Pituicytoma

Pituicytoma

In 2017, changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma 1).

Pituicytoma is a rare gliasellar/suprasellar neoplasm arising in the neurohypophysis with a possible origin from the folliculostellate cells of the adenohypophysis which are non-endocrine spindled cells expressing S-100 and Bcl-2 2) 3).

Pituicytoma is considered to be a distinct Grade I neoplasm 4).

Although usually intra-sellar, pituicytomas can have suprasellar extension; however, purely suprasellar examples although rare have been reported 5).

PTs had a higher prevalence in the fifth and sixth decades of life, with a slight male predominance. 6)7)

The presenting symptoms are due to the mass effect of the tumor and include visual disturbances caused by direct compression on the optic chiasm, headaches, endocrinological symptoms and rarely diabetes insipidus 8).

Pituicytoma Diagnosis

TTF-1 Expressing Sellar Neoplasm with Ependymal Rosettes and Oncocytic Change: Mixed Ependymal and Oncocytic Variant 9).

When small, and clearly localized to the infundibulum the main differential includes:

granular cell tumors of the pituitary region

craniopharyngioma

When larger, then it is difficult to anticipate the diagnosis with other diagnoses being far more common, including:

pituitary macroadenoma

meningioma

pituitary metastasis

pituitary infiltration

lymphocytic hypophysitis

neurosarcoidosis

optic pathway glioma


Absent Rosenthal fibers and eosinophilic granular bodies, usually help to distinguish between pituicytomas and pilocytic astrocytomas 10).


Amongst the various sellar tumors, pituicytoma and spindle cell oncocytoma (SCO) have considerable overlap in histological, Immunohistochemical (IHC) profile and can have extensive intraoperative bleeding making complete excision difficult with increased chances of recurrence. It is important to differentiate pituicytoma from SCO since the former is associated with a slightly better prognosis with recurrence being uncommon after complete surgical excision. Till 2013, out of 29 cases of pituicytoma with a detailed follow-up, recurrence was seen in six cases, all of which were found to have an incomplete resection during the first surgery 11).

SCO on the other hand have a tendency to recur even after complete excision. Hence, it is advocated to combine surgery with adjuvant radiotherapy in all cases of SCO to reduce the chances of recurrence. EMA is strongly positive in SCO, thus it can help to differentiate pituicytoma from SCO 12).

see Pituicytoma treatment.

Less than 50 cases have been reported in the world literature till 2013 13).

Salge-Arrieta et al., from the Ramón y Cajal University Hospital MadridSpain, published a retrospective review of case reports published in the scientific literature to 2018, including a new illustrative example treated.

116 cases were collected. PTs had a higher prevalence in the fifth and sixth decades of life, with a slight male predominance. Main symptoms, which tended to be progressive, included visual field defects and pituitary-hypothalamic dysfunction. Radiologically, PTs were found anywhere along the hypothalamic-pituitary axis mimicking other, more frequent tumors growing in this anatomical region. Surgical treatment included both transcranial or transsphenoidal approaches, and resulted in gross total resection and morbidity rates of 46.8 and 59%, respectively; the latter essentially consisted in anterior and posterior pituitary dysfunction, with limited impact on daily quality of life.

Due to both low frequency and the absence of pathognomonic clinical and/or radiological features, formulating a suspicion diagnosis of PT represents a considerable challenge even for experienced professionals. The indication for treatment should be made on an individual basis, but it is inescapable in the presence of a visual field defect. The surgical approach has to be tailored according to the topography of the tumor and preoperative symptoms; the greatest challenges in accomplishing a gross total removal are represented by the degree of adherence and vascularization of the PT 14).

Pituicytoma Case Series.


1)

Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017 Oct;134(4):521-535. doi: 10.1007/s00401-017-1769-8. Epub 2017 Aug 18. Review. PubMed PMID: 28821944.
2)

Phillips JJ, Misra A, Feuerstein BG, Kunwar S, Tihan T. Pituicytoma: Characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure, and array-based comparative genomic hybridization. Arch Pathol Lab Med 2010;134:1063-9.
3)

Koutourousiou M, Gardner PA, Kofler JK, Fernandez-Miranda JC, Snyderman CH, Lunsford LD. Rare infundibular tumors: clinical presentation, imaging findings, and the role of endoscopic endonasal surgery in their management. J Neurol Surg B Skull Base. 2013 Feb;74(1):1-11. doi: 10.1055/s-0032-1329619. Epub 2012 Dec 31. PubMed PMID: 24436883; PubMed Central PMCID: PMC3699169.
4)

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97-109.
5)

Zhang F, Chen J, You C. Pituicytoma: Case report and review of the literature. Neurol India 2010;58:799-801.
6) , 14)

Salge-Arrieta FJ, Carrasco-Moro R, Rodríguez-Berrocal V, Pian H, Martínez-San Millán JS, Iglesias P, Ley-Urzáiz L. Clinical features, diagnosis and therapy of pituicytoma: an update. J Endocrinol Invest. 2018 Jul 20. doi: 10.1007/s40618-018-0923-z. [Epub ahead of print] Review. PubMed PMID: 30030746.
7)

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK “WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised” ISBN: 9789283244929
8)

Chu J, Yang Z, Meng Q, Yang J. Pituicytoma: Case report and literature review. Br J Radiol 2011;84:e55-7.
9)

Saeed Kamil Z, Sinson G, Gucer H, Asa SL, Mete O. TTF-1 Expressing Sellar Neoplasm with Ependymal Rosettes and Oncocytic Change: Mixed Ependymal and Oncocytic Variant Pituicytoma. Endocr Pathol. 2013 Nov 16. [Epub ahead of print] PubMed PMID: 24242699.
10)

Nakasu Y, Nakasu S, Saito A, Horiguchi S, Kameya T. Pituicytoma. Two case reports. Neurol Med Chir (Tokyo). 2006 Mar;46(3):152-6. doi: 10.2176/nmc.46.152. PMID: 16565586.
11) , 12)

Ogiwara H, Dubner S, Shafizadeh S, Raizer J, Chandler JP. Spindle cell oncocytoma of the pituitary and pituicytoma: Two tumors mimicking pituitary adenoma. Surg Neurol Int 2011;2:116.
13)

Shenoy AS, Desai HM, Mehta JK. Pituicytoma: a case report with literature revisited. Indian J Pathol Microbiol. 2013 Apr-Jun;56(2):180-1. doi: 10.4103/0377-4929.118695. PubMed PMID: 24056664.

Fluorescein sodium guided resection of high-grade glioma

Fluorescein sodium guided resection of high-grade glioma

Naik et al. compared 5 aminolevulinic acid fluorescence guided resection of high-grade gliomaFluorescein sodium guided resection of high-grade glioma. (FS), and Intraoperative magnetic resonance imaging-guided resection of high-grade glioma (IMRI) with no image guidance to determine the best intraoperative navigation method to maximize rates of gross total resection (GTR) and outcomes. A frequentist network meta-analysis was performed following standard PRISMA guidelines (PROSPERO registration CRD42021268659). Surface-under-the-cumulative ranking (SUCRA) analysis was executed to hierarchically rank modalities by the outcome of interestHeterogeneity was measured by the I2 statisticPublication bias was assessed by funnel plots and the use of Egger’s test. Statistical significance was determined by p < 0.05. Twenty-three studies were included for analysis with a total of 2,643 patients. Network meta-analysis comparing 5-ALA, IMRI, and FS was performed. The primary outcome assessed was the rate of GTR. Analysis revealed the superiority of all intraoperative navigation to control (no navigation). SUCRA analysis revealed the superiority of IMRI + 5-ALA, IMRI alone, followed by FS, and 5-ALA. Overall survival (OS) and progression-free survival (PFS) were also examined. FS (vs. control) was associated with improved OS, while IMRI was associated with improved PFS (vs. control, FS, and 5-ALA). Intraoperative navigation using IMRI, FS, and 5-ALA lead to greater rates of GTR in HGGs. FS and 5-ALA also yielded improvement in OS and PFS. Further studies are needed to evaluate differences in survival benefit, operative duration, and cost 1).


Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed 2).

5-ALA fluorescence-guided surgery has shortcomings such as drug’s phototoxicity, extortionate price, and not being approved by Food and Drug Administration, which limited its widespread application.

Due to the above limitations, sodium fluorescein guided surgery had been paid more attention by neurosurgeons than 5-ALA. FL is an easily available and biosafe fluorescein dye with a peak excitation at 465 to 490 nm and emission between 500 and 550 nm and has been used extensively and safely for many years especially in ophthalmology 3) 4).

5 aminolevulinic acid is still the preferred and more established fluorescent dye used during high-grade gliomas resection, with Fluorescein sodium gaining-attention, really cheaper and more ductile alternative 5).

The use of fluorescein fluorescence-guided stereotactic needle biopsy has been shown to improve diagnostic accuracy and to expedite operative procedure in the stereotactic needle biopsy of high-grade gliomas.

see Fluoropen.

The first use of fluorescence for brain tumour surgery was in 1948 by G.E. Moore 6) using fluorescein sodium, a strongly fluorescing and non-toxic (apart from rare anaphylaxis 7) compound). In malignant brain tumours with their inherent blood-brain barrier breakdown, fluorescein is extravasated and might serve to mark tumours.

Today, fluorescein sodium is again under scrutiny 8) 9). using a novel filter system by Zeiss (YELLOW 560) for the microscope. This filter visualises fluorescein and allows good background discrimination. Furthermore, fluorescein can be injected any time and is low in cost. Nevertheless, its use in brain tumour surgery is off-label and thus restricted to clinical studies. Little is known about the best timing of i.v. fluorescein application before resection. Injecting fluorescein too early might result in unspecific propagation with oedema, whereas acute injections might be useful for detecting abnormally perfused tumour tissue. Levels in the blood will be high, especially with acute injections, leading to fluorescence of all perfused brain tissue. Such time-resolved in- formation on the specificity of fluorescein are not available.

Overall, Schwake et al observed no clear value of fluorescein in a small study, which they closed prematurely. Clearly, further work elucidating optimal timing and dosing of fluorescein is warranted. 10)


Sodium fluorescein (SF) was first used for the identification of different types of brain tumors in 1948 11).

Since then, the use of SF and others fluorescent tracers have been described in literature particularly that dealing with glioblastoma multiforme resection 12) 13) 14)

Metastatic lesion were also enhanced by SF 15)16).

Also in skull base tumors 17).

“Fluorescein sodium”, the sodium salt of fluorescein, is used extensively as a diagnostic tool in the field of ophthalmology and optometry, where topical fluorescein is used in the diagnosis of corneal abrasions, corneal ulcers and herpetic corneal infections. It is also used in rigid gas permeable contact lens fitting to evaluate the tear layer under the lens. It is available as sterile single-use sachets containing lint-free paper applicators soaked in fluorescein sodium.

Intravenous or oral fluorescein is used in fluorescein angiography in research and to diagnose and categorize vascular disorders including retinal disease macular degeneration, diabetic retinopathy, inflammatory intraocular conditions, and intraocular tumors. It is also being used increasingly during surgery for brain tumors.

Diluted fluorescein dye has been used to localise multiple muscular ventricular septal defects during open heart surgery and confirm the presence of any residual defects.


Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross total resection (GTR) using high doses of fluorescein sodium under white light. The introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore.

Fluorescein sodium does not appear to selectively accumulate in astrocytoma cells but in extracellular tumor cell rich locations, suggesting that fluorescein is a marker for areas of compromised blood brain barrier within high grade astrocytoma. Fluorescein fluorescence appears to correlate intraoperatively with the areas of MR enhancement, thus representing a practical tool to help the surgeon achieve GTR of the enhancing tumor regions 18).


Magnetic resonance diffusion tensor imaging (MR-DTI) and fluorescein sodium dyeing guiding for surgery of glioma located in brain motor functional areas can increase the gross total resection rate, decrease the paralysis rate caused by surgery, and improve patient quality of life compared with traditional glioma surgery 19).


Intrathecal fluorescein (ITF) is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair 20).


1)

Naik A, Smith EJ, Barreau A, Nyaeme M, Cramer SW, Najafali D, Krist DT, Arnold PM, Hassaneen W. Comparison of fluorescein sodium, 5-ALA, and intraoperative MRI for resection of high-grade gliomas: A systematic review and network meta-analysis. J Clin Neurosci. 2022 Feb 22;98:240-247. doi: 10.1016/j.jocn.2022.02.028. Epub ahead of print. PMID: 35219089.
2)

Hansen RW, Pedersen CB, Halle B, Korshoej AR, Schulz MK, Kristensen BW, Poulsen FR. Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study. J Neurosurg. 2019 Oct 4:1-8. doi: 10.3171/2019.6.JNS191531. [Epub ahead of print] PubMed PMID: 31585425.
3)

Novotny H. R., Alvis D. L. A method of photographing fluorescence in circulating blood in the human retina. Circulation. 1961;24:82–86. doi: 10.1161/01.cir.24.1.82.
4)

Kwan A. S. L., Barry C., McAllister I. L., Constable I. Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience. Clinical and Experimental Ophthalmology. 2006;34(1):33–38. doi: 10.1111/j.1442-9071.2006.01136.x.
5)

Acerbi F, Restelli F, De Laurentis C, Falco J, Cavallo C, Broggi M, Höhne J, Schebesch KM, Schiariti M, Ferroli P. Fluorescent tracers in neurosurgical procedures: an European survey. J Neurosurg Sci. 2018 Jul 17. doi: 10.23736/S0390-5616.18.04494-6. [Epub ahead of print] PubMed PMID: 30014688.
6)

Moore GE, Peyton WT, French LA, Walker WW (1948) The clinical use of fluorescein in neurosurgery; the localization of brain tumors. J Neurosurg 5:392–398
7)

Dilek O, Ihsan A, Tulay H (2011) Anaphylactic reaction after fluo- rescein sodium administration during intracranial surgery. J Clin Neurosci 18:430–431
8)

Acerbi F, Broggi M, Eoli M, Anghileri E, Cuppini L, Pollo B, Schiariti M, Visintini S, Ori C, Franzini A, Broggi G, Ferroli P (2013) Fluorescein-guided surgery for grade IV gli- omas with a dedicated filter on the surgical microscope: pre- liminary results in 12 cases. Acta Neurochir (Wien) 155: 1277–1286
9)

Schebesch KM, Proescholdt M, Höhne J, Hohenberger C, Hansen E, Reimenschneider MJ, Ullrich W, Doenitz C, Schlair J, Lange M, Brawanski A (2013) Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:693–699
10)

Schwake M, Stummer W, Suero Molina EJ, Wölfer J. Simultaneous fluorescein sodium and 5-ALA in fluorescence-guided glioma surgery. Acta Neurochir (Wien). 2015 May;157(5):877-9. doi: 10.1007/s00701-015-2401-0. Epub 2015 Mar 28. PubMed PMID: 25820632.
11) , 15)

Moore GE, Peyton WT, French LA, Walker WW. The clinical use of fluorescein in neurosurgery. J Neurosurg. 1948;5:392–8.
12)

Chae MP, Song SW, Park SH, Park CK. Experience with 5- aminolevulinic Acid in fluorescence-guided resection of a deep sylvian meningioma. J Korean Neurosurg Soc. 2012;52:558–60.
13)

Kuroiwa T, Kajimoto Y, Ohta T. Development of a fluorescein operative microscope for use during malignant glioma surgery: A technical note and preliminary report. Surg Neurol. 1998;50:41–9.
14)

Kuroiwa T, Kajimoto Y, Ohta T. Comparison between operative findings on malignant glioma by a fluorescein surgical microscopy and histological findings. Neurol Res. 1999;21:130–4.
16)

Okuda T, Kataoka K, Taneda M. Metastatic brain tumor surgery using fluorescein sodium: Technical note. Minim Invasive Neurosurg. 2007;50:382–4.
17)

da Silva CE, da Silva JL, da Silva VD. Use of sodium fluorescein in skull base tumors. Surg Neurol Int. 2010;1:70.
18)

Diaz RJ, Dios RR, Hattab EM, Burrell K, Rakopoulos P, Sabha N, Hawkins C, Zadeh G, Rutka JT, Cohen-Gadol AA. Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance. J Neurosurg. 2015 Jun;122(6):1360-9. doi: 10.3171/2015.2.JNS132507. Epub 2015 Apr 3. PubMed PMID: 25839919.
19)

Liu JG, Yang SF, Liu YH, Wang X, Mao Q. Magnetic resonance diffusion tensor imaging with fluorescein sodium dyeing for surgery of gliomas in brain motor functional areas. Chin Med J (Engl). 2013 Jul;126(13):2418-23. PubMed PMID: 23823811.
20)

Raza SM, Banu MA, Donaldson A, Patel KS, Anand VK, Schwartz TH. Sensitivity and specificity of intrathecal fluorescein and white light excitation for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base surgery: a prospective study. J Neurosurg. 2016 Mar;124(3):621-6. doi: 10.3171/2014.12.JNS14995. Epub 2015 Aug 21. PubMed PMID: 26295912.

Idiopathic normal pressure hydrocephalus outcome

Idiopathic normal pressure hydrocephalus outcome

Mild preoperative Idiopathic normal pressure hydrocephalus severity, shorter preoperative symptom duration, good tap test response, and complete disproportionately enlarged subarachnoid space hydrocephalus (DESH) were associated with good short-term postoperative outcome at 1 year. These positive factors may be useful for prediction of short-term surgical outcome in iNPH patients 1)


Comorbid conditions interfere with the ability to assess progression of iNPH and the effectiveness of the shunt. Patient caregivers play a large role in decision-making and clinical course, and should be included when counseling patients 2).

A 2001 meta-analysis of outcomes reported the Idiopathic normal pressure hydrocephalus treatment to have a 29% rate of significant improvement and a 6% significant complication rate 3).

A study in 2005 revealed greater improvements, with 75% of patients (n = 132) seeing postoperative improvements within 24 months of surgery 4), 68% of patients experiencing “very good” or “good” outcomes in a prospective study 5), and 69%–84% of patients seeing improvements by 1 year after surgery in a prospective multicenter study 6).

Studies that have established fixed protocols for follow-up have shown that short- and long-term periods after shunting are determined by many factors. Whereas short-term results were more likely to be influenced by shunt-associated risks, long-term results were independent of factors inherent to the shunt procedure and shunt complications, i.e., death and morbidity related to concomitant cerebrovascular and vascular diseases 7).

In 2013 a total of 64 studies of 3,063 patients were reviewed. Positive improvement following shunt insertion was reported in an average of 71 % of patients with an average 1 % mortality. Results from studies published in the last 5 years showed 82 % improvement following shunt insertion, mortality of 0.2 %, and combined common complications rate of 8.2 % 8).

Analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective 9).


Clinically, patients presenting with early or severe dementia have worse outcome, while those with a primary gait disturbance feature have better results 10) 11).


Clinical improvement of patients with iNPH can be sustained for 5-7 years in some patients, even if shunt revision surgery is needed multiple times. With earlier diagnosis and treatment and the increasing lifespan of the ageing population, the need for long-term follow-up after shunt surgery may be greater than it was in the past. Monitoring, identification and treatment of shunt obstruction is a key management principle 12).

Gait and Incontinence

Postoperative improvement of Gait and Urinary incontinence is obtained at an early stage 13) 14). In contrast, Dementia tends to improve gradually from after the third postoperative month. The family satisfaction increases as the symptom of Dementia improve. The satisfaction of the medical personnel tends to remain high after the first postoperative month 15).

Independent predictors

Independent predictors of improvement are the presence of gait impairment as the dominant symptom and shorter duration of symptoms 16).

see Caregiver burden in idiopathic normal pressure hydrocephalus.


1)

Kimura T, Yamada S, Sugimura T, Seki T, Miyano M, Fukuda S, Takeuchi M, Miyata S, Tucker A, Fujita T, Hashizume A, Izumi N, Kawasaki K, Nakagaki A, Sako K. Preoperative Predictive Factors of Short-Term Outcome in Idiopathic Normal Pressure Hydrocephalus (iNPH). World Neurosurg. 2021 Apr 22:S1878-8750(21)00596-9. doi: 10.1016/j.wneu.2021.04.055. Epub ahead of print. PMID: 33895373.
2)

Subramanian HE, Mahajan A, Sommaruga S, Falcone GJ, Kahle KT, Matouk CC. The subjective experience of patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus. World Neurosurg. 2018 Jul 4. pii: S1878-8750(18)31425-6. doi: 10.1016/j.wneu.2018.06.209. [Epub ahead of print] PubMed PMID: 29981467.
3)

Hebb AO, Cusimano MD: Idiopathic normal pressure hydrocephalus: a systematic review of diagnosis and outcome. Neurosurgery 49:1166–1186, 2001
4) , 16)

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 Oct;57(4):699-705; discussion 699-705. PubMed PMID: 16239882.
5)

Meier U, Kiefer M, Neumann U, Lemcke J: On the optimal opening pressure of hydrostatic valves in cases of idiopathic normal-pressure hydrocephalus: a prospective randomized study with 123 patients. Acta Neurochir Suppl 96:358–363, 2006
6)

Wikkelsø C, Hellström P, Klinge PM, Tans JT: 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 84:562–568, 2013
7)

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 Sep;57(3 Suppl):S40-52; discussion ii-v. Review. PubMed PMID: 16160428.
8)

Toma AK, Papadopoulos MC, Stapleton S, Kitchen ND, Watkins LD. Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus. Acta Neurochir (Wien). 2013 Oct;155(10):1977-80. doi: 10.1007/s00701-013-1835-5. Epub 2013 Aug 23. Review. PubMed PMID: 23975646.
9)

Nakajima M, Miyajima M, Ogino I, Akiba C, Kawamura K, Kurosawa M, Kuriyama N, Watanabe Y, Fukushima W, Mori E, Kato T, Sugano H, Karagiozov K, Arai H. Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus Improves Patient Outcomes: A Nationwide Hospital-Based Survey in Japan. Front Neurol. 2018 Jun 7;9:421. doi: 10.3389/fneur.2018.00421. eCollection 2018. PubMed PMID: 29942280; PubMed Central PMCID: PMC6004916.
10)

Bugalho P, Alves L, Ribeiro O. Normal pressure hydrocephalus: a qualitative study on outcome. Arq Neuropsiquiatr. 2013 Nov;71(11):890-5. doi: 10.1590/0004-282×20130173. PubMed PMID: 24394877.
11)

Poca MA, Mataró M, Matarín M, Arikan F, Junqué C, Sahuquillo J. Good outcome in patients with normal-pressure hydrocephalus and factors indicating poor prognosis. J Neurosurg. 2005 Sep;103(3):455-63. PubMed PMID: 16235677.
12)

Pujari S, Kharkar S, Metellus P, Shuck J, Williams MA, Rigamonti D. Normal pressure hydrocephalus: long-term outcome after shunt surgery. J Neurol Neurosurg Psychiatry. 2008 Nov;79(11):1282-6. doi: 10.1136/jnnp.2007.123620. Epub 2008 Mar 20. PubMed PMID: 18356257.
13)

Savolainen S, Hurskainen H, Paljärvi L, Alafuzoff I, Vapalahti M: Five-year outcome of normal pressure hydrocephalus with or without a shunt: predictive value of the clinical signs, neuropsychological evaluation and infusion test. Acta Neurochir (Wien) 144:515–523, 2002
14) , 15)

Takeuchi T, Goto H, Izaki K, Tamura S, Sasanuma Z, Maeno K, Kikuchi Y, Tomii M, Koizumi Z, Watanabe Z, Numazawa S, Ito Y, Ohara H, Kowada M, Watanabe K. Postoperative patterns of improvement of symptoms and degrees of satisfaction in families of patients after operations for definite idiopathic normal pressure hydrocephalus: a long-term follow-up study]. No Shinkei Geka. 2007 Aug;35(8):773-9. Japanese. PubMed PMID: 17695775.
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