Neurosurgery Blog


Daily bibliographic review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

Cost-effectiveness analysis of shunt surgery for idiopathic normal pressure hydrocephalus

Acta Neurochir (2017) 159:995–1003

We showed that ventriculoperitoneal (VP) shunt and lumboperitoneal (LP) shunt surgeries are beneficial for patients with idiopathic normal pressure hydrocephalus (iNPH) in the Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement (SINPHONI; a multicenter prospective cohort study) and in SINPHONI-2 (a multicenter randomized trial). Although therapeutic efficacy is important, cost-effectiveness analysis is equally valuable.

Methods Using both a set of assumptions and using the data from SINPHONI and SINPHONI-2, we estimated the total cost of treatment for iNPH, which consists of medical expenses (e.g., operation fees) and costs to the long-term care insurance system (LCIS) in Japan. Regarding the natural course of iNPH patients, 10% or 20% of patients on each modified Rankin Scale (mRS) show aggravation (aggravation rate: 10% or 20%) every 3 months if the patients do not undergo shunt surgery, as described in a previous report. We performed cost-effectiveness analyses for the various scenarios, calculating the quality-adjusted life year (QALY) and the incremental cost-effective ratio (ICER). Then, based on the definition provided by a previous report, we assessed the cost-effectiveness of shunt surgery for iNPH.

Results In the first year after shunt surgery, the ICER of VP shunt varies from 29,934 to 40,742 USD (aggravation rate 10% and 20%, respectively) and the ICER of LP shunt varies from 58,346 to 80,392 USD (aggravation rate 10% and 20%, respectively), which indicates that the shunt surgery for iNPH is a cost-effective treatment. In the 2nd postoperative year, the cost to the LCIS will continue to decrease because of the lasting improvement of the symptoms due to the surgery. The total cost for iNPH patients will show a positive return on investment in as soon as 18 months (VP) and 21 months (LP), indicating that shunt surgery for iNPH is a cost-effective treatment.

Conclusions Because the total cost for iNPH patients will show a positive return on investment within 2 years, shunt surgery for iNPH is a cost-effective treatment and therefore recommended. The SINPHONI-2 study was registered with the University Hospital Medical Information Network Clinical Trials registry: UMIN000002730) SINPHONI was registered with, no. NCT00221091.

Shunting of the over 80s in normal pressure hydrocephalus

Acta Neurochir (2017) 159:987–994

Idiopathic normal pressure hydrocephalus is predominantly a disease of the elderly. By its nature, many of those who present to clinic are in advanced old age with multiple comorbidities. Majority of patients treated are younger than 80 years old. We present the clinical outcomes and complication rates of patients over the age of 80 years at the time of operation, during the past 11 years at a single institution.

Methods Retrospective analysis of clinical records of all patients over the age of 80 years, who presented to our institution between 2006 and 2016.

Results were analysed for co-morbidities, immediate and delayed complications, change in mobility/cognitive function post shunting of hydrocephalus.

Results 39 patients (24 male, 15 female) met criteria. Mean [SD] age at the time of shunt insertion was 84 years (+/− 3.22) (range 80–94). No patients developed immediate CSF infection or sub-dural collection, or extended length of stay due to surgical or anaesthetic complications. There were no perioperative or anaesthetic complications. 4 patients required a delayed surgical revision to encourage greater CSF drainage. 3 patients went on to develop delayed subdural haematoma, 1 of which was associated with trauma, 2 through overdrainage. 1 patient experienced poor post-operative wound healing and subsequently underwent removal of shunt. Of the 34 patient followed up, 27 patients (79.4%) improved in their mobility. (64.7%) patients/families reported symptomatic improvement in their cognition and memory. 6 (17.7%) patients did not experience an improvement in either mobility or cognitive function.

Conclusions Our data supports the assertion that, with proper patient selection, shunting of the over 80s with iNPH is a safe and effective procedure.

Low-pressure Hydrocephalus in Children

Neurosurgery 80:439–447, 2017

Low-pressure hydrocephalus (LPH) is a rare phenomenon characterized by a clinical picture consistent with elevated intracranial pressure (ICP) and ventricular enlargement, but also a well-functioning shunt and low or negative ICP.

OBJECTIVE: To report our experience in evaluating this challenging problem. METHODS: Patients with LPH were identified from several sources, including institutional procedural databases and personal case logs. Electronic medical records were reviewed to collect demographic, clinical, surgical, and radiographic data to determine the presence of LPH. Each patient’s clinical course, including presentation, management, and outcome, is reported.

RESULTS: Thirty instances of LPH were identified in 29 patients. Eleven cases (37.9%) of LPH were after lumbar puncture (LP), and 19 cases (62.1%) occurred without any preceding spinal procedure. Among the post-LP patients, conservative measures alone were successful in 3 cases (27%); lumbar blood patch was successful in 2 cases (18%); and 6 cases (55%) required external cerebrospinal fluid (CSF) drainage. Of the spontaneous cases, 5 patients did not receive the full spectrum of treatment because of terminal prognosis. Of the remaining 14 patients, 11 (78.6%) required external CSF drainage. Post-LP patients required fewer days of external CSF drainage (median, 4 [range, 0-12] vs median, 11 [range, 0-90]) and had a shorter hospital stay (median, 2 [range, 2-16] vs median, 8 [range, 0-26]).

CONCLUSION: This study represents the largest series of LPH. Although its pathophysi-ology remains a mystery, there are a variety of management options. Multiple procedures and a protracted hospital stay are often required to successfully treat LPH.


Contrast-enhanced shunt series (“shuntography”) compare favorably to other shunt imaging modalities in detecting shunt occlusion

Acta Neurochir (2017) 159:63–70

Obstruction is a common cause of ventriculo-peritoneal shunt failure. Head computed tomography and plain x-ray examinations of shunt tubing (“shunt series”) are routinely used in patients readmitted for reemerging symptoms but are of limited value. The validity of shunt series can be improved by applying contrast agent into the system (contrast-enhanced shunt series, a.k.a. a “shuntogram” or “shuntography”). We hypothesized that contrast-enhanced shunt series have a high predictive value for shunt revision surgeries.

Methods: We retrospectively re-evaluated 107 contrast-enhanced shunt series and reviewed the patient histories. We defined outcome parameters for calculating the utility of a pathological contrast-enhanced shunt series in predicting revision surgery.

Results: Of 107 contrast-enhanced shunt series, 41 examinations were positive for obstruction, mainly of the ventricular (36.5 %) and the peritoneal catheter (48.8 %). Within 30 days, 35 successful revision surgeries and 3 revision surgeries without resolution of symptoms were performed. In two cases the shunt tubing was found to be patent. Sixty-six negative examinations resulted in two revision surgeries, in addition to ten surgeries not attempting to restore patency. After 30 days, the specificity of contrast-enhanced shunt series for shunt failure identification was calculated at 92.8 %, the sensitivity at 94.7 %, the positive predictive value at 87.8 %, and the negative predictive value at 97.0 %.

Conclusions: The contrast-enhanced shunt series method is a highly specific examination with a negative predictive value exceeding that of head computed tomography and plain shunt series. Compared to radionuclide marker studies, contrast-enhanced shunt series demonstrate better spatiotemporal resolution, enabling focused local surgical repair.

Walking assessment after lumbar puncture in normal-pressure hydrocephalus: a delayed improvement over 3 days

J Neurosur (126) 148-157, 2017

The determination of gait improvement after lumbar puncture (LP) in idiopathic normal-pressure hydrocephalus (iNPH) is crucial, but the best time for such an assessment is unclear. The authors determined the time course of improvement in walking after LP for single-task and dual-task walking in iNPH.

METHODS: In patients with iNPH, sequential recordings of gait velocity were obtained prior to LP (time point [TP]0), 1–8 hours after LP (TP1), 24 hours after LP (TP2), 48 hours after LP (TP3), and 72 hours after LP (TP4). Gait analysis was performed using a pressure-sensitive carpet (GAITRite) under 4 conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), walking while performing serial 7 subtractions (dual-task walking with serial 7 [DTS7]), and walking while performing verbal fluency tasks (dual-task walking with verbal fluency [DTVF]).

RESULTS: Twenty-four patients with a mean age of 76.1 ± 7.8 years were included in this study. Objective responder status moderately coincided with the self-estimation of the patients with subjective high false-positive results (83%). The extent of improvement was greater for single-task walking than for dual-task walking (p < 0.05). Significant increases in walking speed were found at TP2 for STPS (p = 0.042) and DTVF (p = 0.046) and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). Enlargement of the ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP3 correlated with the shunt response in 18 patients.

CONCLUSIONS: Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24–48 hours after the LP. This time point is also best to predict the response to shunting. For dual-task paradigms, maximal improvement appears to occur later (48 to 72 hours). Assessment of gait should be performed at Day 2 or 3 after LP.

Surgical treatment of long-standing overt ventriculomegaly in adults (LOVA)

Acta Neurochir (2017) 159:71–79

Longstanding overt ventriculomegaly in adults (LOVA) is characterised by chronic hydrocephalus presumed to begin during infancy, but arresting before becoming clinically detectable. Later in life clinical features of hydrocephalus ensue, typically in the 5th or 6th decades. Only a relatively small number of LOVA case series have been published, and ambiguity remains regarding optimal management. This case series describes a series of patients with LOVA treated successfully at a single neurosurgical institution using endoscopic third ventriculostomy (ETV).

Methods: A series of 14 patients were diagnosed with LOVA using established clinical and radiological criteria. All patients underwent an ETV and their clinical conditions were followed up for up to 5 years post-operatively.

Results: Fourteen patients (100 %) reported either improvement or halt of progression in their presenting symptoms 3 months after ETV; 93 % of patients (n = 13) did not require any further surgical intervention. One patient (7 %) reported deterioration in symptoms beyond 3 months post-operatively, which necessitated further surgery (ventriculoperitoneal shunt). These promising outcomes after ETV are mirrored in numerous other LOVA case series. Other works have analysed the value of CSF shunting procedures in LOVA, with mixed results. A direct, prospective comparison of outcomes after shunt procedures and ETV, with a specific focus on LOVA patients, is yet to be completed. A minority of patients fail to respond, or develop recurrence of symptoms, months or years after initial surgical intervention.

Conclusions: ETV is an attractive option for surgical treatment of LOVA. After surgical treatment for LOVA, long-term follow-up should be considered to screen for late recurrence of the condition.

Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus

Acta Neurochir (2017) 159: 51-61

It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH).


In this study, we retrospectively analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy.


The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer’s disease (AD)-related proteins (amyloid-β, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (P = 0.014). High mean ICP was associated with Evans’ index (EI; P = 0.025), disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were associated with less atrophy of the medial temporal lobe (P = 0.018) and more severe disproportionality between the sylvian and suprasylvian subarachnoid spaces (P = 0.001).


The EI and disproportional sylvian and suprasylvian subarachnoid spaces were associated with mean ICP. Disproportionality was also associated with ICP B waves. These associations, although rather weak, with elevated ICP in 24-h measurements, support their value in iNPH diagnostics and suggest that these radiological markers are potentially related to the pathogenesis of iNPH. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation.

Natural history of colloid cysts of the third ventricle

J Neurosurg 125:1420–1430, 2016

Colloid cysts are rare, histologically benign lesions that may result in obstructive hydrocephalus and death. Understanding the natural history of colloid cysts has been challenging given their low incidence and the small number of cases in most reported series. This has complicated efforts to establish reliable prognostic factors and surgical indications, particularly for asymptomatic patients with incidental lesions. Risk factors for obstructive hydrocephalus in the setting of colloid cysts remain poorly defined, and there are no grading scales on which to develop standard management strategies.

Methods The authors performed a single-center retrospective review of all cases of colloid cysts of the third ventricle treated over nearly 2 decades at Washington University. Univariate analysis was used to identify clinical, imaging, and anatomical factors associated with 2 outcome variables: symptomatic clinical status and presentation with obstructive hydrocephalus. A risk-prediction model was defined using bootstrapped logistic regression. Predictive factors were then combined into a simple 5-point clinical scale referred to as the Colloid Cyst Risk Score (CCRS), and this was evaluated with receiver-operator characteristics.

Results The study included 163 colloid cysts, more than half of which were discovered incidentally. More than half of the incidental cysts (58%) were followed with surveillance neuroimaging (mean follow-up 5.1 years). Five patients with incidental cysts (8.8%) progressed and underwent resection. No patient with an incidental, asymptomatic colloid cyst experienced acute obstructive hydrocephalus or sudden neurological deterioration in the absence of antecedent trauma. Nearly half (46.2%) of symptomatic patients presented with hydrocephalus. Eight patients (12.3%) presented acutely, and there were 2 deaths due to obstructive hydrocephalus and herniation. The authors identified several factors that were strongly correlated with the 2 outcome variables and defined third ventricle risk zones where colloid cysts can cause obstructive hydrocephalus. No patient with a lesion outside these risk zones presented with obstructive hydrocephalus. The CCRS had significant predictive capacity for symptomatic clinical status (area under the curve [AUC] 0.917) and obstructive hydrocephalus (AUC 0.845). A CCRS ≥ 4 was significantly associated with obstructive hydrocephalus (p < 0.0001, RR 19.4).

Conclusions Patients with incidentally discovered colloid cysts can experience both lesion enlargement and symptom progression or less commonly, contraction and symptom regression. Incidental lesions rarely cause acute obstructive hydrocephalus or sudden neurological deterioration in the absence of antecedent trauma. Nearly one-half of patients with symptomatic colloid cysts present with obstructive hydrocephalus, which has an associated 3.1% risk of death. The CCRS is a simple 5-point clinical tool that can be used to identify symptomatic lesions and stratify the risk of obstructive hydrocephalus. External validation of the CCRS will be necessary before objective surgical indications can be established. Surgical intervention should be considered for all patients with CCRS ≥ 4, as they represent the high-risk subgroup.

Does aqueductal stenosis influence the lumbar infusion test in normal-pressure hydrocephalus?

Acta Neurochir (2016) 158:2305–2310

Late-onset idiopathic aqueductal stenosis may present with clinical features indistinct from idiopathic normal-pressure hydrocephalus (NPH). Moreover, aqueductal stenosis (AS) is not always detected by conventional magnetic resonance imaging (MRI). The aim of this study was to compare the hydrodynamic pattern among NPH patients according to the patency of the aqueduct.

Methods Fifty-six consecutive lumbar infusion tests were performed in patients with NPH syndrome. Precipitating causes of hydrocephalus were excluded, and aqueductal patency was examined through high-resolution, T2-weighted 3D MRI. Patients were classified into two groups: non-patent aqueduct and patent aqueduct. Mean values of pressure and pulse amplitude were obtained from basal and plateau stages of infusion studies.

Results Twelve of 56 patients with NPH-like symptoms presented with morphological AS (21.4 %). Patent aqueduct and non-patent aqueduct groups had similar values of mean opening lumbar pressure (8.2 vs. 8.1 mmHg), and mean opening pulse amplitude (3.1 vs. 2.9 mmHg). Mean pressure in the plateau stage (28.6 vs. 23.2 mmHg), and mean pulse amplitude in the plateau stage (12.5 vs. 10.6 mmHg) were higher in the patent aqueduct group. These differences were not statistically significant. Only Rout was significantly higher in the patent aqueduct group (13.6 vs. 10.1 mmHg/ml/min). One-third of NPH patients with AS presented Rout >12 mmHg/ ml/min.

Conclusions No differences in mean pressure or pulse amplitude during basal and plateau epochs of the lumbar infusion test in NPH patients were detected, regardless of aqueductal patency. However, Rout was significantly higher in patients with patent aqueduct.

One-year outcome in patients with idiopathic normal-pressure hydrocephalus: comparison of lumboperitoneal shunt to ventriculoperitoneal shunt

J Neurosurg 125:1483–1492, 2016

Idiopathic normal pressure hydrocephalus (iNPH) is treated with cerebrospinal fluid shunting, and implantation of a ventriculoperitoneal shunt (VPS) is the current standard treatment. The objective of this study was to compare the efficacy and safety of VPSs and lumboperitoneal shunts (LPSs) for patients with iNPH.

Methods The authors conducted a prospective multicenter study of LPS use for patients with iNPH. Eighty-three patients with iNPH (age 60 to 85 years) who presented with ventriculomegaly and high-convexity and medial subarachnoid space tightness on MR images were recruited from 20 neurological or neurosurgical centers in Japan between March 1, 2010, and October 19, 2011. The primary outcome was the modified Rankin Scale (mRS) score 1 year after surgery, and the secondary outcome included scores on the iNPH grading scale (iNPHGS). A previously conducted VPS cohort study with the same inclusion criteria and primary and secondary end points was used as a historical control.

Results: The proportion of patients who achieved a favorable outcome (i.e., improvement of at least 1 point in their mRS score) was 63% (95% CI 51%–73%) and was comparable to values reported with VPS implantation (69%, 95% CI 59%–78%). Using the iNPHGS, the 1-year improvement rate was 75% (95% CI 64%–84%) and was comparable to the rate found in the VPS study (77%, 95% CI 68%–84%). The proportion of patients experiencing serious adverse events (SAEs) and non-SAEs did not differ signi cantly between the groups at 1 year after surgery (SAEs: 19 [22%] of 87 LPS patients vs 15 [15%] of 100 VPS patients, p = 0.226; non-SAEs: 24 [27.6%] LPS patients vs 20 [20%] VPS patients, p = 0.223). However, shunt revisions were more common in LPS-treated patients than in VPS-treated patients (6 [7%] vs 1 [1%]).

Conclusions The efficacy and safety rates for LPSs with programmable valves are comparable to those for VPSs for the treatment of patients with iNPH. Despite the relatively high shunt failure rate, an LPS can be the treatment of choice because of its minimal invasiveness and avoidance of brain injury.


Hydrocephalus: an underrated long-term complication of microvascular decompression for trigeminal neuralgia

External lumbar drain- A pragmatic test for prediction of shunt outcomes in idiopathic normal pressure hydrocephalus

Acta Neurochir (2016) 158:2203–2206

Hydrocephalus is a common complication of posterior fossa surgery, but its real incidence after microvascular decompression (MVD) for idiopathic trigeminal neuralgia (TN) still remains unclear. The aim of this study was to focus on the potential association between MVD and hydrocephalus as a surgery-related complication.

Methods All patients who underwent MVD procedure for idiopathic TN at our institute between 2009 and 2014 were reviewed to search for early or late postoperative hydrocephalus.

Results There were 259 consecutive patients affected by idiopathic TN who underwent MVD procedure at our institution between 2009 and 2014 (113 men, 146 women; mean age 59 years, range 30–87 years; mean follow-up 40.92 months, range 8–48 months). Nine patients (3.47 %) developed communicating hydrocephalus after hospital discharge and underwent standard ventriculo-peritoneal shunt. No cases of acute hydrocephalus were noticed.

Conclusions Our study suggests that late communicating hydrocephalus may be an underrated potential long-term complication of MVD surgery.


Comparison of elevated intracranial pressure pulse amplitude and disproportionately enlarged subarachnoid space (DESH) for prediction of surgical results in suspected idiopathic normal pressure hydrocephalus

External lumbar drain- A pragmatic test for prediction of shunt outcomes in idiopathic normal pressure hydrocephalus

Acta Neurochir (2016) 158:2207–2213

To compare the prognostic value of pulse amplitude on intracranial pressure (ICP) monitoring and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on magnetic resonance imaging (MRI) for predicting surgical benefit after shunt placement in idiopathic normal pressure hydrocephalus (iNPH).

Method Patients with suspected iNPH were prospectively recruited from a single centre. All patients received preoperative MRI and ICP monitoring. Patients were classified as shunt responders if they had an improvement of one point or more on the NPH score at 1 year post-surgery. The sensitivity, specificity, Youden index, and positive and negative predictive values of the two diagnostic methods were calculated.

Results Sixty-four of 89 patients clinically improved at 1 year post-surgery and were classed as shunt responders. Positive DESH findings had a sensitivity of 79.4 % and specificity of 80.8 % for predicting shunt responders. Fifty-five of 89 patients had positive DESH findings: 50 of these responded to VP shunt, giving a positive and negative predictive value of 90.9 % and 61.8 %, respectively. Fifty-seven of 89 patients had high ICP pulse amplitude. High ICP pulse amplitude had a sensitivity of 84.4 %, specificity of 88 %, positive predictive value of 94.7 % and negative predictive value of 61.8 % for predicting shunt responders.

Conclusions Both positive DESH findings and high ICP pulse amplitude support the diagnosis of iNPH and provide additional diagnostic value for predicting shunt-responsive patients; however, high ICP amplitude was more accurate than positive DESH findings, although it is an invasive test.

Endoscopic third ventriculostomy for treatment of adult hydrocephalus: long-term follow-up of 163 patients


Neurosurg Focus 41 (3):E3, 2016

The authors performed a retrospective chart review of all adult patients (age ≥ 18 years) with symptomatic hydrocephalus treated with ETV in Calgary, Canada, over a span of 20 years (1994–2014). Patients were dichotomized into a primary or secondary ETV cohort based on whether ETV was the initial treatment modality for the hydrocephalus or if other CSF diversion procedures had been previously attempted respectively. Primary outcomes were subjective patient-reported clinical improvement within 12 weeks of surgery and the need for any CSF diversion procedures after the initial ETV during the span of the study. Categorical and actuarial data analysis was done to compare the outcomes of the primary versus secondary ETV cohorts.

Results A total of 163 adult patients with symptomatic hydrocephalus treated with ETV were identified and followed over an average of 98.6 months (range 0.1–230.4 months). All patients presented with signs of intracranial hypertension or other neurological symptoms. The primary ETV group consisted of 112 patients, and the secondary ETV consisted of 51 patients who presented with failed ventriculoperitoneal (VP) shunts. After the initial ETV procedure, clinical improvement was reported more frequently by patients in the primary cohort (87%) relative to those in the secondary ETV cohort (65%, p = 0.001). Additionally, patients in the primary ETV group required fewer reoperations (p < 0.001), with cumulative ETV survival time favoring this primary ETV cohort over the course of the follow-up period (p < 0.001). Fifteen patients required repeat ETV, with all but one experiencing successful relief of symptoms. Patients in the secondary ETV cohort also had a higher incidence of complications, with one occurring in 8 patients (16%) compared with 2 in the primary ETV group (2%; p = 0.010), although most complications were minor.

Conclusions ETV is an effective long-term treatment for selected adult patients with hydrocephalus. The overall ETV success rate when it was the primary treatment modality for adult hydrocephalus was approximately 87%, and 99% of patients experience symptomatic improvement after 2 ETVs. Patients in whom VP shunt surgery fails prior to an ETV have a 22% relative risk of ETV failure and an almost eightfold complication rate, although mostly minor, when compared with patients who undergo a primary ETV. Most ETV failures occur within the first 7 months of surgery in patients treated with primary ETV, but the time to failure is more prolonged in patients who present with failed previous shunts.

Hydrocephalus: cerebral aquaporin-4 and computational modeling

Aquaporin-4 channels

Neurosurg Focus 41 (3):E8, 2016

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting.

This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized.

Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.

Fractional anisotropy in patients with disproportionately enlarged subarachnoid space hydrocephalus

Fractional anisotropy in patients with disproportionately enlarged subarachnoid space hydrocephalus

Acta Neurochir (2016) 158:1495–1500

Disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings on MRI were described as a prognostic factor for responsiveness to the treatment of idiopathic normal pressure hydrocephalus (iNPH). Our premise is that DESH could be associated with compression of the cerebral white matter. Microstructural changes can be identified using diffusion tensor imaging (DTI), specifically fractional anisotropy (FA). The aim of this study is to compare FA in iNPH patients with and without DESH and healthy controls.

Methods: We analysed 1.5-T MRI scans of patients fulfilling the criteria of probable or possible iNPH and positive supplementary tests before and after surgery (ventriculo-peritoneal shunt). FA was measured in the anterior and posterior limb of the internal capsule (PLIC) and in the corpus callosum. Patients were divided into the DESH and non-DESH group. These data were also compared to FA values in the control group.

Results: Twenty-seven patients and 24 healthy controls were enrolled. DESH was present in 15 patients and lacking in 12. Twenty-three iNPH patients were shunt responders (85.2 %), and 4 were non-responders (14.8 %). All patients in the DESH group were shunt responders. In the non-DESH group, eight patients were responders (66.7 %). A significant difference between the DESH and non-DESH group was found in the FA of the PLIC. The mean value of FA in the PLIC was 0.72 in the DESH group and 0.66 in the non-DESH group. After the surgery FA decreased in both groups. In the DESH iNPH group FA PLIC decreased to 0.65 and in the non-DESH iNPH group to 0.60. In the healthy controls, the mean FA in the PLIC was 0.58.

Conclusion: DESH on MRI scans is related to a higher FA in the PLIC with a decrease after the surgery. It reflects a more severe compression of the white matter than in non-DESH patients or healthy volunteers. DESH patients had better outcome than non-DESH patients. This study confirmed the importance of DESH as a supportive sign for iNPH.

Defining a Standardized Approach for the Bedside Insertion of Temporal Horn External Ventricular Drains

Standardized Approach for the Bedside Insertion of Temporal Horn External Ventricular Drains

Neurosurgery 79:296–304, 2016

A trapped temporal horn can be emergently decompressed by inserting a bedside temporal horn external ventricular drain (tEVD). However, no standardized method for this procedure has been described.

OBJECTIVE: To identify methods for bedside tEVD insertion, and determine the safest, most accurate, and most easily standardized approach.

METHODS: Volumetric images of 20 patients with trapped temporal horns were analyzed. Three tEVD approaches (perpendicular, lateral, and medial) were defined, along with standardized insertion points and external landmarks for trajectory guidance. Predicted success in penetrating the temporal horn, skin-to-temporal horn entrance distance, temporal horn distance traversed, and trajectory target error and accuracy were evaluated; data were compared with independent sample t tests.

RESULTS: Nineteen of 20 cases were analyzed; 13 had critical temporal horn entrapment. Penetration was achieved in 100% of perpendicular and 84% (16/19) of lateral and medial approaches (92% [12/13] of critical entrapments). In 19 patients, trajectory error was not significantly different among approaches. The perpendicular approach had significantly more accuracy than the lateral (P = .01) and medial (P = .002) approaches. The lateral approach afforded significantly more traversable distance than the perpendicular approach (P = .009). In cases with critical entrapment, the perpendicular approach had significantly less error (P = .02) and significantly better accuracy (P = .02) than the medial approach. The perpendicular approach trended toward more accuracy than the lateral approach (P = .06).

CONCLUSION: The perpendicular approach appears to be the easiest, safest, and most reliable approach tested. We recommend conducting bedside tEVD placement only in patients with a critically dilated temporal horn who are clinically deteriorating at a rate that prohibits other procedures.

Fewer complications with bolt-connected than tunneled external ventricular drainage


Acta Neurochir (2016) 158:1491–1494

Ventriculostomy/external ventricular drain (EVD) is a common neurosurgical procedure. Various techniques are used to fixate the drain and the objective of this study was, in a retrospective setting, to compare the incidence of complications when using bolt-connected EVD (BC-EVD) versus tunneled EVD (T-EVD).

Methods All patients subjected to an EVD performed through a new burr hole from 2009 through 2010 at two Depts. of Neurosurgery in Denmark (Odense and Aarhus) were retrospectively identified. Patient files were evaluated for EVD fixation technique (tunneled or bolt-connected EVD) and complications including unintended removal, catheter obstruction, infection, CSF leakage, and mechanical problems.

Results A total of 271 patients with 272 separate EVDs met the inclusion criteria. There was a statistically higher rate of complications leading to reinsertion in the tunneled EVD group (40 %), compared to the bolt-connected EVD group (6.5 %). There was no significant difference in infection rates.

Conclusions Tunneled EVD has a relatively high frequency of complications leading to reinsertion. The use of Bolt-connected EVD technique can lower this frequency significantly. The number needed to treat is three for preventing a complication requiring reinsertion. Infection rates are low for both types of ventriculostomies. Accordingly, we recommend use of Bolt-connected EVDs in neurosurgical practice.

Hydrocephalus in vein of Galen malformation: etiologies and therapeutic management implications

Hydrocephalus in vein of Galen malformation

Acta Neurochir (2016) 158:1279–1284

Up to now, only little is known about hydrocephalus (HC) in vein of Galen malformation (VGM).We want to present the different etiologies and our long-term experience (1992–2015) in the management of HC.

Methods Out of 44 treated children with VGM, we retrospectively reviewed all cases with HC.We analyzed the etiologies, our treatment results and complications.

Results Twenty-one children (48 %) presented either with HC or developed it over time. In 21% of those cases, high venous pressure was presumably the sole cause. Until 2009, seven of them received ventriculoperitoneal (VP) shunting; six of those resulted in severe postoperative complications. The remaining children have been treated successfully by endovascular embolization. Five out of the 44 children (11 %) developed HC after intraventricular hemorrhage. In four cases, those children were treated with positive results by using transient external ventricular drainages. In one case a VP shunt with highest valve pressure was inserted. Another four children (9 %) presented with aqueductal stenosis-related HC caused by either dilated venous outflow or space-occupying coil masses after embolization. The latter case was successfully treated by ventriculocisternostomy, whereas endovascular treatment decreased the venous outflow in size and thus resolved the HC in the other cases. In the remaining cases (7 %), atrophy due to melting brain syndrome led to HC ex vacuo.

Conclusions HC in VGM is a common phenomenon with several etiologies requiring different treatments. In most cases, embolization of the VGM as sole treatment is completely sufficient in order to decrease high venous pressure. However, certain other causes of HC should be treated in an interdisciplinary setting by specialized neurosurgeons.

Female gender predisposes for cerebrospinal fluid overdrainage in ventriculoperitoneal shunting

Female gender predisposes for cerebrospinal fluid overdrainage in ventriculoperitoneal shunting

Acta Neurochir (2016) 158:1273–1278

Gravitational valves (GVs) prevent overdrainage in ventriculoperitoneal shunting (VPS). However, there are no data available on the appropriate opening pressure in the shunt system when implementing a GV. We performed a retrospective analysis of hydrocephalic patients who were successfully treated with VPS which included one or more GV.

Method In this retrospective study in adult VPS patients with GVs, we analysed all available data, including the most recent computed tomography (CT) scans, to determine the best adjustments for alleviating any symptoms of overdrainage and underdrainage. Vertical effective opening pressure (VEOP) of the entire shunt system, including the differential pressure valve, was determined.

Results One hundred and twenty-two patients were eligible for the study. Of these, female patients revealed a higher VEOP compared with males (mean, 35.6 cmH2O [SD ± 2.46] vs 28.9 cmH2O [SD±0.87], respectively, p=0.0072, t-test). In patients older than 60 years, lower VEOPs, by a mean of 6.76 cmH2O± 2.37 (p = 0.0051), were necessary. Mean VEOP was found to be high in idiopathic intracranial hypertension (IIH; 41.6 cmH2O) and malresorptive and congenital HC (35.9 and 36.3), but low in normal pressure HC (27.5, p =0.0229; one-way ANOVA). In the total cohort, body mass index (BMI) and height did not correlate with VEOP. Twelve patients required a VEOP of more than 40 cmH2O, and in eight of these patients this was accomplished by using multiple GVs. All but one of these eight patients were of female gender, and none of the latter were treated for normal pressure hydrocephalus (NPH) (p = 0.0044 and p = 0.0032, Fisher’s exact test).

Conclusions In adult VPS patients, female gender increases the risk of overdrainage requiring higher VEOPs. Initial implantation of adjustable GV should be considered in female patients treated with VP shunts for pathology other than NPH.

Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus


J Neurosurg 124:350–358, 2016

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient’s clinical symptoms.

Methods Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients’ clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)–based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis.

Results Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxelbased analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus.

Conclusions This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.

Neurosurgery Department. “La Fe” University Hospital. Valencia, Spain


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