Acute low-pressure hydrocephalus: a case series and systematic review of 195 patients

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  • 1 Department of Surgery, University of Alberta, Edmonton;
  • | 2 Department of Clinical Neurosciences, University of Calgary; and
  • | 3 Department of Radiology, University of Calgary, Alberta, Canada
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OBJECTIVE

Acute low-pressure hydrocephalus (ALPH) is characterized by clinical manifestations of an apparent raised intracranial pressure (ICP) and ventriculomegaly despite measured ICP that is below the expected range (i.e., typically ≤ 5 cm H2O). ALPH is often refractory to standard hydrocephalus intervention protocols and the ICP paradox commonly leads to delayed diagnosis. The aim of this study was to characterize ALPH and develop an algorithm to facilitate diagnosis and management for patients with ALPH.

METHODS

EMBASE, MEDLINE, and Google Scholar databases were searched for ALPH cases from its first description in 1994 until 2019. Cases that met inclusion criteria were pooled with cases managed at the authors’ institution. Patient characteristics, presenting signs/symptoms, precipitating factors, temporizing interventions, definitive treatment, and patient outcomes were recorded.

RESULTS

There were 195 patients identified, with 42 local and 153 from the literature review (53 pediatric patients and 142 adults). Decreased level of consciousness was the predominant clinical sign. The most common etiologies of hydrocephalus were neoplasm and hemorrhage. While the majority of ALPH occurred spontaneously, 39% of pediatric patients had previously undergone a lumbar puncture. Prior to ALPH diagnosis, 92% of pediatric and 39% of adult patients had a ventricular shunt in situ. The most common temporizing intervention was subatmospheric CSF drainage. The majority of patients underwent a shunt insertion/revision or endoscopic third ventriculostomy as definitive ALPH treatment. Although the mortality rate was 11%, 83% of pediatric and 49% of adult patients returned to their pre-ALPH neurological functional status after definitive treatment. Outcomes were related to both the severity of the underlying neurosurgical disease causing the hydrocephalus and the efficacy of ALPH treatment.

CONCLUSIONS

ALPH is an underrecognized variant phenotype of hydrocephalus that is associated with multiple etiologies and can be challenging to treat as it frequently does not initially respond to standard strategies of CSF shunting. With early recognition, ALPH can be effectively managed. A management algorithm is provided as a guide for this purpose.

ABBREVIATIONS

ALPH = acute low-pressure hydrocephalus; ETV = endoscopic third ventriculostomy; EVD = external ventricular drain; ICP = intracranial pressure; iNPH = idiopathic normal pressure hydrocephalus; SAS = subarachnoid space.

OBJECTIVE

Acute low-pressure hydrocephalus (ALPH) is characterized by clinical manifestations of an apparent raised intracranial pressure (ICP) and ventriculomegaly despite measured ICP that is below the expected range (i.e., typically ≤ 5 cm H2O). ALPH is often refractory to standard hydrocephalus intervention protocols and the ICP paradox commonly leads to delayed diagnosis. The aim of this study was to characterize ALPH and develop an algorithm to facilitate diagnosis and management for patients with ALPH.

METHODS

EMBASE, MEDLINE, and Google Scholar databases were searched for ALPH cases from its first description in 1994 until 2019. Cases that met inclusion criteria were pooled with cases managed at the authors’ institution. Patient characteristics, presenting signs/symptoms, precipitating factors, temporizing interventions, definitive treatment, and patient outcomes were recorded.

RESULTS

There were 195 patients identified, with 42 local and 153 from the literature review (53 pediatric patients and 142 adults). Decreased level of consciousness was the predominant clinical sign. The most common etiologies of hydrocephalus were neoplasm and hemorrhage. While the majority of ALPH occurred spontaneously, 39% of pediatric patients had previously undergone a lumbar puncture. Prior to ALPH diagnosis, 92% of pediatric and 39% of adult patients had a ventricular shunt in situ. The most common temporizing intervention was subatmospheric CSF drainage. The majority of patients underwent a shunt insertion/revision or endoscopic third ventriculostomy as definitive ALPH treatment. Although the mortality rate was 11%, 83% of pediatric and 49% of adult patients returned to their pre-ALPH neurological functional status after definitive treatment. Outcomes were related to both the severity of the underlying neurosurgical disease causing the hydrocephalus and the efficacy of ALPH treatment.

CONCLUSIONS

ALPH is an underrecognized variant phenotype of hydrocephalus that is associated with multiple etiologies and can be challenging to treat as it frequently does not initially respond to standard strategies of CSF shunting. With early recognition, ALPH can be effectively managed. A management algorithm is provided as a guide for this purpose.

ABBREVIATIONS

ALPH = acute low-pressure hydrocephalus; ETV = endoscopic third ventriculostomy; EVD = external ventricular drain; ICP = intracranial pressure; iNPH = idiopathic normal pressure hydrocephalus; SAS = subarachnoid space.

In Brief

Acute low-pressure hydrocephalus (ALPH) is a neurological condition that is very difficult to treat because despite patients having clinical manifestations of high pressure and large fluid spaces in the brain, their measured pressures are paradoxically low and not amenable to standard treatments. In this study the authors assessed 195 patients with ALPH and present diagnosis and treatment strategies in managing this debilitating neurological disorder. This study is the largest to date on this topic and the treatment algorithm provided should be a valuable resource for neurosurgeons faced with management of this challenging problem.

Hydrocephalus is a condition characterized by accumulation of CSF within the CNS that results from a loss of equilibrium between CSF production and absorption.1 While there are several forms of hydrocephalus in which an inciting event is not identifiable, others occur when an antecedent event such as hemorrhage, infection, or trauma leads to obstruction of CSF egress pathways, resulting in ventriculomegaly.2 Typically, acute hydrocephalus is associated with raised intracranial pressure (ICP) and patients present with symptoms such as headache, nausea and vomiting, cranial nerve palsies, visual disturbance, altered level of consciousness, and eventually coma and death if untreated.2,3 Exceptions occur with the chronic hydrocephalic conditions, including previously undiagnosed chronic hydrocephalus4,5 and idiopathic normal pressure hydrocephalus (iNPH),6,7 which occur in adults in whom the ICP is typically within the normal range.7,8

Acute low-pressure hydrocephalus (ALPH) is a variant phenotype of hydrocephalus in which patients present with symptoms of apparent raised ICP with ventriculomegaly despite a measured ICP that is less than expected (typically ≤ 5 cm H2O, or even subatmospheric).9–11 The paradox is that ICP is inappropriately low for the degree of ventriculomegaly and clinical symptoms.9–11 Due to its enigmatic characteristics, ALPH is frequently unrecognized, and patients tend to undergo multiple unsuccessful shunt or external ventricular drain (EVD) revisions for presumed indications of device failure before the diagnosis of ALPH is made.12 Temporizing EVDs fail to drain CSF at standard drainage height settings and shunts are ineffective at diverting CSF from abnormally low-pressure dilated ventricles into distal sites.

In the literature, the ALPH phenomenon has been given several names, including low-pressure hydrocephalus,10 negative-pressure hydrocephalus,11 and syndrome of inappropriately low-pressure hydrocephalus.9 There is a definite need for more information regarding factors that make patients susceptible to ALPH and how to facilitate early diagnosis. In addition, while different management strategies have been reported,9–11 there are no comprehensive protocols to guide the diagnosis and treatment of patients with ALPH.

This study presents a systematic review of 195 ALPH patients, which includes 42 patients who were managed at our center and 153 patients obtained through a systematic review of the published literature. This study was undertaken to determine ALPH patient characteristics, etiologic and precipitating factors, and to examine common treatment approaches and outcomes of patients affected by ALPH, with the goal of providing a treatment algorithm to facilitate identification and management of patients with ALPH.

Methods

Protocol and Registration

The study was registered with the international prospective register of systematic reviews (PROSPERO no. CRD42019132586). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.13 Ethics oversight was provided by the University of Calgary Research Ethics Board for the patients included from our center.

Eligibility and Inclusion and Exclusion Criteria

ALPH was defined as having: 1) clinical symptoms consistent with acute hydrocephalus; 2) head CT or MRI confirmation of ventriculomegaly determined by an Evan’s ratio ≥ 0.3;14 and 3) measured ICP that was ≤ 5 cm H2O and/or failure of external CSF drainage at standard height settings. Patients who had a subacute or chronic clinical picture consistent with previously undiagnosed chronic hydrocephalus4,5 or iNPH (cognitive decline, gait/equilibrium dysfunction, and urinary urgency, frequency, or incontinence)6,7 were excluded.

Information Sources, Literature Search, and Study Selection

Patients treated for ALPH between 1997 and 2019 at the Foothills Medical Center and Alberta Children’s Hospital—two tertiary care hospitals in Alberta, Canada, that care for a population of more than 2 million people—were identified from a local hydrocephalus database. Data on these patients were retrieved from their hospital and outpatient clinic charts and imaging records. Additional independent ALPH patient data were retrieved from published papers obtained through a systematic review of all English- or French-language papers published between 1994 (the year of the condition’s first description10) and April 2019. Additional papers were identified from the reference lists of the included papers.

Data Collection Process

A direct search of MEDLINE, EMBASE, and Google Scholar was performed in consultation with a librarian. For both the MEDLINE and EMBASE databases, we searched using the phrase “(hydrocephal* and (negative-pressure or low-pressure)).tw,kw”. In Google Scholar, we combined results from searching the exact phrase “negative-pressure hydrocephalus” and “low-pressure hydrocephalus” independently, utilizing the advanced search feature without any limitations on the scope of the search. Following deduplication of titles, two independent reviewers (M.B.K. and A.M.I.) reviewed the abstracts, then performed a full-text review and data extraction of relevant studies. Discrepancies at any stage of the review and data extraction were resolved by consensus among reviewers, with guidance of the senior investigator (M.G.H.).

Data Items

Extracted data on patient demographics included age (in years) and sex. The most likely etiology of hydrocephalus was reported in the categories of hemorrhage, neoplasm, trauma, congenital, infection, or unknown. ALPH-associated symptoms were categorized into depressed level of consciousness, headache, nausea/vomiting, cranial nerve paresis, or gait disturbance. To be conservative in our reporting of incidences, if a sign/symptom was not specifically reported as being present (i.e., missing data) it was counted as an absent finding. Potential precipitating factors of ALPH were categorized as unknown (no recent identifiable CSF drainage procedure), post–lumbar puncture, or postoperative with or without an identified CSF leak. The presence of a shunt prior to ALPH diagnosis and the duration (in months) between the shunt insertion/revision and ALPH diagnosis were recorded. Temporizing interventions of ALPH were categorized into conservative (no active treatment), subatmospheric CSF drainage, and neck wrapping. Definitive treatments were reported as endoscopic third ventriculostomy (ETV), shunt insertion/revision, or both. Each patient’s functional outcome relative to their pre-ALPH status was scored on a 5-point Likert scale, with a lower score representing a better outcome: 1 = return to baseline, 2 = mild disability, 3 = moderate disability, 4 = severe disability, and 5 = death. If an established outcome scale such as the Glasgow Outcome Scale17 or modified Rankin Scale31 were reported, they were translated into the same 5-point scale to ensure the data were uniform for comparisons. Using data source as the dependent variable, differences between patient characteristics and outcomes were assessed and no significant differences were identified.

Statistical Analyses, Summary Measures, and Synthesis of Results

All statistical analyses were performed using R (version 3.5.0, The R Foundation). Descriptive statistics of patient demographics, clinical factors, interventions, and outcomes were reported as percentages of the total number of patients with records available. Pediatric (age ≤ 18 years old) and adult (age > 18 years old) patients were reported separately. All studies were level 4 evidence or case reports, which resulted in significant heterogeneity of the data elements. A formal meta-analysis was not undertaken.

Results

Study Selection and Characteristics

The literature search recovered 537 records, 185 from MEDLINE, 246 from EMBASE, and 106 from Google Scholar, as well as 5 from reference review (Fig. 1). Following deduplication and review of abstracts, 41 papers underwent full review, 3 of which were excluded for failure to meet inclusion criteria. One hundred fifty-seven independent patients were identified from 38 papers. Four patients from 2 of the included studies11,15 were removed from the systematic review because they did not meet the inclusion criteria and, in one instance, was a repeated case from another report by the same group. Overall, 195 patients were included in the systematic review, which included 3 previously published cases9 and 39 unpublished cases from our institution (Supplementary Table 1).

FIG. 1.
FIG. 1.

Flowchart of a systematic review of the existing literature (1994–2019) on patients with ALPH.

Patient Characteristics

Of the 195 patients (110 male and 85 female), 53 were pediatric and 142 were adults with a median age of 7 (IQR 8.5) and 50 (IQR 25.0) years old, respectively. While the predominant etiology of hydrocephalus among all patients was hemorrhage, neoplasm was the most common in the pediatric group (74%), whereas hemorrhage (46%) and trauma (23%) accounted for the majority of the cases in adults. ALPH was identified in 16% and 36% of the pediatric and adult patients, respectively, after a CSF-related surgery (e.g., craniotomy), either to treat the hydrocephalus or the antecedent event. ALPH that was diagnosed after the patient had undergone a lumbar puncture was more common in the pediatric (31%) than in the adult (4%) patients. However, ALPH occurred without any preceding CSF-related procedure in more than 50% of all patients. While the recorded signs/symptoms were variable, the most common in both pediatric and adult patients was decreased level of consciousness (84% of children and 88% of adults), followed by headaches and cranial nerve deficits (Table 1).

TABLE 1.

Summary of patient demographics and clinical factors associated with ALPH

VariablePediatric PatientsAdults
No. of patients53142
Sex
 Female2560
 Male2882
Median age in yrs (IQR)7.0 (8.5)50.0 (25.0)
Etiology of hydrocephalus, n (%)
 Hemorrhage6 (11.3)65 (45.8)
 Neoplasm39 (73.6)22 (15.5)
 Trauma1 (1.9)32 (22.5)
 Congenital7 (13.2)12 (8.5)
 Infectious0 (0.0)7 (4.9)
 Unknown0 (0.0)4 (2.8)
CSF-related precipitating factor, n (%)*
 Postop craniotomy w/o CSF leak8 (16.3)31 (36.0)
 Post–lumbar puncture15 (30.6)3 (3.5)
 Unknown26 (53.1)47 (54.7)
 Postop w/ CSF leak0 (0.0)5 (5.8)
Symptoms, n (%)
 Decreased level of consciousness21 (84.0)78 (87.6)
 Headache12 (48.0)20 (22.5)
 Nausea/vomiting3 (12.0)9 (10.1)
 Cranial nerve deficit11 (44.0)10 (11.2)
 Gait disturbance4 (16.0)9 (10.1)

Patients with missing data were not included in the analysis. Percentages in each category are reported as number of cases of total number of patients with records.

Data available for 49 pediatric patients and 86 adults.

Data available for 25 pediatric patients and 89 adults.

Temporizing Interventions and Definitive Treatment

The diagnosis, acute intervention, and monitoring of ALPH requires an external CSF diversion strategy (Table 2). In this study, patients with a prior shunt in situ (92% pediatric patients and 39% adults) had undergone shunt externalization. Prior to the ALPH diagnosis, shunts had been in place for a median of 6.0 (IQR 10.0) and 1.5 (IQR 11.0) months among the pediatric and adult patients, respectively. However, it was frequently not possible to reliably determine whether shunts had been inserted prior to or during the hospital admission during which ALPH was diagnosed. Placement of an EVD occurred in 13% and 35% of pediatric and adult patients, respectively.

TABLE 2.

Treatment and outcomes for 195 patients with ALPH

VariablePediatricAdult
Total population53142
Previous shunt prior to ALPH diagnosis
 No. of records available5194
 Patients w/ shunt in situ, n (%)47 (92.2)37 (39.4)
 Median time from shunt placement to ALPH (IQR), mos6.0 (10.0)1.5 (11.0)
EVD
 No. of records available53103
 EVD inserted, n (%)7 (13.2)36 (35.0)
Temporizing intervention
 No. of records available3366
 Conservative approach, n (%)11 (33.3)1 (1.5)
 Subatmospheric CSF drainage, n (%)16 (48.5)53 (80.3)
 Neck wrapping, n (%)1 (3.0)4 (6.1)
 Subatmospheric CSF drainage plus neck wrapping, n (%)1 (3.0)6 (9.1)
 Other, n (%)*4 (12.1)2 (3.0)
Definitive treatment
 No. of records available4992
 ETV only, n (%)1 (2.0)10 (10.9)
 Shunt insertion/revision only, n (%)34 (69.4)62 (67.4)
 ETV plus shunt, n (%)4 (8.2)19 (20.7)
 Unknown, n (%)10 (20.4)1 (1.1)
Outcomes
 No. of records available53134
 Return to baseline, n (%)44 (83.0)65 (48.5)
 Mild residual symptoms, n (%)0 (0.0)12 (9.0)
 Moderate residual symptoms, n (%)0 (0.0)28 (20.9)
 Severe residual symptoms, n (%)3 (5.7)14 (10.4)
 Died, n (%)6 (11.3)15 (11.2)

Patients with missing data were not included in the analysis. Percentages in each category are reported as number of cases as a factor of the number of patient records available.

Other included blood patches for CSF leaks, lumbar drain, and septostomy.

With a CSF drainage device in place (externalized shunt or EVD), 67% of pediatric and 99% of adult patients required adjunctive strategies to facilitate CSF drainage, while the rest were managed without a clearly defined strategy. The most commonly used approach was subatmospheric CSF drainage with or without neck wrapping, which was performed in 52% and 89% of pediatric and adult patients, respectively. Shunt insertion/revision was the definitive treatment of choice in 69% and 67% of pediatric patients and adults, respectively, which in the case series from our center were often performed with a valveless reservoir or programmable valve set initially to the lowest pressure settings available. An ETV was performed in 10% and 32% of pediatric and adult patients, respectively, with or without a shunt. While 20% of pediatric patients recovered from ALPH without need for permanent CSF diversion surgery (shunt and/or ETV), only 1% of adults recovered as such.

Outcomes

The mortality rate was 11% in both pediatric and adult patients (Table 2). Except for 5 patients, all deaths occurred during the same admission when ALPH was diagnosed. However, whether the cause of death was related or unrelated to ALPH could not always be determined from the literature. Of all patients, 83% of children and 58% of adults returned to a level of function similar to before the onset of ALPH or had mild residual symptoms, whereas 6% of pediatric and 31% of adults had moderate to severe residual symptoms (Table 2).

Discussion

A fundamental challenge of ALPH is that in the context of acute hydrocephalus and a clinical phenotype reminiscent of high ICP, the observation of very low (in some cases subatmospheric) ICP readings is often perceived as counterintuitive to the traditional perspectives of the Monro-Kellie doctrine.16 Consequently, ALPH is challenging to diagnose and manage as it rarely initially responds to standard hydrocephalus treatment protocols. There are no current guidelines on the management of ALPH and there is limited information summarizing the common patient characteristics, treatment approaches, and patient outcomes to facilitate early recognition and timely successful treatment of the condition. In this study, the clinical data on 42 patients treated at our tertiary care center were combined with 153 patients obtained from a systematic review of 38 published case reports/series for a descriptive analysis, to characterize and develop an algorithm to enable early diagnosis and describe a management strategy for patients with ALPH.

Summary of Findings

The major findings of this study were as follows: 1) the most common presentation of ALPH in both the pediatric and adult populations was clinically significant depressed level of consciousness; 2) the three most common etiologies for ALPH were hemorrhage, neoplasm, and trauma; 3) approximately 30% of ALPH events occurred after cranial or initial shunt surgery, and a third of the pediatric patients had undergone a lumbar puncture prior to ALPH diagnosis; 4) the most common management interventions for ALPH were externalization of a preexisting shunt and/or insertion of an EVD to facilitate subatmospheric CSF drainage with or without neck wrapping; 5) mortality in this patient cohort was 11%, but the direct/indirect role ALPH in mortality was unclear and could not be quantified; 6) among surviving patients, over 80% of pediatric patients and almost half of adult ALPH patients returned to their pre-ALPH neurological functional status; and 7) over 20% of pediatric and only 1% of adult patients recovered without requiring permanent CSF diversion (shunt or ETV).

Pathophysiological Basis for Current ALPH Treatment Strategies

Several mechanisms have been proposed to explain the ICP paradox in ALPH.10,17,18 An early report on patients who presented with a shunt in situ suggested ALPH was an iatrogenic consequence of CSF drainage.10,19 While this assumption may account in part for the approximately 46% of patients in this study who were diagnosed with ALPH postoperatively or after undergoing a lumbar puncture, it does not account for the majority of cases that occurred without a known prior CSF-related procedure, which underscores the likely multifactorial pathophysiology of ALPH.

Rekate et al. suggested that ALPH occurs when an antecedent event such as hemorrhage, neoplasm, or trauma causes an isolation of the ventricular system from the cortical subarachnoid space (SAS),18 presumably as a result of a mechanical obstruction or as a result of SAS inflammation. The ventricular-SAS disconnection then leads to entrapment of CSF in the cortical SAS, which when drained (such as with a lumbar puncture or CSF leak), leads to a pressure differential that propagates ventriculomegaly without a rise in ICP.18 Our results lend support to Rekate et al.’s proposed mechanism on two fronts. For one, among the 42 patients treated at our center, there were approximately 10% of patients with identifiable aqueductal occlusion or fourth ventricular outlet obstruction who demonstrated a positive response to ETV, which lends support to the concept of cortical SAS isolation. Second, the ventricular-SAS disconnection theory would also help explain the 30% and 9% of pediatric and adult ALPH cases that were diagnosed after a lumbar puncture or postoperatively with a CSF leak. However, while directly relevant to many of the reported patients, Rekate et al.’s theory still does not explain the majority of the reviewed cases in which ALPH occurred without a history of a preceding CSF-related procedure. It is possible that challenges associated with identification of CSF leaks may be a contributory factor.20

An additional suggested mechanism that may facilitate ALPH development involves decreased elasticity or increased compliance in an abnormal brain, which allows for the development of progressive ventriculomegaly with low ICP.10 Utilizing MR elastography, Olivero et al. found that the brain stiffness of a 19-year-old patient, 3 weeks after ALPH resolution, was much lower than that of an aged-matched healthy control and another patient with an implanted shunt.17 It is possible that the concept of brain turgor/compliance partially explains why neck wrapping, with the goal of increasing brain stiffness, has shown some success as an adjunctive intervention in the management of ALPH, especially in patients who are refractory to subatmospheric CSF drainage alone.9,18,21,22 However, Hatt et al. did not identify any significant increases in mean brain stiffness on MR elastography in 9 healthy volunteers who underwent neck wrapping.23 It is feasible that the brain compliance changes in patients who develop ALPH are required before neck wrapping can produce measurable improvements in brain stiffness, or that the perceived effectiveness of neck wrapping is unrelated to brain compliance/elasticity issues.

Proposed Algorithm for the Management of ALPH

In spite of the varying proposed pathophysiological mechanisms of ALPH, the unified goal for its treatment is to reverse obstructive causes for hydrocephalus, drain the accumulating CSF, and establish CSF drainage pathways.9,18,24 In this review, subatmospheric CSF drainage and neck wrapping, followed by surgical establishment of the communication between the ventricles and the cortical SAS with an ETV with or without treatment of the hydrocephalus with a shunt, were the most common approaches utilized. Other approaches described less frequently included intermittent shunt valve pressing,25 septum pellucidotomy,26 and fenestration of loculated CSF,27 each with a limited role for effectiveness in the typical ALPH patient.

When severe acute hydrocephalus is diagnosed, the initial measured ICP may be high upon insertion/revision of an EVD or shunt. Thus, ALPH may not be suspected or diagnosed until the patient shows signs of clinical deterioration and/or increased ventricular size despite a patent EVD or shunt. The findings of this review demonstrate that treatment is possible and when effective, patient outcomes are often determined more by the underlying cause of the hydrocephalus and effects of the associated brain injury (e.g., subarachnoid hemorrhage or tumor). Although we were unable to assess differences in the efficacy between the different temporizing interventions and/or treatments, we have assimilated our experiences and the management approaches presented by the various authors included in the analysis to propose an algorithm for the management of ALPH. We anticipate that this algorithm will not only help guide the diagnosis, acute interventions, and long-term treatment of ALPH, but will also provide a standard platform for further research in the long-term outcomes of ALPH. Our proposed approach can be summarized into the following three main steps (Table 3, Fig. 2).

TABLE 3.

Summary of ALPH management algorithm

A. Establish the diagnosis
B. Stabilize the patient
 1) Remove a large volume of CSF (30–50 ml), and continuously drain 10–15 ml of CSF per hour; the baseline of effective CSF removal is established when clinical improvement and ventricular size reduction are present
C. Undertake definitive treatment
 1) Optimize ventricular size and monitor clinical improvement by systematic gradual increases in EVD height and steady CSF drainage; wean from the EVD if possible
 2) Consider ETV if the patient is clinically better with stable ventricular size but cannot be weaned from the EVD and ventricular anatomy is appropriate
 3) Consider permanent CSF diversion (shunt) if ICP remains ≥ 0 cm H2O, the patient is clinically better with stable ventricular size but cannot be weaned from the EVD or undergo a successful ETV
FIG. 2.
FIG. 2.

Proposed algorithm for the diagnosis and treatment of ALPH with a goal of definitive therapy. Three major steps in the algorithm are color-coded: pink (A) = establishment of the ALPH diagnosis; purple (B) = stabilization of the patient; and green (C) = undertaking definitive treatment with an ETV or shunt or both ETV and shunt. Red = permanent CSF diversion and resolution of ALPH.

Step 1: Establishment of the Diagnosis

The imperative first step to ALPH management is confirmation of the diagnosis. It is not uncommon to see a brief initial high opening pressure that subsequently drops to inappropriately low or subatmospheric values. We recommend ICP checks of at least 1-hour intervals following EVD insertion/shunt externalization to promptly recognize signs that are suspicious for the ALPH phenotype, which may include but are not limited to lack of clinical improvement, minimal CSF drainage despite unchanged or worsening ventriculomegaly, or drain meniscus reading less than +5 cm H2O when leveled at the foramen of Monro. Wu et al. recently proposed a classification scheme of hydrocephalus “based upon ventricular pressure” with high, normal, low, and negative pressure subtypes.24 However, the current evidence does not support that the subclassification of ALPH into low and negative pressure types is important enough to affect the proposed management strategy.

Step 2: Stabilization of the Patient

Once the ALPH phenotype has been confirmed, the next step should be to immediately effect a reduction in ventricular size to aim for improvement and then stabilization of the clinical status of the patient. This may be accomplished with one or more large volume aspirations of ventricular CSF (30–50 ml), followed by a set 10–15 ml removal of CSF per hour. Often this requires lowering the drain to very low levels to facilitate drainage that will meet the hourly target volume. Serial clinical reassessments and a repeat CT or MRI (e.g., fast-sequence MRI) head scan may be performed to ensure that the desired patient clinical and ventricular responses are appropriate.

Step 3: Undertaking Definitive Treatment

Once the patient has been stabilized and demonstrates signs of clinical improvement, usually associated with a reduction in the ventricle size, the patient should be considered for definitive treatment, which may be achieved with an ETV26,28,29 or ventricular shunt,9,11,30 or a combination of ETV and a shunt.

Optimization of Ventricular CSF Drainage. When the patient is clinically stable and the ventricular size has reduced in size, a CT or MRI (e.g., fast-sequence MRI) head scan is obtained to document baseline ventricular size.

The volume-based drain strategy should then be switched to an ICP-based drainage strategy, where drain resistance (height) is gradually raised to challenge brain compliance. Initially, the drain height should be set to achieve 10–15 ml/hr of unforced CSF drainage with maintenance of clinical status and ventricular size. In our experience, there has been significant variability in the initial EVD height setting and has ranged from −20 to −5 cm H2O. Once this has been established, the next steps involve raising the drain height (1–2 cm every 3–5 days) while ensuring steady CSF drainage (10–15 ml/hr) is maintained. We have identified that there can often be a significant time lag in the development of adverse patient responses to challenges to an increase in EVD height settings (clinical deterioration and increase in ventricular size). A significant percentage of patients demonstrate this delayed deterioration that can occur up to 3–5 days after even small increases in the drain height. The recommendation to undertake incremental changes every 3–5 days is provided to account for this common phenomenon. Ideally, the expectation is that these gradual challenges will help to progressively decrease brain compliance to a level that will facilitate weaning completely from the drain or bridge to a more definitive therapy.

The overall process may be very challenging in some patients with ALPH. In addition to subatmospheric CSF drainage, adjunctive measures such as neck wrapping or abdominal binders may be necessary in a small percentage of patients who are refractory to the temporization schedule (as was the case in 7.1% of patients in this analysis).

If Possible, Wean and Remove the EVD. Approximately 80% of pediatric patients and 99% of adults with ALPH remain drain-dependent and require permanent CSF diversion.

Consideration for Treatment With an ETV. At this point, it is advisable to determine if the patient is a candidate for an ETV, which if successful is usually associated with a normalization of CSF and ICP physiology. Even if the patient is not successfully weaned from the EVD after a successful ETV, the ALPH phenotype often resolves and the management of the hydrocephalus with a shunt can be accomplished with standard surgical protocols.

Patients who previously underwent shunt placement and those who present with anatomically appropriate obstructive hydrocephalus and noninflammatory variants of hydrocephalus related to congenital disorders, aqueductal stenosis, obstructive cysts, and tumors tend to be more suitable candidates for ETV, which can be considered early in the treatment algorithm. Patients with ALPH that is secondary to highly inflammatory conditions such as hemorrhage (e.g., subarachnoid hemorrhage), trauma, and infection are typically less likely to succeed with an ETV, as the perimesencephalic SAS undergoes scarring and fibrosis and consideration for ETV will typically be unwarranted.

If an ETV is performed, an attempt to more aggressively wean the EVD should be undertaken. While a dramatic decrease in ventricular size is not expected following an ETV, the patient should be monitored clinically and with appropriate serial neuroimaging to ensure the ventriculomegaly is not progressive. The timing and frequency of neuroimaging can usually be guided by the clinical state of the patient. If an ETV fails or is not a consideration, ventricular size and/or ICP should be further optimized with an externalized drain as described above.

Consideration for Treatment With a Shunt. Patients who are not candidates for an ETV or experience unsuccessful ETV or EVD weaning will require a shunt. There is no literature to indicate if a ventriculoperitoneal shunt is better than a ventriculoatrial shunt. Given the significance of lumbar puncture–related events associated with the onset of the ALPH phenotype, lumboperitoneal shunts are not recommended.

Local experience and what has been identified in the literature indicate that most patients will tolerate management of their ALPH with a shunt when they have been stable at EVD levels somewhere between −5 and 0 cm H2O. It is likely that the siphoning that can occur with a differential pressure valve actually aids in CSF drainage through the shunt system, especially in patients who are able to eventually sit and stand. It is recommended to use a programable or very low-pressure valve for the procedure. Programmable valves should typically be set at low settings, and from our experience antisiphon or flow restriction devices are not recommended. A programmable valve has the advantage to allow adjustment of shunt outflow resistance to manage any overdrainage issues that might be brought on by siphoning effects that can develop as the patient mobilizes.

Limitations

Although this paper provides the best estimates to date on the patterns of presentation, patient factors, diagnosis, and treatment of ALPH, which were collated from a large set of independent patient data, several limitations have to be addressed. First, all the included studies were level 4 or lower class of evidence, as they were uncontrolled cohort studies, case series, and case reports. Second, there was heterogeneity in the reported information from the case studies and series, including different patterns of reporting on patient symptoms, etiologies of hydrocephalus, treatment approaches, and outcome measures. This heterogeneity prohibited undertaking a reasonable meta-analysis. Third, the treatment recommendations are necessarily a combined result of what has been presented in the literature and local expert opinion. Finally, ALPH is not currently identified by a specific ICD code, and thus long-term follow-up data are difficult to determine at most neurosurgical centers without the use of local registries. Nevertheless, the 42 patients presented from our cohort have been followed prospectively in the Adult Hydrocephalus Clinic and there have been no major changes in their reported ALPH outcomes.

Conclusions

ALPH is an uncommon acute hydrocephalus phenotype that affects patients of all ages and from a wide range of initial insults. The exact incidence is unknown. We have presented diagnosis and treatment strategies that can assist neurosurgeons in managing the counterintuitive aspects of this disorder.

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: Hamilton, Keough, Isaacs. Acquisition of data: Hamilton, Keough, Isaacs, Urbaneja, Dronyk. Analysis and interpretation of data: Hamilton, Keough, Isaacs, Lapointe. Drafting the article: Hamilton, Keough, Isaacs. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Hamilton. Statistical analysis: Hamilton, Keough, Isaacs, Lapointe. Administrative/technical/material support: Hamilton, Urbaneja, Dronyk. Study supervision: Hamilton.

Supplemental Information

Online-Only Content

Supplemental material is available with the online version of the article.

References

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    Leinonen V , Vanninen R , Rauramaa T . Cerebrospinal fluid circulation and hydrocephalus . Handb Clin Neurol . 2017 ;145 :39 50 .

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    Cowan JA , McGirt MJ , Woodworth G , et al. The syndrome of hydrocephalus in young and middle-aged adults (SHYMA) . Neurol Res . 2005 ;27 (5 ):540 547 .

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    Ono K , Hatada J , Yamada M . Long-standing overt ventriculomegaly in adults (LOVA) needing ventriculo-peritoneal shunt with double programmable pressure valves. Article in Japanese . No Shinkei Geka . 2012 ;40 (1 ):37 42 .

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    Mori E , Ishikawa M , Kato T , et al. Guidelines for management of idiopathic normal pressure hydrocephalus: second edition . Neurol Med Chir (Tokyo) . 2012 ;52 (11 ):775 809 .

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    Relkin N , Marmarou A , Klinge P , et al. Diagnosing idiopathic normal-pressure hydrocephalus . Neurosurgery . 2005 ;57 (3 )(suppl):S4 S16 , ii–v .

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    Bräutigam K , Vakis A , Tsitsipanis C . Pathogenesis of idiopathic normal pressure hydrocephalus: a review of knowledge . J Clin Neurosci . 2019 ;61 :10 13 .

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    Hamilton MG , Price AV . Syndrome of inappropriately low-pressure acute hydrocephalus (SILPAH) . Acta Neurochir Suppl (Wien) . 2012 ;113 :155 159 .

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    Pang D , Altschuler E . Low-pressure hydrocephalic state and viscoelastic alterations in the brain . Neurosurgery . 1994 ;35 (4 ):643 656 .

    • Search Google Scholar
    • Export Citation
  • 11

    Vassilyadi M , Farmer JP , Montes JL . Negative-pressure hydrocephalus . J Neurosurg . 1995 ;83 (3 ):486 490 .

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    Filippidis AS , Kalani MY , Nakaji P , Rekate HL . Negative-pressure and low-pressure hydrocephalus: the role of cerebrospinal fluid leaks resulting from surgical approaches to the cranial base . J Neurosurg . 2011 ;115 (5 ):1031 1037 .

    • Search Google Scholar
    • Export Citation
  • 13

    Moher D , Liberati A , Tetzlaff J , Altman DG . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement . Int J Surg . 2010 ;8 (5 ):336 341 .

    • Search Google Scholar
    • Export Citation
  • 14

    O’Hayon BB , Drake JM , Ossip MG , et al. Frontal and occipital horn ratio: a linear estimate of ventricular size for multiple imaging modalities in pediatric hydrocephalus . Pediatr Neurosurg . 1998 ;29 (5 ):245 249 .

    • Search Google Scholar
    • Export Citation
  • 15

    Owler BK , Jacobson EE , Johnston IH . Low pressure hydrocephalus: issues of diagnosis and treatment in five cases . Br J Neurosurg . 2001 ;15 (4 ):353 359 .

    • Search Google Scholar
    • Export Citation
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    Weed LH . Some limitations of the Monro-Kellie hypothesis . Arch Surg . 1929 ;18 (4 ):1049 1068 .

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    Olivero WC , Wszalek T , Wang H , et al. Magnetic resonance elastography demonstrating low brain stiffness in a patient with low-pressure hydrocephalus: case report . Pediatr Neurosurg . 2016 ;51 (5 ):257 262 .

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    • Export Citation
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    Rekate HL , Nadkarni TD , Wallace D . The importance of the cortical subarachnoid space in understanding hydrocephalus . J Neurosurg Pediatr . 2008 ;2 (1 ):1 11 .

    • Search Google Scholar
    • Export Citation
  • 19

    Dias MS , Li V , Pollina J . Low-pressure shunt ‘malfunction’ following lumbar puncture in children with shunted obstructive hydrocephalus . Pediatr Neurosurg . 1999 ;30 (3 ):146 150 .

    • Search Google Scholar
    • Export Citation
  • 20

    Lin JP , Zhang SD , He FF , et al. The status of diagnosis and treatment to intracranial hypotension, including SIH . J Headache Pain . 2017 ;18 (1 ):4 .

    • Search Google Scholar
    • Export Citation
  • 21

    Kalani MY , Turner JD , Nakaji P . Treatment of refractory low-pressure hydrocephalus with an active pumping negative-pressure shunt system . J Clin Neurosci . 2013 ;20 (3 ):462 466 .

    • Search Google Scholar
    • Export Citation
  • 22

    Pandey S , Jin Y , Gao L , et al. Negative-pressure hydrocephalus: a case report on successful treatment under intracranial pressure monitoring with bilateral ventriculoperitoneal shunts . World Neurosurg . 2017 ;99 :812.e7 812.e12 .

    • Search Google Scholar
    • Export Citation
  • 23

    Hatt A , Cheng S , Tan K , et al. MR elastography can be used to measure brain stiffness changes as a result of altered cranial venous drainage during jugular compression . AJNR Am J Neuroradiol . 2015 ;36 (10 ):1971 1977 .

    • Search Google Scholar
    • Export Citation
  • 24

    Wu X , Zang D , Wu X , et al. Diagnosis and management for secondary low- or negative-pressure hydrocephalus and a new hydrocephalus classification based on ventricular pressure . World Neurosurg . 2019 ;124 :e510 e516 .

    • Search Google Scholar
    • Export Citation
  • 25

    Chiang VL , Torbey M , Rigamonti D , Williams MA . Ventriculopleural shunt obstruction and positive-pressure ventilation . Case report. J Neurosurg. 2001 ;95 (1 ):116 118 .

    • Search Google Scholar
    • Export Citation
  • 26

    Smalley ZS , Venable GT , Einhaus S , Klimo P Jr . Low-pressure hydrocephalus in children: a case series and review of the literature . Neurosurgery . 2017 ;80 (3 ):439 447 .

    • Search Google Scholar
    • Export Citation
  • 27

    McGovern RA , Sheehy JP , McKhann GM II . Low pressure hydrocephalus acutely following sepsis and cardiovascular collapse . Clin Neurol Neurosurg . 2013 ;115 (10 ):2186 2188 .

    • Search Google Scholar
    • Export Citation
  • 28

    Foster KA , Deibert CP , Choi PA , et al. Endoscopic third ventriculostomy as adjunctive therapy in the treatment of low-pressure hydrocephalus in adults . Surg Neurol Int . 2016 ;7 :26 .

    • Search Google Scholar
    • Export Citation
  • 29

    Strand A , Balise S , Leung LJ , Durham S . Low-pressure hydrocephalus: a case report and review of the literature . World Neurosurg . 2018 ;109 :e131 e135 .

    • Search Google Scholar
    • Export Citation
  • 30

    Cheng Z , Wang W , Han Y , et al. Low pressure hydrocephalus: clinical manifestations, radiological characteristics, and treatment . Br J Neurosurg . 2017 ;31 (4 ):410 414 .

    • Search Google Scholar
    • Export Citation
  • 31

    Wilson JT , Hareendran A , Grant M , et al. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale . Stroke . 2002 ;33 (9 ):2243 2246 .

    • Search Google Scholar
    • Export Citation
Illustrations from Marx and Schroeder (pp 318–326). Copyright Henry W. S. Schroeder. Published with permission.

Contributor Notes

Correspondence Mark G. Hamilton: University of Calgary, AB, Canada. mghamilton.hydro@gmail.com.

INCLUDE WHEN CITING Published online July 31, 2020; DOI: 10.3171/2020.4.JNS20476.

M.B.K. and A.M.I. contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

  • View in gallery

    Flowchart of a systematic review of the existing literature (1994–2019) on patients with ALPH.

  • View in gallery

    Proposed algorithm for the diagnosis and treatment of ALPH with a goal of definitive therapy. Three major steps in the algorithm are color-coded: pink (A) = establishment of the ALPH diagnosis; purple (B) = stabilization of the patient; and green (C) = undertaking definitive treatment with an ETV or shunt or both ETV and shunt. Red = permanent CSF diversion and resolution of ALPH.

  • 1

    Rekate HL . A contemporary definition and classification of hydrocephalus . Semin Pediatr Neurol . 2009 ;16 (1 ):9 15 .

  • 2

    Kahle KT , Kulkarni AV , Limbrick DD Jr , Warf BC . Hydrocephalus in children . Lancet . 2016 ;387 (10020 ):788 799 .

  • 3

    Leinonen V , Vanninen R , Rauramaa T . Cerebrospinal fluid circulation and hydrocephalus . Handb Clin Neurol . 2017 ;145 :39 50 .

    • Search Google Scholar
    • Export Citation
  • 4

    Cowan JA , McGirt MJ , Woodworth G , et al. The syndrome of hydrocephalus in young and middle-aged adults (SHYMA) . Neurol Res . 2005 ;27 (5 ):540 547 .

    • Search Google Scholar
    • Export Citation
  • 5

    Ono K , Hatada J , Yamada M . Long-standing overt ventriculomegaly in adults (LOVA) needing ventriculo-peritoneal shunt with double programmable pressure valves. Article in Japanese . No Shinkei Geka . 2012 ;40 (1 ):37 42 .

    • Search Google Scholar
    • Export Citation
  • 6

    Mori E , Ishikawa M , Kato T , et al. Guidelines for management of idiopathic normal pressure hydrocephalus: second edition . Neurol Med Chir (Tokyo) . 2012 ;52 (11 ):775 809 .

    • Search Google Scholar
    • Export Citation
  • 7

    Relkin N , Marmarou A , Klinge P , et al. Diagnosing idiopathic normal-pressure hydrocephalus . Neurosurgery . 2005 ;57 (3 )(suppl):S4 S16 , ii–v .

    • Search Google Scholar
    • Export Citation
  • 8

    Bräutigam K , Vakis A , Tsitsipanis C . Pathogenesis of idiopathic normal pressure hydrocephalus: a review of knowledge . J Clin Neurosci . 2019 ;61 :10 13 .

    • Search Google Scholar
    • Export Citation
  • 9

    Hamilton MG , Price AV . Syndrome of inappropriately low-pressure acute hydrocephalus (SILPAH) . Acta Neurochir Suppl (Wien) . 2012 ;113 :155 159 .

    • Search Google Scholar
    • Export Citation
  • 10

    Pang D , Altschuler E . Low-pressure hydrocephalic state and viscoelastic alterations in the brain . Neurosurgery . 1994 ;35 (4 ):643 656 .

    • Search Google Scholar
    • Export Citation
  • 11

    Vassilyadi M , Farmer JP , Montes JL . Negative-pressure hydrocephalus . J Neurosurg . 1995 ;83 (3 ):486 490 .

  • 12

    Filippidis AS , Kalani MY , Nakaji P , Rekate HL . Negative-pressure and low-pressure hydrocephalus: the role of cerebrospinal fluid leaks resulting from surgical approaches to the cranial base . J Neurosurg . 2011 ;115 (5 ):1031 1037 .

    • Search Google Scholar
    • Export Citation
  • 13

    Moher D , Liberati A , Tetzlaff J , Altman DG . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement . Int J Surg . 2010 ;8 (5 ):336 341 .

    • Search Google Scholar
    • Export Citation
  • 14

    O’Hayon BB , Drake JM , Ossip MG , et al. Frontal and occipital horn ratio: a linear estimate of ventricular size for multiple imaging modalities in pediatric hydrocephalus . Pediatr Neurosurg . 1998 ;29 (5 ):245 249 .

    • Search Google Scholar
    • Export Citation
  • 15

    Owler BK , Jacobson EE , Johnston IH . Low pressure hydrocephalus: issues of diagnosis and treatment in five cases . Br J Neurosurg . 2001 ;15 (4 ):353 359 .

    • Search Google Scholar
    • Export Citation
  • 16

    Weed LH . Some limitations of the Monro-Kellie hypothesis . Arch Surg . 1929 ;18 (4 ):1049 1068 .

  • 17

    Olivero WC , Wszalek T , Wang H , et al. Magnetic resonance elastography demonstrating low brain stiffness in a patient with low-pressure hydrocephalus: case report . Pediatr Neurosurg . 2016 ;51 (5 ):257 262 .

    • Search Google Scholar
    • Export Citation
  • 18

    Rekate HL , Nadkarni TD , Wallace D . The importance of the cortical subarachnoid space in understanding hydrocephalus . J Neurosurg Pediatr . 2008 ;2 (1 ):1 11 .

    • Search Google Scholar
    • Export Citation
  • 19

    Dias MS , Li V , Pollina J . Low-pressure shunt ‘malfunction’ following lumbar puncture in children with shunted obstructive hydrocephalus . Pediatr Neurosurg . 1999 ;30 (3 ):146 150 .

    • Search Google Scholar
    • Export Citation
  • 20

    Lin JP , Zhang SD , He FF , et al. The status of diagnosis and treatment to intracranial hypotension, including SIH . J Headache Pain . 2017 ;18 (1 ):4 .

    • Search Google Scholar
    • Export Citation
  • 21

    Kalani MY , Turner JD , Nakaji P . Treatment of refractory low-pressure hydrocephalus with an active pumping negative-pressure shunt system . J Clin Neurosci . 2013 ;20 (3 ):462 466 .

    • Search Google Scholar
    • Export Citation
  • 22

    Pandey S , Jin Y , Gao L , et al. Negative-pressure hydrocephalus: a case report on successful treatment under intracranial pressure monitoring with bilateral ventriculoperitoneal shunts . World Neurosurg . 2017 ;99 :812.e7 812.e12 .

    • Search Google Scholar
    • Export Citation
  • 23

    Hatt A , Cheng S , Tan K , et al. MR elastography can be used to measure brain stiffness changes as a result of altered cranial venous drainage during jugular compression . AJNR Am J Neuroradiol . 2015 ;36 (10 ):1971 1977 .

    • Search Google Scholar
    • Export Citation
  • 24

    Wu X , Zang D , Wu X , et al. Diagnosis and management for secondary low- or negative-pressure hydrocephalus and a new hydrocephalus classification based on ventricular pressure . World Neurosurg . 2019 ;124 :e510 e516 .

    • Search Google Scholar
    • Export Citation
  • 25

    Chiang VL , Torbey M , Rigamonti D , Williams MA . Ventriculopleural shunt obstruction and positive-pressure ventilation . Case report. J Neurosurg. 2001 ;95 (1 ):116 118 .

    • Search Google Scholar
    • Export Citation
  • 26

    Smalley ZS , Venable GT , Einhaus S , Klimo P Jr . Low-pressure hydrocephalus in children: a case series and review of the literature . Neurosurgery . 2017 ;80 (3 ):439 447 .

    • Search Google Scholar
    • Export Citation
  • 27

    McGovern RA , Sheehy JP , McKhann GM II . Low pressure hydrocephalus acutely following sepsis and cardiovascular collapse . Clin Neurol Neurosurg . 2013 ;115 (10 ):2186 2188 .

    • Search Google Scholar
    • Export Citation
  • 28

    Foster KA , Deibert CP , Choi PA , et al. Endoscopic third ventriculostomy as adjunctive therapy in the treatment of low-pressure hydrocephalus in adults . Surg Neurol Int . 2016 ;7 :26 .

    • Search Google Scholar
    • Export Citation
  • 29

    Strand A , Balise S , Leung LJ , Durham S . Low-pressure hydrocephalus: a case report and review of the literature . World Neurosurg . 2018 ;109 :e131 e135 .

    • Search Google Scholar
    • Export Citation
  • 30

    Cheng Z , Wang W , Han Y , et al. Low pressure hydrocephalus: clinical manifestations, radiological characteristics, and treatment . Br J Neurosurg . 2017 ;31 (4 ):410 414 .

    • Search Google Scholar
    • Export Citation
  • 31

    Wilson JT , Hareendran A , Grant M , et al. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale . Stroke . 2002 ;33 (9 ):2243 2246 .

    • Search Google Scholar
    • Export Citation

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