Department of Neurosurgery, Shinko Hospital, Kobe, Japan

CLINICAL ARTICLE J Neurosurg 127:1436 1442, 2017 Utility of MRI-based disproportionately enlarged subarachnoid space hydrocephalus scoring for predicting prognosis after surgery for idiopathic normal pressure hydrocephalus: clinical research *Narihide Shinoda, MD, Osamu Hirai, MD, Shinya Hori, MD, Kazuyuki Mikami, MD, Toshiaki Bando, MD, Daisuke Shimo, MD, Takahiro Kuroyama, MD, Yoji Kuramoto, MD, Masato Matsumoto, MD, and Yasushi Ueno, MD Department of Neurosurgery, Shinko Hospital, Kobe, Japan OBJECTIVE The presence of disproportionately enlarged subarachnoid space hydrocephalus (DESH) on brain imaging is a recognized finding of idiopathic normal pressure hydrocephalus (inph), but the features of DESH can vary across patients. The aim of this study was to evaluate the utility of MRI-based DESH scoring for predicting prognosis after surgery. METHODS In this single-center, retrospective cohort study, the DESH score was determined by consensus between a group of neurosurgeons, neurologists, and a neuroradiologist based on the preoperative MRI findings of the patients with suspected inph. The DESH score was composed of the following 5 items, each scored from 0 to 2 (maximum score 10 points): ventriculomegaly, dilated sylvian fissures, tight high convexity, acute callosal angle, and focal sulcal dilation. The association between the DESH score and improvement of the scores on the modified Rankin Scale (mrs), inph Grading Scale (inphgs), Mini Mental State Examination (MMSE), Trail Making Test-A (TMT-A), and Timed 3-Meter Up and Go Test (TUG-t) was examined. The primary end point was improvement in the mrs score at 1 year after surgery, and the secondary outcome measures were the inphgs, MMSE, TMT-A, and TUG-t scores at 1 year after surgery. Improvement was determined as improvement of 1 or more levels on mrs, 1 point on inphgs, 3 points on MMSE, a decrease of > 30% on TMT-A, and a decrease of > 10% on TUG-t. RESULTS The mean DESH score for the 50 patients (mean age 77.6 ± 5.9 years) reviewed in this study was 5.58 ± 2.01. The mean rate of change in the mrs score was -0.50 ± 0.93, indicating an inverse correlation between the DESH score and rate of change in the mrs score (r = -0.749). Patients who showed no improvement in mrs score tended to have a low DESH score as well as low preoperative MMSE and TMT-A scores. There were no differences in the areas of deep white matter hyperintensity and periventricular hyperintensity on the images between patients with and without an improved mrs score (15.6% vs 16.7%, respectively; p = 1.000). The DESH score did differ significantly between patients with and without improved scores on the inphgs (6.39 ± 1.76 vs 4.26 ± 1.69, respectively; p < 0.001), MMSE (6.63 ± 1.82 vs 5.09 ± 1.93; p = 0.010), TMT-A (6.32 ± 1.97 seconds vs 5.13 ± 1.93 seconds; p = 0.042), and TUG-t (6.48 ± 1.81 seconds vs 4.33 ± 1.59 seconds; p < 0.001). CONCLUSIONS MRI-based DESH scoring is useful for the prediction of neurological improvement and prognosis after surgery for inph. https://thejns.org/doi/abs/10.3171/2016.9.jns161080 KEY WORDS idiopathic normal pressure hydrocephalus, disproportionately enlarged subarachnoid space hydrocephalus, SINPHONI trial, ventriculoperitoneal shunt, DESH score ABBREVIATIONS DESH = disproportionately enlarged subarachnoid space hydrocephalus; inph = idiopathic normal pressure hydrocephalus; inphgs = inph Grading Scale; MMSE = Mini-Mental State Examination; mrs = modified Ranking Scale; SINPHONI = Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement; TMT-A = Trail Making Test-A; TUG-t = Timed 3-Meter Up and Go Test. SUBMITTED April 26, 2016. ACCEPTED September 19, 2016. INCLUDE WHEN CITING Published online February 3, 2017; DOI: 10.3171/2016.9.JNS161080. * Drs. Shinoda and Hirai contributed equally to this work. 1436 AANS, 2017

Utility of the MRI-based DESH score for postoperative inph prognosis Idiopathic normal pressure hydrocephalus (inph), a treatable syndrome in the elderly, is characterized by the classic triad of gait disturbance, dementia, and urinary disturbance. 2 Kitagaki et al. 10 first reported the appearance of disproportionately enlarged subarachnoid space hydrocephalus (DESH) on brain imaging in 1988, and DESH is now a recognized characteristic feature of inph and itself composed of the findings of ventriculomegaly, dilated sylvian fissures, tight high convexity, acute callosal angle, and focal sulcal dilation. 1,6,8,10 In the Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement (SINPHONI) trial, the diagnosis of idiopathic normal pressure hydrocephalus is supported by an MRI-based scheme, and DESH was shown on MRI to have a high positive predictive value in identifying shunt-responsive inph patients. 6 Most cases of inph have characteristic imaging findings of DESH, but a subgroup of patients has much less typical DESH findings, 17 and therefore the prognostic difference according to the nature of the imaging findings is unclear. Hashimoto et al. 6 demonstrated that the MRI features of DESH namely, ventriculomegaly, tight high-convexity and medial subarachnoid spaces, and enlarged sylvian fissures are useful for the diagnosis of inph, but they did not describe other features, particularly the callosal angle and focal sulcal dilation. Furthermore, they did not explain the prognostic difference separated by the degree of the MRI features of DESH (e.g., more typical DESH findings, better outcome). In this study, we quantitatively evaluated the appearance of DESH on MRI prior to surgery in elderly patients with inph and investigated if the resulting DESH score was useful for predicting neurological improvement and prognosis. The principal utility of this study is the potential to develop a noninvasive and easy method for predicting response to CSF diversion in patients with inph. Methods Study Design Patients with suspected inph defined as the presence of 1 or more symptoms of the classic triad of gait disturbance, cognitive impairment, and urinary symptoms underwent MRI. The resulting images were reviewed by a group of neurosurgeons, neurologists, and a neuroradiologist, who assigned a DESH score that was reached by consensus. When their opinions were divided, they discussed it again and adopted the opinion of the majority. By separating the raters and the operating surgeon, there were no factors that influenced the data. DESH Score The DESH score was composed of the following 5 items, each scored from 0 to 2 (maximum score 10): ventriculomegaly, dilated sylvian fissures, tight high convexity, acute callosal angle, and focal sulcal dilation (Table 1). TABLE 1. Summarized DESH scales Grade Definition Ventriculomegaly 0 Normal (Evans index <0.3) 1 Slight dilatation (Evans index 0.3 & 0.35) 2 Dilatation (Evans index >0.35) Dilated sylvian fissures 0 Normal or narrow 1 Slight dilatation or unilateral 2 Bilateral dilatation Tight high convexity 0 Normal or wider than normal 1 Slight compression 2 Definitive compression Acute callosal angle 0 Obtuse angle (>100 ) 1 Not acute, but not obtuse angle ( 90 & 100 ) 2 Acute angle (<90 ) Focal sulcal dilation 0 Not present 1 Some present 2 Many present Ventriculomegaly The Evans index was measured on transverse images as the ratio between the maximum diameter of the frontal horns of the lateral ventricles and the maximum inner diameter of the skull in the same section. 21 Ventriculomegaly was graded as follows: 0, normal (Evans index < 0.3); 1, slight dilation (Evans index 0.3 0.35); or 2, dilation (Evans index > 0.35). Dilated Sylvian Fissures The coronal images used for the sylvian fissure ordinal were reconstructed at the level of the central part of the brainstem and angulated along the brainstem. 25 Dilation was graded as follows: 0, normal or narrow; 1, slight dilation or unilateral; or 2, bilateral dilation. Tight High Convexity Tight high convexity was evaluated on coronal and transverse images and graded as follows 20 0, normal or wider than normal; 1, slight compression; or 2, definitive compression. Acute Callosal Angle The callosal angle measured on a coronal MR image is the angle between the lateral ventricles through the posterior commissure and perpendicular to the anteriorposterior commissure plane. 8,9 The angle was graded as 0, obtuse (> 100 ); 1, not acute or obtuse (90 100 ); or 2, acute (< 90 ). Focal Sulcal Dilation The accumulation of CSF in focally enlarged sulci, which has previously been referred to as transport sulci, was graded as follows 7,26 0, no sulci; 1, some sulci present; or 2, many sulci present. Regardless of a high or low DESH score, patients were 1437

N. Shinoda et al. included in the study if they satisfied the inclusion criteria stated below. Participants and Protocol The study was approved by the institutional review board and adhered to the principles set forth in the Declaration of Helsinki. It was performed as a retrospective, single-center cohort study to examine the 1-year outcome in inph patients who received a ventriculoperitoneal shunt with the Codman-Hakim programmable valve (CSF shunt valve, Codman, a Johnson & Johnson Co.) at our institution between April 2007 and March 2016. The initial pressure for the shunt system was set according to the patient s height and body mass index based on the estimated hydrostatic pressure and intraabdominal pressure. 14,15 The criteria for patient selection were determined in reference to the SINPHONI trial. 6 The inclusion criteria were as follows: 1) age 60 years or older; 2) presence of 1 or more symptoms of the triad (gait disturbance, cognitive impairment, and urinary symptoms), which were measurable on inphgs 13 ; 3) MRI features of inph, with ventriculomegaly indicated by an Evans index score of > 0.3 on MRI 11 ; 4) the absence of known disorders causing ventriculomegaly; 5) normal CSF content (protein 50 mg/dl and cell count 3 cells/ml) and pressure ( 20 cm H 2 O); and 6) positive response on the CSF tap test. 24 The exclusion criteria were: 1) the presence of a musculoskeletal, cardiopulmonary, renal, hepatic, or mental disorder that would make it difficult to evaluate changes in symptoms; 2) obstacles to 1-year follow-up; and 3) bleeding diathesis or taking anticoagulant medication. In addition, we performed SPECT in patients with a Mini Mental State Examination (MMSE) score of less than 20 and excluded other differential diseases, including Alzheimer s disease. Outcome Measures According to both the inph guidelines 19 and Guideline for management of idiopathic normal pressure hydrocephalus: second edition, 16 improvement was determined as improvement of 1 or more levels on mrs, 1 points on the inph grading scale, 3 points on MMSE, a decrease of greater than 30% on TMT-A, and a decrease of greater than 10% on TUG-t. The primary end point was improvement in the mrs score 23 at 1 year after surgery, and the secondary outcome measures were the inphgs, 27 MMSE, 4 TMT-A, 5 and TUG-t 18 scores at 1 year after surgery. We examined the association between the DESH score and an improved score for these 5 measures at 1 year after surgery. In addition, we investigated leukoaraiosis on MR images, deep white matter hyperintensity, and periventricular hyperintensity, which are reported to be associated with the risk factors for vascular diseases such as hypertension and smoking. 3,12 Statistical Analysis The analysis was performed using R statistical software (Foundation for Statistical Computing). Statistical significance was examined using the Student t-test, and the correlation coefficients were tested using Microsoft Excel (version 2016; Microsoft Corp.). Results Patient Population The flow chart for this study is shown in Fig. 1. Of the 110 preregistered patients, 10 patients had a diagnosis of Alzheimer s disease or other disease as determined by SPECT and assessment of cognitive function, and 45 patients did not fulfill the CSF inclusion criteria or had positive findings on a tap test. Of the 55 patients who proceeded to registration, 5 withdrew (1 patient each due to traumatic intracranial hemorrhage, acute ischemic stroke, or aggravation of cirrhosis, and 2 patients were lost to follow-up), leaving 50 patients for analysis. Baseline Data The baseline data for the 50 patients are summarized in Table 2. Almost all patients were older than 70 years of age (mean age 77.6 ± 5.9 years [± SD]). The objective symptoms on inphgs were gait disturbance in 94% patients, cognitive impairment in 82% of patients, urinary symptoms in 64% of patients, and the classic triad in 48% of patients. On MRI review, the Evans index typically demonstrated a slight dilation (Evans index 0.3 0.35), and, in most cases, the callosal angle was 100. The mean DESH score was 5.58 ± 2.01 (range 2 10) and showed a normal distribution (Fig. 2). Clinical Outcomes The mean initial valve pressure of the ventriculoperitoneal shunt was 14.5 ± 3.5 cm H 2 O, and 8 patients needed TABLE 2. Background characteristics and preoperative status of 50 patients with suspected inph Characteristic Value Demographics Mean age, yrs 77.6 ± 5.9 (61 87) Male sex 33 (66) Symptoms present Triad of symptoms 24 (48) Gait + cognitive impairment 13 (26) Gait + urinary symptom 6 (12) Cognitive impairment + urinary symptom 2 (4) Gait impairment only 4 (8) Cognitive impairment only 2 (4) Urinary symptom only 0 Lumbar puncture finding Mean CSF pressure, cm H 2 O 13.3 ± 1.92 (10.0 17.5) MRI findings Mean Evans index, % 33.2 ± 2.8 Mean callosal angle, 91.7 ± 13.1 Mean DESH score 5.58 ± 2.01 Data are presented as the mean ± SD (range) or number (%) of patients. 1438

Utility of the MRI-based DESH score for postoperative inph prognosis FIG. 1. Flow chart for this study from the initial screening to the final analysis. to have the pressure readjusted throughout the follow-up period. At 1 year after surgery, the mean mrs score improved from 2.54 ± 0.76 to 2.02 ± 1.17 (p = 0.010). The improvement rate defined as a 1 or more levels of improvement on mrs was 64.0%, and the mean rate of change in the mrs score was 0.50 ± 0.93 (range 2 to 2) (Fig. 3A and B), indicating an inverse correlation between the DESH score and the rate of change in the mrs score (r = -0.749; Fig. 4). FIG. 2. Distribution map of the DESH scores. 1439

N. Shinoda et al. FIG. 3. Distribution maps of the mrs scores before and 1 year after surgery (A) and the rate of change in mrs scores (B). Table 3 compares the preoperative scores between the patients with an improved mrs score (n = 32; 64.0%) and those without an improved mrs score (n = 18; no change in 10 patients and aggravation in 8 patients). There were marked significant differences between patients with and without improvement in relation to the DESH score (6.50 ± 2.0 vs 3.94 ± 1.5, respectively; p < 0.001) and preoperative MMSE score (23.7 ± 3.5 vs 17.7 ± 3.0; p < 0.001), as well as a difference in the preoperative TMT-A score (159.5 ± 49.2 vs 212.0 ± 51.8; p = 0.020). On the other hand, no differences were found in relation to leukoaraiosis on the MR images between patients with and without improved mrs scores (15.6% vs 16.7%; p = 1.000). Thus, patients with an improved mrs score tended to have low preoperative DESH, MMSE, and TMT-A scores. All the secondary outcomes showed significant improvement at 1 year after surgery (Table 4). The mean inphgs score improved from 6.00 ± 1.93 to 5.00 ± 2.85 (p = 0.043), MMSE improved from 21.54 ± 4.02 to 23.38 ± 4.53 (p = 0.047), TMT-A improved from 178.4 ± 69.4 seconds to 134.3 ± 59.8 seconds (p = 0.049), and TUG-t improved from 27.5 ± 11.3 seconds to 21.1 ± 10.1 seconds (p = 0.046). As for the overall improvements after surgery, 62.0% of patients had an improved inphgs score of 1 or higher, 32.0% had an improved MMSE score of 3 or higher, 30% had a decreased TMT-A time, and 58.0% had FIG. 4. Inverse correlation between DESH score and the rate of change in mrs score (r = -0.749). a greater than 10% decrease on TUG-t. Furthermore, there was a significant difference in the DESH score between patients with and without an improved inphgs score (DESH score 6.39 ± 1.76 vs 4.26 ± 1.69; p < 0.001), MMSE (DESH score 6.63 ± 1.82 vs 5.09 ± 1.93; p = 0.010), TMT- A (DESH score 6.32 ± 1.97 vs 5.13 ± 1.93; p = 0.042), and TUG-t (DESH score 6.48 ± 1.81 vs 4.33 ± 1.59; p < 0.001) (Table 5). Based on these findings, the DESH score appears to have a strong association with the mrs, inphgs, MMSE, TMT-A, and TUG-t scores. Discussion The improvement rate of 1 or more levels on mrs was 64.0% in our cohort, which is similar to the rate of 69.0% reported by the SINPHONI trial. 6 Our findings suggest that a high DESH score has an important positive predictive value in relation to neurological improvement after surgery for inph, in turn suggesting that MRI-based DESH scoring has diagnostic utility. A previous multicenter, prospective cohort study found an MRI-based diagnostic scheme highly useful and concluded that the DESH sign tight high convexity, medial TABLE 3. Comparison of preoperative scores between patients with and without an improved mrs score after surgery Variable Improvement in mrs Score (n = 32) No Improvement in mrs Score (n = 18)* p Value DESH score 6.50 ± 2.0 3.94 ± 1.5 <0.001 inphgs score 5.68 ± 2.13 6.56 ± 2.35 0.066 MMSE score 23.7 ± 3.5 17.7 ± 3.0 <0.001 TMT-A, sec 159.5 ± 49.2 212.0 ± 51.8 0.020 TUG-t, sec 27.0 ± 8.3 28.4 ± 7.1 0.649 DWMH or PVH on MRI 5 (15.6) 3 (16.7) 1.000 DWMH = deep white matter hyperintensity; PVH = periventricular hyperintensity. Data are presented as the mean ± SD or number (%) of patients. * No change was observed in 10 patients, and aggravation was observed in 8 patients. Determined using the Student t-test. Determined using the Fisher exact test. 1440

Utility of the MRI-based DESH score for postoperative inph prognosis TABLE 4. Comparison of secondary outcomes between preoperative status and 1-year postoperative status Variable Before Surgery 1 Yr After Surgery p Value* inphgs score 6.00 ± 1.93 5.00 ± 2.85 0.043 MMSE score 21.54 ± 4.02 23.38 ± 4.53 0.047 TMT-A, secs 178.4 ± 69.4 134.3 ± 59.8 0.049 TUG-t, secs 27.5 ± 11.3 21.1 ± 10.1 0.046 Data are shown as the mean ± SD. * p values were calculated using the Student t-test. subarachnoid spaces, and enlarged sylvian fissures with ventriculomegaly is valuable for the diagnosis of inph. 6 We assigned the DESH score on the basis of 5 parameters, each of which was scored simply from 0 to 2 for a maximum of 10 points: ventriculomegaly, dilated sylvian fissures, tight high convexity, acute callosal angle, and focal sulcal dilation. These 5 features mentioned above are very important in diagnosing inph, but we must be aware of their correlations. Ishii et al. 9 reported that the Evans index correlated well with the relative volume of the enlarged ventricle systems and sylvian fissures, and it correlated inversely with the relative volume of the sulci at the high convexity and midline. The callosal angle also showed a good negative correlation with the relative volume of the ventricle systems and sylvian fissures, and it correlated positively with the relative volume of the sulci at the high convexity and midline. In addition, Virhammar et al. 25 reported that the callosal angle correlated with focal sulcal dilation (r = -0.28), and they concluded that a small callosal angle, wide temporal horns, and the occurrence of disproportionately enlarged subarachnoid space hydrocephalus were significant predictors of a positive shunt outcome. In our study, leukoaraiosis was not related to improvement after surgery. A previous study showed that this parameter was a negative factor associated with the clinical improvement of inph; 21 however, a recent study reported that patients must not be excluded from shunt surgery on the basis of leukoaraiosis findings because patients with severe leukoaraiosis had a positive outcome rate similar to that of the entire sample. 22 There may be room for debate about this result, but the presence of leukoaraiosis on MRI does not predict a poor outcome of surgery and therefore should be used as an exclusion criterion for shunting. Our study examined both the usefulness of the DESH score that followed an MRI-based diagnostic scheme and the beneficial effect of shunt surgery on inph after 1 year. The diagnosis of inph is established in terms of response to surgery, and the efficacy of surgery depends on the diagnostic accuracy. 6 Therefore, the more accurate the diagnosis is, the more efficacious the treatment will be. Our study suggests a strong association between the DESH score and prognosis after surgery. MRI-based DESH scoring appears to be a useful objective method as it allows an easy and quantitative evaluation for predicting prognosis. Limitations These enrollment criteria were based solely on the SINPHONI trial. 6 This study was a single-center, retrospective cohort study, and it was exploratory. So we will TABLE 5. Comparison of the DESH scores between patients with and without improved scores after surgery Test No. of Patients (n = 50) DESH Score* p Value inphgs Improvement 31 6.39 ± 1.76 <0.001 No improvement 19 4.26 ± 1.69 MMSE Improvement 16 6.63 ± 1.82 0.010 No improvement 34 5.09 ± 1.93 TMT-A Improvement 15 6.32 ± 1.97 0.042 No improvement 35 5.13 ± 1.93 TUG-t Improvement 29 6.48 ± 1.81 <0.001 No improvement 21 4.33 ± 1.59 * Data are presented as the mean ± SD. p values were calculated using the Student t-test. need to conduct a prospective investigation to confirm the accuracy of our results. The cohort was relatively small because of the strict differential diagnosis and the robust inclusion criteria we used before registration by assessing cognitive function and performing SPECT. However, this is the first study to evaluate the utility of MRI-based DESH scoring for predicting prognosis after surgery, and it suggests the method is promising and that further study is warranted. Conclusions A typical, high DESH score had a positive predictive value for neurological improvement after surgery for inph. The DESH score does appear to be useful for the prediction of neurological improvement and prognosis after surgery. References 1. Adachi M, Kawanami T, Ohshima F, Kato T: Upper midbrain profile sign and cingulate sulcus sign: MRI findings on sagittal images in idiopathic normal-pressure hydrocephalus, Alzheimer s disease, and progressive supranuclear palsy. Radiat Med 24:568 572, 2006 2. Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH: Symptomatic occult hydrocephalus with normal cerebrospinal-fluid pressure: a treatable syndrome. N Engl J Med 273:117 126, 1965 3. Bradley WG Jr, Whittemore AR, Watanabe AS, Davis SJ, Teresi LM, Homyak M: Association of deep white matter infarction with chronic communicating hydrocephalus: implications regarding the possible origin of normal-pressure hydrocephalus. AJNR Am J Neuroradiol 12:31 39, 1991 4. Folstein MF, Folstein SE, McHugh PR: Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189 198, 1975 5. Gordon NG: The Trail Making Test in neuropsychological diagnosis. J Clin Psychol 28:167 169, 1972 6. Hashimoto M, Ishikawa M, Mori E, Kuwana N: Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study. Cerebrospinal Fluid Res 7:18, 2010 7. Holodny AI, George AE, de Leon MJ, Golomb J, Kalnin AJ, 1441

N. Shinoda et al. Cooper PR: Focal dilation and paradoxical collapse of cortical fissures and sulci in patients with normal-pressure hydrocephalus. J Neurosurg 89:742 747, 1998 8. Ishii K, Kanda T, Harada A, Miyamoto N, Kawaguchi T, Shimada K, et al: Clinical impact of the callosal angle in the diagnosis of idiopathic normal pressure hydrocephalus. Eur Radiol 18:2678 2683, 2008 9. Ishii K, Soma T, Shimada K, Oda H, Terashima A, Kawasaki R: Automatic volumetry of the cerebrospinal fluid space in idiopathic normal pressure hydrocephalus. Dement Geriatr Cogn Dis Extra 3:489 496, 2013 10. Kitagaki H, Mori E, Ishii K, Yamaji S, Hirono N, Imamura T: CSF spaces in idiopathic normal pressure hydrocephalus: morphology and volumetry. AJNR Am J Neuroradiol 19:1277 1284, 1998 11. Klinge P, Marmarou A, Bergsneider M, Relkin N, Black PM: Outcome of shunting in idiopathic normal-pressure hydrocephalus and the value of outcome assessment in shunted patients. Neurosurgery 57 (3 Suppl):S40 S52, ii v, 2005 12. Krauss JK, Droste DW, Vach W, Regel JP, Orszagh M, Borremans JJ, et al: Cerebrospinal fluid shunting in idiopathic normal-pressure hydrocephalus of the elderly: effect of periventricular and deep white matter lesions. Neurosurgery 39:292 300, 1996 13. Kubo Y, Kazui H, Yoshida T, Kito Y, Kimura N, Tokunaga H, et al: Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus. Dement Geriatr Cogn Disord 25:37 45, 2008 14. Miyake H, Kajimoto Y, Tsuji M, Ukita T, Tucker A, Ohmura T: Development of a quick reference table for setting programmable pressure valves in patients with idiopathic normal pressure hydrocephalus. Neurol Med Chir (Tokyo) 48:427 432, 2008 15. Miyake H, Ohta T, Kajimoto Y, Nagao K: New concept for the pressure setting of a programmable pressure valve and measurement of in vivo shunt flow performed using a microflowmeter. Technical note. J Neurosurg 92:181 187, 2000 16. Mori E, Ishikawa M, Kato T, Kazui H, Miyake H, Miyajima M, et al: Guideline for management of idiopathic normal pressure hydrocephalus: second edition. Neurol Med Chir (Tokyo) 52:775 809, 2012 17. Mostafa T, Craven C, Patel NA, Dyson EW, Matloob SA, Chari A et al: DESH negative normal pressure hydrocephalus: can patients still benefit from shunt insertion? Fluids Barriers CNS 12 (Suppl 1):O52, 2015 18. Podsiadlo D, Richardson S: The timed Up & Go : a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39:142 148, 1991 19. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM: Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 57 (3 Suppl):S4 S16, ii v, 2005 20. Sasaki M, Honda S, Yuasa T, Iwamura A, Shibata E, Ohba H: Narrow CSF space at high convexity and high midline areas in idiopathic normal pressure hydrocephalus detected by axial and coronal MRI. Neuroradiology 50:117 122, 2008 21. Toma AK, Holl E, Kitchen ND, Watkins LD: Evans index revisited: the need for an alternative in normal pressure hydrocephalus. Neurosurgery 68:939 944, 2011 22. Tullberg M, Jensen C, Ekholm S, Wikkelsø C: Normal pressure hydrocephalus: vascular white matter changes on MR images must not exclude patients from shunt surgery. AJNR Am J Neuroradiol 22:1665 1673, 2001 23. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J: Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:604 607, 1988 24. Virhammar J, Cesarini KG, Laurell K: The CSF tap test in normal pressure hydrocephalus: evaluation time, reliability and the influence of pain. Eur J Neurol 19:271 276, 2012 25. Virhammar J, Laurell K, Cesarini KG, Larsson EM: Preoperative prognostic value of MRI findings in 108 patients with idiopathic normal pressure hydrocephalus. AJNR Am J Neuroradiol 35:2311 2318, 2014 26. Wikkelsö C, Andersson H, Blomstrand C, Matousek M, Svendsen P: Computed tomography of the brain in the diagnosis of and prognosis in normal pressure hydrocephalus. Neuroradiology 31:160 165, 1989 27. Zemack G, Romner B: Adjustable valves in normal-pressure hydrocephalus: a retrospective study of 218 patients. Neurosurgery 51:1392 1402, 2002 Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author Contributions Conception and design: Shinoda. Acquisition of data: Shinoda. Analysis and interpretation of data: Shinoda, Hirai. Drafting the article: Shinoda. Critically revising the article: Shinoda. Reviewed submitted version of manuscript: Shinoda. Approved the final version of the manuscript on behalf of all authors: Shinoda. Statistical analysis: Shinoda. Administrative/technical/material support: all authors. Study supervision: Hirai, Ueno. Correspondence Narihide Shinoda, Department of Neurosurgery, Shinko Memorial Hospital, 1-4-47 Wakinohama-cho, Chuo-ku, Kobe, Hyogo 651-0072, Japan. email: shinoda.narihide@shinkohp.or.jp. 1442