|Year : 2020 | Volume
| Issue : 1 | Page : 10-15
Diagnosis, pathophysiology, and treatment of normal pressure hydrocephalus: A review of current perspectives
Charchit Gupta1, Pushpendra Nath Renjen1, Dinesh Chaudhari1, Anjali Mishra2
1 Institute of Neurosciences, Indraprastha Apollo Hospitals, 1 Critical Care, Max Super Speciality Hospital, New Delhi, India
2 Department of Critical Care, Max Super Speciality Hospital, New Delhi, India
|Date of Submission||28-Jan-2020|
|Date of Acceptance||01-Feb-2020|
|Date of Web Publication||17-Mar-2020|
Pushpendra Nath Renjen
C-85, Anand Niketan, New Delhi - 110 021
Source of Support: None, Conflict of Interest: None
Normal pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia, and urinary incontinence. A critical review of the current prospectives in the diagnosis and treatment of both idiopathic and secondary NPH has been done in our article. NPH is an important cause of potentially reversible dementia, frequent falls, and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors, and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of noninvasive magnetic resonance imaging methods for quantifying cerebral blood flow, in particular arterial spin-labeling, and the frequent association of NPH and obstructive sleep apnea, offer new avenues to understand and treat NPH.
Keywords: Cerebral blood flow, incontinence, normal pressure hydrocephalus, reversible dementia
|How to cite this article:|
Gupta C, Renjen PN, Chaudhari D, Mishra A. Diagnosis, pathophysiology, and treatment of normal pressure hydrocephalus: A review of current perspectives. Apollo Med 2020;17:10-5
|How to cite this URL:|
Gupta C, Renjen PN, Chaudhari D, Mishra A. Diagnosis, pathophysiology, and treatment of normal pressure hydrocephalus: A review of current perspectives. Apollo Med [serial online] 2020 [cited 2020 Sep 19];17:10-5. Available from: http://www.apollomedicine.org/text.asp?2020/17/1/10/280913
| Introduction|| |
Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized clinically by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia, and urinary incontinence., In 1975, a decade after the initial NPH publications, Shenkin et al. reported symptomatic hydrocephalus in adults without increased intracranial pressure (i.e., “normal pressure”) occurring in the absence of other obvious causes. For the first time, they classified these cases as idiopathic NPH (iNPH) and reported that in elderly patients (average age 68 years, range 52–83) with iNPH manifested by cognitive symptoms of “senile dementia,” 64% (18/28) improved after cerebrospinal fluid (CSF) shunting.
The usual NPH classification into iNPH, accounting for about 50% of cases, and secondary NPH (sNPH), resulting from subarachnoid hemorrhage (SAH), meningitis, intracerebral hemorrhage, brain tumor, or head trauma, is not helpful from a practical viewpoint, mainly because the actual pathogenesis of the NPH syndrome remains unclear. Whereas iNPH is primarily observed in adults older than 60 years, sNPH can occur at any age., In both cases, however, men and women are equally affected. Other than ventriculomegaly, there is no definitive pathological or radiological diagnostic findings for NPH, which is frequently over-suspected and under-confirmed, based only on positive response to CSF shunting.
The diagnostic criteria for NPH remain a topic of discussion. The numerous controversies surrounding this disease led to an interesting dichotomy: While some consider the disorder as the most common type of hydrocephalus in adults, while others, especially in recent years, have been advocating against its existence.,,,
| Idiopathic Normal-Pressure Hydrocephalus|| |
Over the years, the term iNPH has been almost indiscriminately used for all individuals who present with “unexplained” ventriculomegaly detected by brain imaging including computed tomography (CT) or magnetic resonance imaging (MRI), associated with the classic triad comprising cognitive impairment, gait disturbance, and incontinence.,,, In reality, the number of “unexplained” cases might vary according to the intensity of the etiological search, including the use of CSF biomarkers and even brain biopsy.
According to the International Guidelines, the following key imaging features should be employed for the diagnosis of NPH:,
- Ventricular enlargement with Evans's index>0.3 [Figure 1]a. Neuroimaging in NPH (a) Axial fluid-attenuated inversion recovery (FLAIR) MRI scan showing a significant ventriculomegaly with increased the Evans' index, the ratio of the maximum width of the frontal horns of the lateral ventricles and maximal internal diameter of the skull at the same level on axial CT or MRI images. In this case, the Evans' index is 0.39 (abnormal > 0.3) (b) T1-weighted coronal gadolinium-enhanced MRI scan showing reduced callosal angle. (c) Axial FLAIR MRI scan revealing enlarged lateral ventricles with the bright signal in the surrounding white matter, suggestive of transependymal edema. (d) Axial FLAIR MRI showing the narrowing of the sulci and subarachnoid spaces over the high convexity and midline surface in the frontoparietal regions.
- Absence of macroscopic obstruction to CSF flow.
- At least one of these supportive features:
|Figure 1: (a) Axial flair MRI brain scan showing ventricular enlargement with Evans's index >0.3, (b) T1 weighted coronal gadolinium enhanced MRI scan showing reduced callosal angle, (c) Axial flair MRI brain scan revealing enlarged lateral ventricles with bright signals in the surrounding white matter suggestive of transependymal edema, (d) Axial flair MRI Brain scan showing narrowing of the sulci and subarachnoid spaces over the high convexity and midline surface in the frontoparietal region of the brain|
Click here to view
- Enlarged temporal horns of the lateral ventricles not entirely due to hippocampus atrophy;
- The callosal angle of 40° or greater [Figure 1]b;
- Periventricular signal changes on CT and MRI due to altered brain water content and not entirely attributable to microvascular ischemic changes or demyelination [Figure 1]c;
- Flow void in the Sylvian aqueduct or fourth ventricle on MRI
The Japanese Guidelines for the diagnosis of NPH did not regard periventricular changes as relevant for the diagnosis, but included two other key imaging features: narrowing of the sulci and subarachnoid spaces over the high convexity and midline surface of the brain [Figure 1]d; and enlarged Sylvian fissures and basal cisterns.,
| Pathophysiology of Idiopathic Normal-Pressure Hydrocephalus|| |
In the original descriptions, Hakim et al. emphasized that ventriculomegaly is the central element in the clinical syndrome due to the hydraulic pressure effect. The explanation is based on Pascal's law of hydrodynamics, whereby the force exerted by the CSF on the walls of the ventricles is equal to the product of the pressure of the fluid and the area of the wall: F =P× A. The force exerted on the ventricles is transmitted centrifugally, compressing the brain and elevating the transmantle pressure, i.e., the difference between ventricular pressure and the pressure over the cerebral convexity. The result is a global decrease in cerebral perfusion from the centrifugal transmantle pressure, given that most of the arterial cerebral blood flow (CBF) is centripetal, i.e., from the subarachnoid space toward the center of the brain.,
Owler and Pickard reviewed studies of cerebral perfusion in hydrocephalus and concluded that multiple methods have shown a consistent decrease in CBF, mainly in the frontal cortex, periventricular white matter, basal ganglia, and thalami.,,,,,, Enhancement of cerebral perfusion in periventricular white matter and basal ganglia has been described after CSF removal or following surgical CSF shunt treatment.,,
Arterial spin-labeling (ASL) perfusion imaging is a novel noninvasive MRI technique that requires neither contrast media nor isotopes to measure CBF. ASL-MRI generates an endogenous contrast by using radiofrequency pulses that “label” water proton spins in blood circulating in carotid and vertebral arteries at the base of the skull. CBF-ASL-MRI images are obtained by subtracting labeled and unlabeled spin exchanges in the brain tissue yielding a map of regional CBF quantified in mL/100 g/min.
It should be noted that the CSF is called “the third circulation” because of the constant interaction between cerebral arterial circulation, CSF circulation, and venous circulation. The concept of intracranial venous hypertension leading to decreased CSF absorption and hydrocephalus is critical to fully understand the pathogenesis of NPH. Venous hypertension in intracranial circulation hinders CSF absorption through the arachnoid villi in the dural sinuses.,,,, Furthermore, it alters intracranial compliance and changes CSF dynamics, affecting the intracranial Windkessel effect from brain viscoelastic properties.,,,
Malm and Eklund described some of the physiological processes potentially involved in iNPH, including reversible dysfunction of neuronal and glial mechanisms; they pointed to increased intracranial pressure pulsatility and CSF outflow resistance as probable triggers. In 2010, Ott et al. correlated the abnormal dilatation of the ventricles with limited re-absorption of CSF – the subsequent stasis being responsible for defective metabolic clearance. Increased aqueductal CSF flow is considered a positive finding in patients with NPH.
Recently, an association between NPH and the glymphatic system has emerged, attempting to link reduced intracranial compliance and diminished arterial pulsations with the inefficient glymphatic flow., If confirmed, this could partially explain the frequent occurrence of dementia as a prominent characteristic of this disorder, as well as the higher incidence of Alzheimer's disease in NPH patients. Nevertheless, iNPH pathogenesis remains unclear.
Very recently, Román et al. found a strong correlation between obstructive sleep apnea (OSA) and NPH. The mechanisms induced by OSA cause almost total absence of rapid eye movement and delta sleep, affecting glymphatic flow; also, sleep-disordered breathing produces cerebral venous hypertension due to increases in central venous pressure. The postulated net result is a decrease in CSF outflow, leading to hydrocephalus. Nocturnal polysomnogram is, therefore, indicated in the evaluation of patients with suspected NPH.
| Diagnosis and Management|| |
NPH is classically defined as a communicating form of hydrocephalus,,, without a fully effective noninvasive treatment.,,,, However, because of the new hydrodynamic concept of hydrocephalus,, as opposed to the classical dichotomy proposed by Dandy,, the use of endoscopic third ventriculostomy (ETV), which is the golden standard for noncommunicating cases, has been reported in selected cases of NPH, as an attempt to restore normal intracranial compliance and pulsatility, normalizing the CSF dynamics.,,,, The results showed an effectiveness rate of ETV ranging from 21% to 72%.,,, Nevertheless, the available data are insufficient to determine whether or not this surgery is superior to ventriculoperitoneal shunt (VPS), the established treatment for NPH.
CSF shunting and subsequent drainage continue to be the first-line therapy for NPH, with the symptoms usually improving after the intervention. Many authors consider the responsiveness to shunting as the main difference between iNPH and sNPH, where clinical improvement is seen in about 50% of individuals with iNPH and in up to 70% of those with sNPH.
| Large-Volume Lumbar Puncture (Tap Test)|| |
A number of physiologically based tests have been developed to identify CSF flow abnormalities and those patients most likely to respond to CSF shunts. The tap test or large-volume lumbar puncture (LVLP) is one of the most disseminated worldwide, for it is easily performed and cost-effective. Adams et al. were the first to describe the improvement of fleeting symptoms in NPH patients who underwent lumbar puncture (LP). Refinement of the technique, however, occurred years later, with Wikkelsø et al. responsible for adding quantitative methods to the procedure to evaluate cognition and gait. The tap test works by temporarily decreasing intraventricular pressure, mimicking the effect of a shunting procedure, allowing the physician to evaluate the patient's response to a substantial (50 ml) CSF removal.
Given the diagnostic uncertainties mentioned earlier, there are major advantages in securing consensus recommendations from a team that includes specialists in neurology, neuropsychology, physical therapy, neuroradiology, and neurosurgery. Moreover, using quantifiable measurements (balance and gait, cognitive test scores, episodes of incontinence, and CBF in mL/100 g/min), allows objective judgment of each of the test components.
The roman protocol for the large-volume lumbar puncture diagnostic test for normal-pressure hydrocephalus is performed as follows
- Cognitive evaluation by neuropsychologist
- Physical therapy evaluation: gait and balance
- Sphincter continence.
MRI brain, noncontrast, with ASL for CBF
Large-volume LP: 50 mL under fluoroscopy
- Repeat pre-LP protocol within 24 h
- Caregiver global impression of change.
On the day before the LVLP, a clinical neuropsychologist evaluates the following cognitive domains: global cognition, memory, orientation, language, praxis, and executive function. Twenty-four hours after the LVLP, the same specialist performs the second evaluation, modified to avoid learning and practice effects.
On the day of admission for the LVLP, a pretrained physical therapist examines the patient gait and balance before the LVLP using the scores from the Tinetti-test 90 and the Berg Balance scale.
During the period of in-hospital observation (24 h), pre- and post-LVLP, the patient's accompanying relative is instructed to notify the nurse if the subject asks to void or to evacuate, or if incontinence occurred. The number of such events in the 24 h pre- and post-LVLP is recorded.
Nonenhanced brain magnetic resonance imaging with cerebral blood flow-arterial spin-labeling
The baseline nonenhanced brain MRI test is performed on the days leading up to the LVLP and is repeated within 24 h after the tap test. It is usually well tolerated; it does not expose the patient to X-ray radiation, requires no intravenous contrast medium, and can be repeated as often as needed. The only limitation is that MRI cannot be performed in patients with cardiac pacemakers or defibrillators.
Large-volume lumbar puncture
A neuroradiologist performs a routine LP under fluoroscopy with an 18- or 20-gauge spinal needle; 6 ideally, a total of 50 mL of CSF is collected. Opening and closing pressures are recorded and CSF laboratory examinations are obtained, including levels of b-Amyloid and Tau protein.
Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, [time-spatial-labeling-inversion-pulse], phase-contrast-MRI and diffusion-tensor-imaging) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects (AEs) with surgical interventions, noninvasive approaches (pharmacological agents) have earned greater interest of scientists, medical professionals, and health-care providers.
The final diagnosis and therapeutic decision should be the professional responsibility of the trained neurologist or neurosurgeon in charge of the patient after considering the results of each component of the tap test. Usually, surgical treatment with the insertion of a VPS is recommended only for patients that present clear improvement in gait post-LVLP, usually with concurrent improvement in bladder control. Few patients show improvement in cognitive evaluation within the 24 h post-LVLP.
For patients considered to be nonsurgical candidates, and for those that decline surgery, the use of acetazolamide (Diamox®) is recommended at relatively low doses (125–500 mg/day). Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, nonsteroidal anti-inflammatory drugs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.
Despite its novel nature and considerable advantages, the Román et al. Protocol can be associated with some drawbacks – predominantly related to cost-effectiveness – such as requiring a multidisciplinary team, multiple procedures, and a 24-h stay in a hospital. The tap test should be performed by trained professionals.
Professionals must be aware that a lack of response on this test does not contraindicate the surgical procedure as was underpinned by Wikkelsø et al. This multicenter European study, which concluded that the tap test is valid for selecting patients for surgery, but not for excluding them from the treatment, was based on a combined CSF dynamic test that included the results of a 50 ml CSF tap test analysis. In this test, patient gait was assessed 3 h after CSF drainage, by measuring the number of steps and seconds needed to walk 10 m at free speed. Furthermore, shunting procedures are not free of complications and can be associated with significant AEs, including subdural hematomas and hygromas, shunt and central nervous system infection, complex partial seizures, over-drainage, and prolonged postoperative delirium. Less common consequences include death and delayed postoperative pneumocephalus.,,
| Recent Brazilian Experience With Normal-Pressure Hydrocephalus and Tap-Test|| |
In 2018, Souza et al. 104 investigated the impact of the CSF tap test on the gait of patients diagnosed with iNPH. The tap test performed involved the removal of CSF for two consecutive days, with a 24-h interval between the LPs. Each procedure removed 30 mL of CSF. The patient's gait was assessed at two-time points: prior to the first LP, and 3 h after the second procedure. The whole test lasted for about 48 h. This study revealed that gait speed was the most responsive parameter to the test.
Souza et al.'s study was critically reviewed by Damasceno in an editorial, where the aforementioned result was found to be in accordance was the available literature. The need to determine whether other postural or gait parameters could better predict response to surgery was reinforced. In addition, Damasceno also supported repeated or continuous 3-day external lumbar drainage (minimum of 150 ml CSF drained daily) as a way to enhance tap test sensitivity (50%–100%) while maintaining a high positive predictive value (80%–100%), compared to the one-tap CSF tap test with low sensitivity (26%–61%).
| Secondary Normal Pressure Hydrocephalus|| |
sNPH encompasses all cases in which an etiology is identified. It has yet to be determined how long after the inciting event, the symptoms must appear to establish a cause-effect relationship, with opinions varying from immediate to delayed onsets., Engel et al. found that an elevated Evans' ratio was the most common radiological finding preceding the onset of symptoms.
In both forms of NPH, the diagnosis remains based on clinical history, neurological examination, and brain imaging, while the treatment is mainly CSF shunt – involving procedures such as ventriculoperitoneal and ventriculoatrial shunts.
A recent review by Daouet al. assessed 64 studies and showed that SAH was the leading cause of sNPH (46.5%), followed by head trauma (29%), intracranial malignancies – and resection surgeries – (6.2%). Intracerebral hemorrhage, Paget's disease, cerebrovascular diseases, aqueductal stenosis, and radiosurgery were responsible for the other cases. Up to 37% of the patients with SAH developed chronic hydrocephalus, and the basal cisterns and arachnoid villi fibrosis may determine NPH development. Posttraumatic hydrocephalus comprises a varied group of injuries that ultimately impairs CSF flow. On the other hand, brain tumors and inflammatory processes, including neurocysticercosis in tropical countries, increase CSF viscosity due to proteins and other products;,, hence, CSF reabsorption by arachnoid granulations is jeopardized, leading to NPH.
| Conclusion|| |
Taking everything into account, the diagnosis of NPH should always be considered when facing a suggestive clinical presentation. This often occurs in the emergency room when routine brain CT in an elderly patient undergoing evaluation for trauma surprisingly discloses ventriculomegaly, or in the evaluation of patients with gait disorders or cognitive decline in outpatient clinics. It is recommended to always search for an etiology and even when one fails to be found, the diagnosis of NPH should be properly and rapidly addressed.
Overall, sNPH is associated with better outcomes, which is partially explained by swift intervention with adequate VPS placement, which remains the first-line of treatment. NPH may still be considered a potentially reversible cause of dementia; however, a randomized, placebo-controlled trial of shunting procedures should be conducted to finally prove – or refute – the true efficacy of surgical interventions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci 1965;2:307-27.
Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. Symptomatic occult hydrocephalus with “normal” cerebrospinal-fluid pressure. A treatable syndrome. N
Engl J Med 1965;273:117-26.
Shenkin HA, Greenberg J, Bouzarth WF, Gutterman P, Morales JO. Ventricular shunting for relief of senile symptoms. JAMA 1973;225:1486-9.
Bradley WG. Normal pressure hydrocephalus: New concepts on etiology and diagnosis. AJNR Am J Neuroradiol 2000;21:1586-90.
Børgesen SE. Conductance to outflow of CSF in normal pressure hydrocephalus. Acta Neurochir (Wien) 1984;71:1-45.
Hebb AO, Cusimano MD. Idiopathic normal pressure hydrocephalus: A systematic review of diagnosis and outcome. Neurosurgery 2001;49:1166-84.
Williams MA, Malm J. Diagnosis and treatment of idiopathic normal pressure hydrocephalus. Continuum (Minneap Minn) 2016;22:579-99.
Saper CB. Is there even such a thing as “Idiopathic normal pressure hydrocephalus”? Ann Neurol 2017;82:514-5.
Daou B, Klinge P, Tjoumakaris S, Rosenwasser RH, Jabbour P. Revisiting secondary normal pressure hydrocephalus: Does it exist? A review. Neurosurg Focus 2016;41:E6.
Espay AJ, Da Prat GA, Dwivedi AK, Rodriguez-Porcel F, Vaughan JE, Rosso M, et al
. Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration. Ann Neurol 2017;82:503-13.
Gupta A, Lang AE. Potential placebo effect in assessing idiopathic normal pressure hydrocephalus. J Neurosurg 2011;114:1428-31.
Marmarou A, Bergsneider M, Klinge P, Relkin N, Black PM. The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57:S17-28.
Damasceno BP. Neuroimaging in normal pressure hydrocephalus. Dement Neuropsychol 2015;9:350-5.
Mori E, Ishikawa M, Kato T, Kazui H, Miyake H, Miyajima M, et al
. Guidelines for management of idiopathic normal pressure hydrocephalus: second edition. Neurol Med Chir (Tokyo) 2012;52:775-809.
Andersson J, Rosell M, Kockum K, Söderström L, Laurell K. Challenges in diagnosing normal pressure hydrocephalus: Evaluation of the diagnostic guidelines. eNeurologicalSci 2017;7:27-31.
Hakim S, Venegas JG, Burton JD. The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: Mechanical interpretation and mathematical model. Surg Neurol 1976;5:187-210.
Hoff J, Barber R. Transcerebral mantle pressure in normal pressure hydrocephalus. Arch Neurol 1974;31:101-5.
Conner ES, Foley L, Black PM. Experimental normal-pressure hydrocephalus is accompanied by increased transmantle pressure. J Neurosurg 1984;61:322-7.
Owler BK, Pickard JD. Normal pressure hydrocephalus and cerebral blood flow: A review. Acta Neurol Scand 2001;104:325-42.
Bateman GA. The pathophysiology of idiopathic normal pressure hydrocephalus: Cerebral ischemia or altered venous hemodynamics? AJNR Am J Neuroradiol 2008;29:198-203.
Owler BK, Momjian S, Czosnyka Z, Czosnyka M, Péna A, Harris NG, et al
. Normal pressure hydrocephalus and cerebral blood flow: A PET study of baseline values. J Cereb Blood Flow Metab 2004;24:17-23.
Owler BK, Pena A, Momjian S, Czosnyka Z, Czosnyka M, Harris NG, et al
. Changes in cerebral blood flow during cerebrospinal fluid pressure manipulation in patients with normal pressure hydrocephalus: A methodological study. J Cereb Blood Flow Metab 2004;24:579-87.
Ziegelitz D, Starck G, Kristiansen D, Jakobsson M, Hultenmo M, Mikkelsen IK, et al
. Cerebral perfusion measured by dynamic susceptibility contrast MRI is reduced in patients with idiopathic normal pressure hydrocephalus. J Magn Reson Imaging 2014;39:1533-42.2.
Momjian S, Owler BK, Czosnyka Z, Czosnyka M, Pena A, Pickard JD. Pattern of white matter regional cerebral blood flow and autoregulation in normal pressure hydrocephalus. Brain 2004;127:965-72.
Luciano MG, Skarupa DJ, Booth AM, Wood AS, Brant CL, Gdowski MJ. Cerebrovascular adaptation in chronic hydrocephalus. J Cereb Blood Flow Metab 2001;21:285-94.
Calamante F. Perfusion MRI using dynamic-susceptibility contrast MRI: Quantification issues in patient studies. Top Magn Reson Imaging 2010;21:75-85.
Virhammar J, Laurell K, Ahlgren A, Cesarini KG, Larsson EM. Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal. J Cereb Blood Flow Metab 2014;34:1771-8.
Vorstrup S, Christensen J, Gjerris F, Sørensen PS, Thomsen AM, Paulson OB. Cerebral blood flow in patients with normal-pressure hydrocephalus before and after shunting. J Neurosurg 1987;66:379-87.
Ziegelitz D, Arvidsson J, Hellström P, Tullberg M, Wikkelsø C, Starck G. In patients with idiopathic normal pressure hydrocephalus postoperative cerebral perfusion changes measured by dynamic susceptibility contrast magnetic resonance imaging correlate with clinical improvement. J Comput Assist Tomogr 2015;39:531-40.
Tuniz F, Vescovi MC, Bagatto D, Drigo D, De Colle MC, Maieron M, et al
. The role of perfusion and diffusion MRI in the assessment of patients affected by probable idiopathic normal pressure hydrocephalus. A cohort-prospective preliminary study. Fluids Barriers CNS 2017;14:24.4.
Yeom KW, Lober RM, Alexander A, Cheshier SH, Edwards MS. Hydrocephalus decreases arterial spin-labeled cerebral perfusion. AJNR Am J Neuroradiol 2014;35:1433-9.
El Sankari S, Gondry-Jouet C, Fichten A, Godefroy O, Serot JM, Deramond H, et al
. Cerebrospinal fluid and blood flow in mild cognitive impairment and Alzheimer's disease: A differential diagnosis from idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 2011;8:12.
Beggs CB. Venous hemodynamics in neurological disorders: An analytical review with hydrodynamic analysis. BMC Med 2013;11:142.
Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 2014;11:10.
Qvarlander S, Ambarki K, Wåhlin A, Jacobsson J, Birgander R, Malm J, et al
. Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus. Acta Neurol Scand 2017;135:576-84.
Satow T, Aso T, Nishida S, Komuro T, Ueno T, Oishi N, et al
. Alteration of venous drainage route in idiopathic normal pressure hydrocephalus and normal aging. Front Aging Neurosci 2017;9:387.
Bateman GA, Siddique SH. Cerebrospinal fluid absorption block at the vertex in chronic hydrocephalus: Obstructed arachnoid granulations or elevated venous pressure? Fluids Barriers CNS 2014;11:11.
Malm J, Eklund A. Idiopathic normal pressure hydrocephalus. Pract Neurol 2006;6:14Y27.
Ott BR, Cohen RA, Gongvatana A, Okonkwo OC, Johanson CE, Stopa EG, et al
. Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer's disease. J Alzheimers Dis 2010;20:647-57.
El Sankari S, Fichten A, Gondry-Jouet C, Czosnyka M, Legars D, Deramond H, et al
. Correlation between tap test and CSF aqueductal stroke volume in idiopathic normal pressure hydrocephalus. Acta Neurochir Suppl 2012;113:43-6.
Oliveira L, Figueiredo E, Peres C. The glymphatic system a review. Arq Bras Neurocir 2018;37:190-5.
Ringstad G, Vatnehol SAS, Eide PK. Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain 2017;140:2691-705.
Cabral D, Beach TG, Vedders L, Sue LI, Jacobson S, Myers K, et al
. Frequency of Alzheimer's disease pathology at autopsy in patients with clinical normal pressure hydrocephalus. Alzheimers Dement 2011;7:509-13.
Román GC, Verma AK, Zhang YJ, Fung SH. Idiopathic normal-pressure hydrocephalus and obstructive sleep apnea are frequently associated: A prospective cohort study. J Neurol Sci 2018;395:164-8.
Bech-Azeddine R, Waldemar G, Knudsen GM, Høgh P, Bruhn P, Wildschiødtz G, et al
. Idiopathic normal-pressure hydrocephalus: Evaluation and findings in a multidisciplinary memory clinic. Eur J Neurol 2001;8:601-11.
McGirt MJ, Woodworth G, Coon AL, Thomas G, Williams MA, Rigamonti D. Diagnosis, treatment, and analysis of long-term outcomes in idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57:699-705.
Klinge P, Marmarou A, Bergsneider M, Relkin N, Black PM. Outcome of shunting in idiopathic normal-pressure hydrocephalus and the value of outcome assessment in shunted patients. Neurosurgery 2005;57:S40-52.
Williams MA. Comment: The trouble with “n” in normal-pressure hydrocephalus. Neurology 2014;82:1350.
Vanneste JA. Diagnosis and management of normal-pressure hydrocephalus. J Neurol 2000;247:5-14.
Nassar B, Lippa C. Idiopathic normal pressure hydrocephalus. Gerontol Geriatr Med 2016. doi: 10.1177/2333721416643702.
Oliveira MF, Reis RC, Trindade EM, Pinto FC. Evidences in the treatment of idiopathic normal pressure hydrocephalus. Rev Assoc Med Bras (1992) 2015;61:258-62.
Bradley WG Jr. Intracranial pressure versus phase-contrast MR imaging for normal pressure hydrocephalus. AJNR Am J Neuroradiol 2015;36:1631-2.
Greitz D. Paradigm shift in hydrocephalus research in legacy of Dandy's pioneering work: Rationale for third ventriculostomy in communicating hydrocephalus. Childs Nerv Syst 2007;23:487-9.
Rekate HL. Comments on the article by D. Greitz “Paradigm shift in hydrocephalus research in legacy of Dandy's pioneering work: Rationale for third ventriculostomy in communicating hydrocephalus”. Childs Nerv Syst 2007;23:1227-8.
Dandy WE. An operative procedure for hydrocephalus. Bull Johns Hopkins Hosp 1922;33:189-90.
Uche EO, Okorie C, Iloabachie I, Amuta DS, Uche NJ. Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in non-communicating hydrocephalus (NCH): Comparison of outcome profiles in Nigerian children. Childs Nerv Syst 2018;34:1683-9.
Del Bigio MR, Di Curzio DL. Nonsurgical therapy for hydrocephalus: A comprehensive and critical review. Fluids Barriers CNS 2016;13:3.
Kandasamy J, Yousaf J, Mallucci C. Third ventriculostomy in normal pressure hydrocephalus. World Neurosurg 2013;79:S22.e1-7.
Tasiou A, Brotis AG, Esposito F, Paterakis KN. Endoscopic third ventriculostomy in the treatment of idiopathic normal pressure hydrocephalus: A review study. Neurosurg Rev 2016;39:557-63.
Gangemi M, Maiuri F, Naddeo M, Godano U, Mascari C, Broggi G, et al
. Endoscopic third ventriculostomy in idiopathic normal pressure hydrocephalus: An Italian multicenter study. Neurosurgery 2008;63:62-7.
Wikkelsø C, Andersson H, Blomstrand C, Lindqvist G. The clinical effect of lumbar puncture in normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry 1982;45:64-9.
Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc 1986;34:119-26.
Berg KO, Wood-Dauphinee SL, Williams JI, Maki B. Measuring balance in the elderly: Validation of an instrument. Can J Public Health 1992;83 Suppl 2:S7-11.
Alperin N, Oliu CJ, Bagci AM, Lee SH, Kovanlikaya I, Adams D, et al
. Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. Neurology 2014;82:1347-51.
Mihalj M, Dolić K, Kolić K, Ledenko V. CSF tap test-Obsolete or appropriate test for predicting shunt responsiveness? A systemic review. J Neurol Sci 2016;362:78-84.
Wikkelsø C, Hellström P, Klinge PM, Tans JT; European iNPH Multicentre Study Group. The European iNPH multicentre study on the predictive values of resistance to CSF outflow and the CSF tap test in patients with idiopathic normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry 2013;84:562-8.
Kotagal V, Walkowiak E, Heth JA. Serious adverse events following normal pressure hydrocephalus surgery. Clin Neurol Neurosurg 2018;170:113-5.
Lemcke J, Meier U, Müller C, Fritsch MJ, Kehler U, Langer N, et al
. Safety and efficacy of gravitational shunt valves in patients with idiopathic normal pressure hydrocephalus: A pragmatic, randomised, open label, multicentre trial (SVASONA). J Neurol Neurosurg Psychiatry 2013;84:850-7.
Verhaeghe A, De Muynck S, Casselman JW, Vantomme N. Delayed intraventricular pneumocephalus following shunting for normal-pressure hydrocephalus. World Neurosurg 2018;116:174-7.
Souza RK, Rocha SF, Martins RT, Kowacs PA, Ramina R. Gait in normal pressure hydrocephalus: Characteristics and effects of the CSF tap test. Arq Neuropsiquiatr 2018;76:324-31.
Damasceno BP. Normal pressure hydrocephalus and the predictive value of presurgical tests. Arq Neuropsiquiatr 2018;76:285-6.
Kazui H, Miyajima M, Mori E, Ishikawa M; SINPHONI-2 Investigators. Lumboperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (SINPHONI-2): An open-label randomised trial. Lancet Neurol 2015;14:585-94.
Chen Z, Song W, Du J, Li G, Yang Y, Ling F. Rehabilitation of patients with chronic normal-pressure hydrocephalus after aneurysmal subarachnoid hemorrhage benefits from ventriculoperitoneal shunt. Top Stroke Rehabil 2009;16:330-8.
Engel DC, Adib SD, Schuhmann MU, Brendle C. Paradigm-shift: Radiological changes in the asymptomatic iNPH-patient to be: An observational study. Fluids Barriers CNS 2018;15:5.
Evans WA Jr. An encephalographic ratio for estimating ventricular enlargement and cerebral atrophy. Arch Neurol Psychiatry 1942;47:931-7.
Pirouzmand F, Tator CH, Rutka J. Management of hydrocephalus associated with vestibular schwannoma and other cerebellopontine angle tumors. Neurosurgery 2001;48:1246-53.
Zhang L, Hussain Z, Ren Z. Recent Advances in rational diagnosis and treatment of normal pressure hydrocephalus: A critical appraisal on novel diagnostic, therapy monitoring and treatment modalities. Curr Drug Targets 2019;20:1041-57.
Oliveira LM, Nitrini R, Román GC. Normal-pressure hydrocephalus: A critical review. Dement Neuropsychol 2019;13:133-43.