurgeon’s nightmare. Childs Nerv Syst 24:1029–32

17. Singh D, Kumar S (1996) Ventriculoperitoneal shunt in post tuber-cular hydrocephalus. Ind Pediatr 33:854–5

18. Singh D, Sachdev V, Singh AK, Sinha S (2005) Endoscopicthird ventriculostomy in post-tuberculous meningitic hydro-cephalus: a preliminary report. Minim Invasive Neurosurg48:47–52

19. S r i k an t h a U , Morab JV, Sa s t r y S , Ab r aham R ,Balasubramaniam A, Somanna S et al (2009) Outcome ofventriculoperitoneal shunt placement in grade IV tubercularmeningitis with hydrocephalus: a retrospective analysis in 95patients. J Neurosurg Pediatr 4:176–83

20. Teasdale G, Jennett B (1974) Assessment of coma and impairedconsciousness. A practical scale. Lancet 2:81–4

21. Yadav YR, Parihar V, Agrawal M, Bhatele PR (2011) Endoscopicthird ventriculostomy in tubercular meningitis with hydrocephalus.Neurol India 59:855–60

Childs Nerv Syst (2014) 30:851–857 857