Shunt surgery in patients with hydrocephalus and white matter changes

Clinical article

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Object

Patients with idiopathic normal pressure hydrocephalus (iNPH) often present with impaired gait and cognition together with ventricular enlargement and normal intracranial pressure. Many have vascular risk factors as well as periventricular and deep white matter changes on MR imaging. Abnormal CSF dynamics, that is, high resistance to outflow or improvement after CSF drainage, indicate good effects of shunt surgery.

The authors examined whether the worst-case iNPH patients with extensive vascular white matter disease and normal CSF dynamics would benefit from shunt surgery. These patients also fulfilled the criteria for Binswanger disease. Therefore, a randomized controlled double-blind study was performed.

Methods

Fourteen consecutive patients fulfilling the above criteria were randomized to receive either open or closed shunts. At 3 months after surgery, the patients with initially ligated shunts had their shunts opened. Clinical evaluation consisting of 7 quantitative psychometric and 6 continuous gait tests was performed preoperatively and 3 and 6 months after surgery.

Results

Patients randomized to receive open shunts had improved motor (30% increase) and psychometric (23% increase) scores 3 months after shunt placement. There were no significant changes between the 3- and 6-month follow-up in these same patients. Conversely, those with initially ligated shunts were unchanged during the first 3-month period, although they improved in both motor (28%) and cognitive (18%) functions following removal of the ligature.

Conclusions

Patients with enlarged ventricles, hydrocephalic symptoms, and extensive vascular white matter changes benefit from shunt surgery.

Abbreviations used in this paper: BD = Binswanger disease; FOV = field of view; iNPH = idiopathic normal pressure hydrocephalus; Rout = resistance outflow.

Abstract

Object

Patients with idiopathic normal pressure hydrocephalus (iNPH) often present with impaired gait and cognition together with ventricular enlargement and normal intracranial pressure. Many have vascular risk factors as well as periventricular and deep white matter changes on MR imaging. Abnormal CSF dynamics, that is, high resistance to outflow or improvement after CSF drainage, indicate good effects of shunt surgery.

The authors examined whether the worst-case iNPH patients with extensive vascular white matter disease and normal CSF dynamics would benefit from shunt surgery. These patients also fulfilled the criteria for Binswanger disease. Therefore, a randomized controlled double-blind study was performed.

Methods

Fourteen consecutive patients fulfilling the above criteria were randomized to receive either open or closed shunts. At 3 months after surgery, the patients with initially ligated shunts had their shunts opened. Clinical evaluation consisting of 7 quantitative psychometric and 6 continuous gait tests was performed preoperatively and 3 and 6 months after surgery.

Results

Patients randomized to receive open shunts had improved motor (30% increase) and psychometric (23% increase) scores 3 months after shunt placement. There were no significant changes between the 3- and 6-month follow-up in these same patients. Conversely, those with initially ligated shunts were unchanged during the first 3-month period, although they improved in both motor (28%) and cognitive (18%) functions following removal of the ligature.

Conclusions

Patients with enlarged ventricles, hydrocephalic symptoms, and extensive vascular white matter changes benefit from shunt surgery.

Idiopathic normal pressure hydrocephalus is characterized by the deterioration of gait and balance often in conjunction with cognitive and bladder dysfunction. Enlargement of the ventricular system and normal intracranial pressure are constant features. The disorder is caused by disturbed CSF dynamics13 and is treated by shunt surgery. Currently, patients and CSF dynamics are best evaluated using CSF drainage, an infusion test, or intracranial pressure wave analyses,11,23,30 all methods of limited predictive value.23 Vascular risk factors are often seen in patients with iNPH. White matter changes in the periventricular and deep white matter are also frequently reported. However, some studies have indicated no negative impact of white matter changes on the effects of shunt surgery.16,19,27

Periventricular white matter changes were initially described in patients with small vessel disease in the brain, and the cause was believed to be microangiopathy, small multiple infarcts in the periventricular and deep white matter, and ongoing white matter degeneration.2 Patients with vascular risk factors and extensive white matter changes frequently present with symptoms and signs similar to those occurring in patients with iNPH. They are often classified as having BD (Table 1)4 or subcortical arteriosclerotic encephalopathy. Ventricular enlargement is not a criterion of BD but is frequently reported in the later stages of the disorder.3 No effective cure is currently available for patients with BD.

TABLE 1:

Criteria for BD according to Bennett et al.*

  1. dementia confirmed by neuropsychological tests

  2. 1 finding from 2 of the following 3 groups:

    • a vascular risk factor or systemic vascular disease

    • focal cerebrovascular disease (for example, a history of stroke or demonstration of a focal pyramidal or sensory sign)

    • “subcortical” cerebral dysfunction (for example, a parkinsonian magnetic or “senile” gait, parkinsonian or gegenhalten rigidity, or a history of incontinence secondary to spastic bladder)

  3. radiology: bilat leukoaraiosis on CT or bilat & multiple or diffuse high-signal T2-weighted lesions > 2 x 2 mm on MRI

proposed criteria lose their validity in the presence of
  1. multiple or bilat cortical lesions on CT or MRI; or

  2. severe dementia (for example, MMSE score <10)

* From Bennett et al: J Neurol Neurosurg Psychiatry 53:961–965, 1990. Abbreviation: MMSE = Mini-Mental State Examination.

We have observed that patients with hydrocephalic symptoms and ventricular enlargement improve after shunt surgery despite having negative CSF dynamics tests and extensive white matter lesions. Nonetheless, without guidelines or appropriate therapeutic studies in a patient population with severe vascular comorbidity and a high risk of complications, it is difficult to advocate shunt surgery. Therefore, we decided to perform a double-blind study, randomizing a group of patients to surgical treatment with either open or closed shunts.

Methods

Patient Population

Fourteen consecutive patients presenting with symptoms and signs of iNPH, ventricular enlargement (Evans Index > 0.30), and extensive white matter changes (rating of 2 [2 patients] or 3 [12 patients] on the white matter lesion score of the Wahlund Scale; Fig. 1)29 between October 2004 and October 2008 at Sahlgrenska University Hospital were included in this study. All patients were nonresponders on the CSF tap test30 and had an Rout < 12 mm Hg/ml/min.8

Fig. 1.
Fig. 1.

Two FLAIR MR images showing white matter disease (Wahlund Score 3) and ventriculomegaly.

There were 5 women and 9 men with a mean age of 75 years (range 60–82 years). Ten patients had hypertension, 1 had diabetes, and 2 had other cardiovascular disorders. Eleven patients were on antiplatelet therapy with acetylsalicylic acid, 75 mg daily (10 patients) or 160 mg daily (1 patient). The mean duration of symptoms was 36 months (range 10–120 months). The mean Mini-Mental State Examination score was 22.5 (range 16–28).

Clinical Assessment

The clinical examination was performed using 7 quantitative psychometric and 6 continuous gait tests in accordance with a previously described protocol.5,16

The psychometric tests included the Bingley Visual Memory Test (learning and memory), Identical Forms (perceptual speed and accuracy), Reaction Time Test, Grooved Pegboard (manual dexterity), Rey Auditory Verbal Learning Test (verbal learning and memory), Tracks Task (motor speed), and Stroop Test (speed, response selection, and inhibition). All these tests have been used in patients with iNPH and have been shown to be valid and sensitive to postoperative improvement.16

The gait analysis included the time in seconds needed to sit up from the supine position to the edge of the bed; the time in seconds needed to walk 10 m; the time in seconds needed to climb up and down 6 flights of stairs; the number of steps needed to turn 180°; the time in seconds needed to rise from a chair, walk 3 m and back, and sit down again; and, finally, the number of steps needed to walk 3 m backward (Table 2).6

TABLE 2:

Changes in psychometric and motor performance in 14 patients randomized to open or ligated shunts*

ParameterMean (range)
Open ShuntLigated Shunt
from baseline to 3 mos after op
 psychometric tasks
  Bingley Test23 (−18 to 100)−6 (−29 to 13)
  Identical Forms57 (−40 to 100)35 (−17 to 100)
  Reaction Time Test19 (3–28)3 (−24 to 31)
  Grooved Pegboard14 (−14 to 49)−2 (−13 to 9)
  RAVLT38 (−18 to 100)−18 (−59 to 6)
  Tracks Test9 (−32 to 27)−2 (−26 to 29)
  Stroop Color Naming0 (−52 to 27)−4 (−24 to 23)
 motor tasks
  time to sit upright from lying down in secs38 (−50 to 100)24 (−40 to 100)
  time to walk 10 m in secs33 (0–64)−21 (−100 to 10)
  time to climb up & down 6 flight of stairs in secs36 (0–90)0 (−13 to 13)
  time to rise from chair, walk 3 m & back, & sit down in secs18 (−14 to 88)−1 (−87 to 39)
  no. of steps to turn 180°10 (−50 to 42)−8 (−33 to 0)
  no. of steps to walk 3 m backwards45 (9–84.6)9 (−44 to 38)
from baseline to 6 mos after opopen shuntopened after 3 mos
 psychometric tasks
  Bingley Test20 (−38 to 100)37 (−20 to 67)
  Identical Forms39 (−47 to 100)23 (−13 to 100)
  Reaction Time Test9 (−21 to 48)10 (−31 to 49)
  Grooved Pegboard12 (−9 to 62)20 (9–49)
  RAVLT23 (−44 to 100)16 (−23 to 56)
  Tracks Test2 (−43 to 27)9 (−28 to 55)
  Stroop Color Naming−18 (−66 to 24)12 (−19 to 34)
 motor tasks
  time to sit upright from lying down in secs22 (−50 to 100)34 (−100 to 100)
  time to walk 10 m in secs34 (−5 to 70)27 (0–83)
  time to climb up & down 6 flight of stairs in secs21 (−100 to 90)22 (−5 to 57)
  time to rise from chair, walk 3 m & back, & sit down in secs22 (−27 to 86)18 (−23 to 39)
  no. of steps to turn 180°21 (−50 to 100)44 (0–75)
  no. of steps to walk 3 m backwards51 (9–100)23 (−13 to 57)

* Changes expressed in percentages maximized to 100%. Abbreviation: RAVLT = Rey Auditory Verbal Learning Test.

Magnetic Resonance Imaging Protocol

The entire brain was visualized with a 1.5-T Gyroscan Intera 9.1 system (Philips Medical Systems) using an 8-channel head coil and parallel imaging with sensitivity encoding. The brain imaging protocol involved 1) axial sequences yielding proton density (TR 2100 msec, TE 44 msec, FOV 230, and sense factor 2) and T2-weighted turbo spin echo axial images (TR 3000 msec, TE 100 msec, FOV 230, sense factor 2, with 3-mm-thick slices and 0.3-mm gap); 2) an axial FLAIR sequence (TR 11,000 msec, TE 140 msec, FOV 230, inversion recovery time 2800 msec, sense factor 2, with 5-mm-thick slices and 1-mm gap); and 3) a sequence yielding axial T1-weighted inversion recovery images (TR 4730 msec, TE 10 msec, FOV 200, inversion recovery time 400 msec, sense factor 2, with 2-mm thick slices).

Resistance to Outflow and CSF Tap Test

A CSF dynamic examination was performed using a computerized lumbar infusion test with the constant infusion of 1.5 ml/minute of saline.9 Resistance to outflow was calculated and expressed in mm Hg/ml/min. The mean Rout in the group was 10.2 mm Hg/ml/min, with a range between 8.2 and 11.8 mm Hg/ml/min.

The CSF tap test was performed by withdrawing 50 ml of CSF. Patients were examined the day before the test and 3 hours after the tap by using the following tests: Identical Forms, Bingley Visual Memory Test, Reaction Time Test, and the time in seconds needed to walk 10 m. Improvement on the walking test and 2 of the 3 psychometric tests was considered a positive tap test. Significant improvement for the different tests was defined as follows: Identical Forms, 25%; Bingley Visual Memory Test, 25%; Reaction Time Test, 5%; and walking test, 5%.30

Randomization Procedure and Surgery

After their inclusion into the study, patients were randomized to shunt surgery with either an open or a ligated ventriculoperitoneal shunt. The randomization procedure in blocks of 4 was done in the operating theater directly prior to surgery, and the result was disclosed to neither the patients nor the clinical examiners during the study.

All shunts had ventricular catheters inserted through a right-sided frontal bur hole and into the right lateral ventricle as well as a Strata Valve (Medtronic PS Medical) with a pressure setting of 1.0, corresponding to an opening pressure of 5.1 mm Hg.20 Ligation of the shunt was performed by constricting the distal tube of the shunt with a dural clip behind the right ear distal to the valve. Medication with acetylsalicylic acid was temporarily withdrawn for 1 week before and 1 week after surgery.

At baseline, the patients with initially ligated shunts did not differ from those with initially open shunts in regard to sex, age, Mini-Mental State Examination score, resistance outflow, or duration of symptoms. The groups performed similarly on all psychometric and motor tasks except for 2 tasks (both in favor of the group with ligated shunts; Table 3).

TABLE 3:

Baseline psychometric and motor performances in 14 patients randomized to open or ligated shunts*

ParameterMean (range)p Value
Open ShuntsLigated Shunts
psychometry
 Bingley Test3.4 (1.5–5.5)3.9 (1.5–6)NS
 Identical Forms6.1 (0.5–11.75)13.0 (5–19)<0.01
 Reaction Time Test419.0 (219–576)373.0 (276–600)NS
 Grooved Pegboard668.0 (221–1230)284.0 (149–605)<0.05
 RAVLT19.3 (10–32)27.0 (18–40)NS
 Tracks Test38.3 (24–53)42.9 (22–60)NS
 Stroop Color Naming160.0 (112–207)138.7 (67–187)NS
motor tasks
 time to sit upright from lying down in secs13.4 (2–46)23.5 (4–110)NS
 time to walk 10 m in secs25.3 (9–50)25.9 (11.5–94)NS
 time to climb up & down 6 flights of stairs in secs42.9 (10–100)37.4 (8–145)NS
 time to rise from chair, walk 3 m & back, & sit down in secs33.6 (10–92)20.8 (14–40)NS
 no. of steps to turn 180°4.3 (3–6)7.3 (3–20)NS
 no. of steps to walk 3 m backwards39.4 (11–65)32.2 (10–56)NS

* NS = not significant.

† Mann-Whitney U-test.

Three-Month Follow-Up

Patients were reexamined 3 months after surgery by using the same MR imaging protocol and same gait and psychometric tests as those applied preoperatively. A new infusion test was performed in the operating theater, validating the function of the shunt system.12 The result of the test was disclosed to neither the patients nor the clinical examiners.

Following the infusion test, the patients with closed shunts had their retroauricular wounds opened and the clip removed, whereas the patients with an open shunt underwent a sham opening with a superficial incision in the retroauricular scar and resuturing.

Six-Month Follow-Up

Six months after surgery, patients were reexamined using MR imaging and the same clinical tests and underwent an infusion test to ensure patency of the shunts.

Long-Term Follow-Up

The long-term follow-up was a standardized interview25 conducted by a physician not involved in the preor postoperative care of the patients. In cases of death, the date and cause were obtained from the county administrative board.

The ethics committee at Sahlgrenska Academy, University of Gothenburg, approved the study (S 596–3), and written informed consent was obtained from the patients or their next of kin.

Statistical Analysis

Changes in gait performance 3 and 6 months after shunt surgery were calculated as the mean percentage changes in the 6 variables, as compared with the preoperative values. Improvement was maximized to 100% so that single extreme values would not have a disproportional impact on the overall index. Psychometric improvement was calculated in the same manner from the 7 psychometric variables. Overall outcome was calculated as the mean of the gait and psychometric changes.

For descriptive statistics and correlations, the SPSS, version 16.0, statistical package (SPSS, Inc.) was used. The Mann-Whitney U-test was applied for group comparisons. Paired comparisons were performed using the Wilcoxon signed-rank test. Unless otherwise specified, a p < 0.05 was considered significant.

Results

Seven patients were randomized to a ligated shunt and 7 to an open shunt. All 14 patients were followed up at 3 months after surgery. The infusion studies at the 3-month follow-up confirmed that all open shunts were patent (Rout between 1.9 and 4.8 mm Hg/ml/min) and that all ligated shunts were nonfunctioning (unchanged Rout compared with preoperative values). Thirteen patients were followed up at 6 months after surgery. One patient with an open shunt at the 3-month follow-up suffered a major stroke between the 3- and 6-month follow-up and therefore was excluded from the 6-month follow-up.

Three-Month Follow-Up

The 7 patients with initially open shunts demonstrated improved psychometric performance by 23% and improved gait performance by 30%, and the total improvement was 26% (p < 0.05 for all; Fig. 2). The 7 patients with initially ligated shunts showed no changes in psychometric (1%), gait (0.4%), or overall outcomes (0.7%). Patients with open shunts improved significantly in their psychometric performance (p < 0.05) as compared with the patients with ligated shunts, although they improved only at a trend level in gait and overall performance (p < 0.1).

Fig. 2.
Fig. 2.

Graphs displaying individual treatment effect trajectories from the preoperative period to the 2 follow-up examinations. Left: Patients randomized to treatment with continuously open shunts. Right: Patients whose shunts were ligated during the first 3 months after surgery and then opened. mts = months.

Six-Month Follow-Up

The 6 patients randomized to open shunts retained improvement in psychometric (12%), gait (28%), and overall (23%) outcomes as compared with the preoperative values (p < 0.05 for all). The 7 patients whose shunts were opened after the 3-month follow-up improved in psychometric (18%), gait (28%), and overall (23%) outcomes as compared with preoperative values (p < 0.05 for all). Patients with initially ligated shunts improved significantly in psychometric, gait, and overall performance between the 3- and 6-month follow-up as compared with the patients with initially open shunts (p < 0.01). Improvement at the 6-month follow-up for all 13 patients was 16% in psychometric performance (p < 0.05), 28% in gait performance (p < 0.01), and 22% in overall outcome (p < 0.01).

Procedural Complications

Eight complications developed in 7 (50%) of the 14 patients. Five patients suffered from subdural hematomas; 1 hematoma was diagnosed at the 3-month follow-up and 4 at the 6-month follow-up. Two of the patients were medicated with acetylsalicylic acid. None of the patients with hematomas presented with headache, dizziness, or neurological deterioration during the study period. Four of the hematomas disappeared after upregulation of the Strata valve from a setting of 1.0 to 1.5 or 2.0. The fifth hematoma became symptomatic 7 months after shunt surgery. The patient in that case recovered completely after surgical evacuation of the hematoma.

Three patients suffered from ischemic stroke: 1 major and 2 minor. The major stroke occurred 4 months after surgery, and the patient in this case was the only one excluded from the 6-month follow-up because of severe deterioration. Minor ischemic events occurred between the 3- and 6-month follow-up: 1 patient with clinically diagnosed stroke showed no change on MR imaging studies, whereas the other patient presented without symptoms but with a new 10-mm lesion in the left internal capsule at the 6-month control MR imaging study. There was no infection and no obstruction of the shunts.

Long-Term Follow-Up

All 14 patients were contacted in February 2010. At that time, 3 had died and 1 was lost to follow-up. Causes of death were stroke, malignancy, and pneumonia.

The average follow-up time was 42 months (range 15–61 months). Five patients and 5 next of kin were interviewed.

Seven of the 10 patients felt better than they had before surgery. Six patients reported that they still had improved gait, and 5 that they still had mental improvements. Since the 6-month postoperative follow-up, the status of 6 patients had improved and 4 had deteriorated. Nine patients still lived in their own home without assistance (2 patients), with assistance from their spouses (3 patients), or with assistance from home help services (4 patients).

Discussion

To the best of our knowledge, this is the first randomized, double-blind placebo-controlled study showing that patients with iNPH symptoms improve in both cognitive and motor performance after ventriculoperitoneal shunt surgery. The rationale for the study was our clinical experience with patients exhibiting NPH symptoms, ventricular enlargement, and extensive white matter lesions that improved after shunt surgery despite low outflow resistance and no improvement following a CSF tap test.18,27 Thus, we chose to include only those cases normally diagnosed as questionable iNPH with severe white matter changes and no proven CSF dynamic disturbances or cases diagnosed as BD with ventricular enlargement.

In all controlled studies there is an ethical dilemma. Our main reason for performing the present study was the fact that these cases had no other effective treatment and that they might all benefit from a shunt 3 months after its placement. Unclipping the shunt tube and the infusion test studies were additional invasive procedures; however, these procedures were well tolerated and made it possible for us to be absolutely sure that a shunt was patent or closed.

To exclude patients with obvious CSF dynamic disturbances, we included only the patients with an Rout < 12 mm Hg/ml/min and no improvement after a 50-ml CSF tap test. High outflow resistance values correlate, in general, with good shunt surgery outcome in patients with iNPH.7 The cutoff level for shunt surgery is controversial and varies between 8 and 18 mm Hg/ml/min,7,10 with many centers using 12 mm Hg/ml/min. However, patients with outflow resistance below these levels might benefit from shunt surgery.7 The patients in this study had Rout values between 8.2 and 11.8 mm Hg/ml/min.

Like outflow resistance, the CSF tap test has both a high positive predictive value and a low negative predictive value.7,17,21 Patients included in the study would not have undergone surgery in many other centers given the normal results of the CSF dynamic tests. The 3-day external lumbar drainage test probably has a slightly better predictive value than the CSF tap test23 but is not routinely used in our department because of the higher costs and higher risk of complications as compared with the CSF tap test. It is challenging to classify the patients included in this study, which has an impact on the conclusions that can be drawn. If they are classified as having BD with ventricular enlargement, then the data point to a novel treatment. In our opinion, they could be classified as patients with atypical iNPH with an extensive vascular burden, who would qualify for shunt surgery.

Neuropathological studies have shown periventricular arteriosclerotic changes in both BD and iNPH.1 Patients with iNPH and BD exhibit similar MR imaging changes with the exception of a higher signal intensity in the periventricular region near the frontal horns in patients with NPH.26 We have found that deep white matter hyperintensities and subcortical lacunar infarctions are common findings in patients with NPH and are equally prevalent in shunt responders and nonresponders.27 Thus, BD and iNPH share a common pathophysiology, and the 2 disorders may even coexist in a single patient. It has been suggested that iNPH pathology may induce periventricular vascular changes24 or alternately that severe vascular pathology may cause a CSF dynamic disturbance in itself.

To evaluate the patients, we used quantitative psychometric and continuous gait tests to achieve the best possible statistical power. Since no scales were used and we currently have no method of quantifying urinary incontinence, we did not evaluate the effect on urinary incontinence. The use of several cognition and gait tests decreased the risk of a single test causing a false-negative or false-positive result.

Data in this study show that patients with iNPH improve in both motor and psychometric functions after shunt surgery despite an Rout < 12 mm Hg/ml/min and no response on a CSF tap test. The effectiveness of shunt surgery in the treatment of iNPH has been questioned by many authors14,15,28 and therefore controlled studies have been advocated. Our findings provide evidence for the effectiveness of shunt surgery in patients with iNPH. The degree of improvement after shunt surgery was the same order of magnitude as that frequently reported in other studies of patients with iNPH.11,25

However, the incidence of complications in this study indicates that the decision of whether to insert a shunt should be made with great caution. The occurrence of subdural hematomas could be explained by the chosen low opening pressure and might have been avoided with a higher opening pressure. We used the Strata valve with an integrated antisiphon device,20 and our rationale for the low pressure setting was to achieve good enough drainage to see a clinical effect. There are limited data regarding the consequences of selecting different opening pressures. Another factor that might have contributed to the development of subdural hematomas was that many patients were taking antiplatelet medication. We recommend a higher opening pressure for future studies in similar patients, which would probably reduce the number of subdural collections. However, the use of adjustable valves did make it possible to treat the overdrainage by upregulation of the valve resistance.

Three ischemic events also occurred during the study period. The patients had many vascular risk factors, and it is not possible to know if shunt surgery added to the risk of ischemic events. The standardized mortality rate in patients with iNPH is raised by a factor of 2.5 mostly because of cerebrovascular disease.25 A similar standardized mortality rate has been found in stroke patients,22,25 indicating that CSF diversion does not affect progressive vascular disease. The high number of cerebral insults during the study stresses that this patient group has severe comorbidity and that the risks of such complications must be considered prior to shunt surgery.

Another important factor in our study is the long-term result. We did not examine quality of life, but the self-reported improvement rate on an intention-to-treat basis was 50% after an average of 42 months. This result is similar to findings previously reported for patients with iNPH11,25 and speaks strongly in favor of shunt surgery provided that the number of complications can be reduced in future studies.

We originally planned to include 40 patients, but because some patients improved significantly and subdural hematomas were frequent, the steering committee decided to close the study when it was possible to achieve significant differences.

Conclusions

Patients with enlarged ventricles, extensive vascular white matter changes, and symptoms compatible with NPH showed improved motor and psychometric functions after shunt surgery despite an Rout < 12 mm Hg/ml/min and no response after a CSF tap test. These patients fulfilled the diagnostic criteria for both iNPH and BD.

Disclosure

This study was supported by unrestricted grants from the Edit Jacobson Foundation, the John and Britt Wennerström Foundation, and the Pfizer Foundation for clinical neurological research and the Per-Olof Ahl Foundation for research on vascular diseases of the brain.

Author contributions to the study and manuscript preparation include the following. Conception and design: all authors. Acquisition of data: all authors. Analysis and interpretation of data: all authors. Drafting the article: all authors. Critically revising the article: all authors. Reviewed final version of the manuscript and approved it for submission: all authors. Statistical analysis: Tisell, Tullberg, Hellström, Wikkelsö. Study supervision: Wikkelsö.

Acknowledgment

The authors thank Dr. Katrin Rabie for performing the long-term follow-up.

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    Tullberg MHultin LEkholm SMånsson JEFredman PWikkelsø C: White matter changes in normal pressure hydrocephalus and Binswanger disease: specificity, predictive value and correlations to axonal degeneration and demyelination. Acta Neurol Scand 105:4174262002

  • 27

    Tullberg MJensen CEkholm SWikkelsø C: Normal pressure hydrocephalus: vascular white matter changes on MR images must not exclude patients from shunt surgery. AJNR Am J Neuroradiol 22:166516732001

  • 28

    Vanneste JA: Diagnosis and management of normal-pressure hydrocephalus. J Neurol 247:5142000

  • 29

    Wahlund LOBarkhof FFazekas FBronge LAugustin MSjögren M: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:131813222001

  • 30

    Wikkelsø CAndersson HBlomstrand CLindqvist G: The clinical effect of lumbar puncture in normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry 45:64691982

Article Information

Address correspondence to: Magnus Tisell, M.D., Ph.D., Department of Neurosurgery, Vån 5, Blå stråket 7, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden. email: magnus.tisell@vgregion.se.

Please include this information when citing this paper: published online January 14, 2011; DOI: 10.3171/2010.11.JNS10967.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Two FLAIR MR images showing white matter disease (Wahlund Score 3) and ventriculomegaly.

  • View in gallery

    Graphs displaying individual treatment effect trajectories from the preoperative period to the 2 follow-up examinations. Left: Patients randomized to treatment with continuously open shunts. Right: Patients whose shunts were ligated during the first 3 months after surgery and then opened. mts = months.

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Tullberg MJensen CEkholm SWikkelsø C: Normal pressure hydrocephalus: vascular white matter changes on MR images must not exclude patients from shunt surgery. AJNR Am J Neuroradiol 22:166516732001

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Vanneste JA: Diagnosis and management of normal-pressure hydrocephalus. J Neurol 247:5142000

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Wahlund LOBarkhof FFazekas FBronge LAugustin MSjögren M: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:131813222001

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Wikkelsø CAndersson HBlomstrand CLindqvist G: The clinical effect of lumbar puncture in normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry 45:64691982

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