Lumbar infusion test for idiopathic normal pressure hydrocephalus diagnosis [Neurosurgery Wiki]

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====== Lumbar infusion test for idiopathic normal pressure hydrocephalus diagnosis ======

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1H77a1bY6297rPJn2SMoLGZ3OlW9qRV54pcurDsclnryUJtgxW/?limit=15&utm_campaign=pubmed-2&fc=20241008032529}}
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[[Idiopathic normal pressure hydrocephalus]], [[secondary chronic hydrocephalus]], and other [[cerebrospinal fluid]] (CSF) [[disorder]]s are often challenging to diagnose. Since [[shunt surgery]] is usually the only therapeutic option and carries significant [[morbidity]], optimal patient selection is crucial. The [[tap test]] is the most commonly used prognostic test to confirm the diagnosis but lacks [[sensitivity]]. The lumbar [[infusion test]] appears to be a better [[option]], offering additional information on brain [[dynamics]] without increasing [[morbidity]]. However, this technique remains underused. In a [[narrative review]], supported by the extensive experience of several European expert [[center]]s, Jannelli et al. detail the physiological basis, indications, and [[cerebrospinal fluid dynamics]] parameters that can be measured. They also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, they discuss the [[limitation]]s and morbidity associated with the LIT. This review aims to assist teams wishing to incorporate LIT into their screening tools for chronic hydrocephalus and other CSF disorders
((Jannelli G, Calvanese F, Pirina A, Gergelé L, Vallet A, Palandri G, Czosnyka M, Czosnyka Z, Manet R. Assessment of CSF Dynamics Using Infusion Study: Tips and Tricks. World Neurosurg. 2024 Sep;189:33-41. doi: 10.1016/j.wneu.2024.05.131. Epub 2024 May 27. PMID: 38810871.))
----


Lumbar [[infusion test]]: Resistance testing is the resistance to outflow of [[cerebrospinal fluid]] (CSF).

[[CSF]] [[ROut]] is considered to be the [[impedance]] of CSF absorptive mechanisms.

1/ROut is the [[conductance]].

Techniques and thresholds are center-specific.

In a study of patients with symptoms of hydrocephalus, but normal ICPs, the increase in Rcsf and decrease in CSF production were most pronounced in patients who were older than 56 years of age. This relationship was more significant than previously suggested
((Czosnyka M, Czosnyka ZH, Whitfield PC, Donovan T, Pickard JD. Age dependence
of cerebrospinal pressure-volume compensation in patients with hydrocephalus. J
Neurosurg. 2001 Mar;94(3):482-6. PubMed PMID: 11235954.
)).

Determination of CSF outflow resistance via an infusion test was found to carry a sensitivity of 57%–100% and a positive predictive value of 75%–92%, whereas prolonged [[External lumbar cerebrospinal fluid drainage]] in excess of 300 ml ([[cerebrospinal fluid tap test]]) was associated with a sensitivity of 50%–100% and a positive predictive value of 80%–100%
((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 57 (3 Suppl):S17–S28, ii–v, 2005))

===== Methodology =====

Numerous methods have been devised to measure [[ROut]].

[[Bolus method]].

[[Katzman Test]].
----

[[Infusion test]]s are used to diagnose and select patients with [[idiopathic normal pressure hydrocephalus]] (INPH) for [[shunt surgery]]. The test characterizes [[cerebrospinal fluid dynamics]] and estimates parameters of the cerebrospinal fluid system, the [[pressure volume index]] (PVI) and the outflow conductance (Cout). 

see [[Oscillating Pressure Infusion]].

Lumbar [[infusion test]] (LIFT) is not an ideal test to exclude patients with suspected [[idiopathic normal pressure hydrocephalus]] from treatment,min concordance with the results of a multicenter trial
((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)).

In a study of Mahr et al. nearly one half of the LIFT predictions based on [[ROut]] would have been false positive
((Mahr CV, Dengl M, Nestler U, Reiss-Zimmermann M, Eichner G, Preuß M,
Meixensberger J. Idiopathic normal pressure hydrocephalus: diagnostic and
predictive value of clinical testing, lumbar drainage, and CSF dynamics. J
Neurosurg. 2016 Jan 29:1-7. [Epub ahead of print] PubMed PMID: 26824377.
)).

An assessment of Hakim's triad was performed, together with an analysis of radiological parameters and the results of lumbar infusion tests (LITs), both on admission and at the later date (on average, after 5.6 months). All parameters were analyzed with respect to periventricular lucency (PVL), atrophy, type of NPH, and the age of the patients.

There were no deteriorations and six patients improved. Those who were over 50 and who had no PVL or secondary NPH tended to improve more frequently. Significant improvement of dementia was noted (p = 0.042) in all cases, and in the group of patients without PVL (p = 0.04). The size of the ventricles did not change significantly. The values of the resistance to outflow (R), elastance (E), and ICP remained stable.

Analysis of this series revealed that the patients suspected of having NPH who had not been qualified for shunting did not deteriorate, while some of them even improved significantly as far as the level of dementia was concerned. As the CT and LIT parameters remained stable, there were no indications for repeating these examinations, at least within the period of nearly 6 months, which followed the primary diagnosis
((Czepko R, Cieslicki K. Repeated assessment of suspected normal pressure
hydrocephalus in non-shunted cases. A prospective study based on the constant
rate lumbar infusion test. Acta Neurochir (Wien). 2016 May;158(5):855-63. doi:
10.1007/s00701-016-2732-5. Epub 2016 Feb 29. PubMed PMID: 26923798.
)).

===== ROut =====
[[ROut]]

===== Slope until reaching the plateau =====
[[Slope until reaching the plateau]]
===== Case series =====

A single-center cohort study of prospectively collected data of 96 patients who underwent [[Lumbar Infusion Test]] and 5-day [[External lumbar cerebrospinal fluid drainage]]) as a [[reference]] diagnostic [[method]]. A set of selected 48 intracranial pressure/electrocardiogram complex signal waveform features describing nonlinear behavior, wavelet transforms spectral signatures, or recurrent map patterns were calculated for each patient. After applying a [[Leave-One-Out Cross-Validation]] training-testing split of the data set, they trained and evaluated the performance of various state-of-the-art ML algorithms.

The highest-performing [[Machine learning algorithm]] was the Extreme Gradient Boosting. This model showed good calibration and discrimination on the testing data, with an area under the receiver operating characteristic curve of 0.891 (accuracy: 82.3%, sensitivity: 86.1%, and specificity: 73.9%) obtained for 8 selected features. Our ML model clearly outperforms the classical Rout-based manual classification commonly used in clinical practice with an accuracy of 62.5%.

This study successfully used the ML approach to predict the outcome of a 5-day [[External lumbar cerebrospinal fluid drainage]] and hence which patients are likely to benefit from permanent [[shunt]] [[implantation]]. Theser automated ML model thus enhances the diagnostic utility of LIT in the management
((Mládek A, Gerla V, Skalický P, Vlasák A, Zazay A, Lhotská L, Beneš V Sr, Beneš V Jr, Bradáč O. Prediction of Shunt Responsiveness in Suspected Patients With Normal Pressure Hydrocephalus Using the Lumbar Infusion Test: A Machine Learning Approach. Neurosurgery. 2022 Jan 28. doi: 10.1227/NEU.0000000000001838. Epub ahead of print. PMID: 35080523.)).
===2016===
Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, [[lumbar infusion test]] (LIFT), and ELD for 24-72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. 

Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini-Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF ([[ROut]]) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). Despite a multitude of invasive tests, presurgical clinical testing and response to ELD yielded the best prediction for improvement of symptoms following surgery. The complication rate of invasive testing was 5.4%. Multiple and simple linear regression analyses indicated that outcome can only be predicted by a combination of parameters, in accordance with a multifactorial pathogenesis of iNPH
((Mahr CV, Dengl M, Nestler U, Reiss-Zimmermann M, Eichner G, Preuß M,
Meixensberger J. Idiopathic normal pressure hydrocephalus: diagnostic and
predictive value of clinical testing, lumbar drainage, and CSF dynamics. J
Neurosurg. 2016 Jan 29:1-7. [Epub ahead of print] PubMed PMID: 26824377.
)).

=== 2005 ===


Recordings from preoperative LIT in 55 patients were scrutinized for the values of P(pl), P(plA), v(P) and R(out). Gait, memory, spatial capacity and reaction ability were tested before and 6 months after shunt surgery.
RESULTS:

Forty-three (78%) of the patients improved. There were no statistically significant differences in P(pl), R(out), P(plA) or v(P) between improved and not improved patients. Five patients with P(pl) below 22 mmHg (the cut off level) improved after shunting, while 16 and eight patients with R(out) below the cut off levels of 18 and 14 mmHg/ml/min improved. P(plA) correlated with P(pl) and R(out) (r = 0.74 and 0.63, respectively). In the group of patients with high P(plA) (>/=20 mmHg) as many as 93% improved but a high P(plA) did not recruit more improved patients than P(pl) or R(out) alone.
CONCLUSION:

v(P) or P(plA) does not add useful information to P(pl) for selecting patients with suspected NPH for surgery. R(out) calculations from LIT does not provide advantage over using the steady-state plateau pressure for selecting patients for surgery and may increase the risk of missing patients who should benefit from surgery
((Kahlon B, Sundbärg G, Rehncrona S. Lumbar infusion test in normal pressure
hydrocephalus. Acta Neurol Scand. 2005 Jun;111(6):379-84. PubMed PMID: 15876339.
)).
----
[[Infusion test]] of [[saline]] through [[LP]] at a known rate, [[Rout]] is given by Eq:

Final steady stat pressure- Initial pressure/ Infusion rate
((Katzman R, Hussey F. A simple constant-infusion manometric test for
measurement of CSF [[absorption]]. I. Rationale and method. Neurology. [[1970]]
Jun;20(6):534-44. PubMed PMID: 5463608.)).
----

Up to 19 % of patients experience headache after [[infusion]] studies
((Meier U, Bartels P. The importance of the intrathecal infusion test in the
diagnostic of normal-pressure hydrocephalus. Eur Neurol. 2001;46(4):178-86.
PubMed PMID: 11721123.
)).

===== Case series =====

==== 2013 ====
Cordero Tous et al., prospectively analysed 40 patients. The diagnosis of [[idiopathic normal pressure hydrocephalus]] was established when patients met 3 criteria: (i)clinical; (ii)radiological (Evans >0.3), and (iii)hydrodynamic (Katzman infusion test with Rout >12) or pathological ICP monitoring (B waves in over 20% of a nocturnal registration). We used a low-pressure DVP 5/35 [[GAV]] in all cases. Clinical assessments were conducted at 3, 6 and 12 months and radiological assessments at 6 months postoperatively. The clinical improvement of patients was assessed with the NPH, modified RANKIN and modified PFEIFFER rating scales.

The study of risk factors (age, gender, smoking, drinking, arterial hypertension, diabetes mellitus, dyslipidemia) did not establish statistically significant relationships. A statistically significant improvement was observed (P<.01) in the NPH and RANKIN tests at 3, 6 and 12 months. Clinical improvement values obtained were: NPH 73%, 74% and 64%, and RANKIN 54%, 72% and 56%, respectively. The PFEIFFER scale only showed a significant improvement at 12 months. These improvements were classified into various levels (high, moderate, mild and no improvement). The initial mean Evans index was 0.385, and 0.3675 postoperatively. There was only one infection of the valvular system (2%) without further complications. Morbidity and mortality related to the procedure were 0%.

An appropriate selection of patients through clinical, radiological, hydrodynamic and ICP monitoring criteria enables us to obtain good results and a low complication rate
((Cordero Tous N, Román Cutillas AM, Jorques Infante AM, Olivares Granados G,
Saura Rojas JE, Iañez Velasco B, Sánchez Corral C, Roldán Serrano MÁ, Horcajadas 
Almansa A. [Adult chronic idiopathic hydrocephalus-diagnosis, treatment and
evolution. Prospective study]. Neurocirugia (Astur). 2013 May-Jun;24(3):93-101.
doi: 10.1016/j.neucir.2011.12.007. Epub 2013 Mar 22. Spanish. PubMed PMID:
23523476.
)).

==== 2001 ====

Between May 1982 and January 1997, Meier and Bartels investigated 200 patients suspected of having NPH by carrying out an intrathecal infusion test with a constant-flow technique. The resistance to cerebrospinal fluid outflow in the intrathecal infusion test was the main criterion for grouping patients into those with NPH or those with cerebral atrophy. A further differentiation into early stage and advanced stage was made by measuring the compliance, this being the secondary criterion.

In 107 patients (54%), the diagnosis of NPH could be confirmed. Of these, 102 patients (95%) underwent a shunt operation. Graduation of NPH and cerebral atrophy following the results of the infusion test at an early stage and an advanced stage allows prognostic evaluations about the course of disease to be made. Patients with NPH at an early stage reported an improvement of their symptoms in the follow-up after a shunt operation in 65% of cases, while 50% of those with advanced-stage NPH reported improvement.

The computer- aided infusion test allows a reliable differentiation between patients with NPH and those with cerebral atrophy
((Meier U, Bartels P. The importance of the intrathecal infusion test in the
diagnostic of normal-pressure hydrocephalus. Eur Neurol. 2001;46(4):178-86.
PubMed PMID: 11721123.
)).

==== 1992 ====
Over 12-months 17 patients were admitted to the hospital for the presumed diagnosis of normal pressure hydrocephalus (NPH). Four patients had cardinal signs of the syndrome: gait disturbance, dementia and urinary incontinence. Six patients had gait disturbance and dementia. Five patients had gait disturbance and ventricular enlargement on CT scans of the brain, while the last two patients had only urinary incontinence and dementia. All patients underwent neurological examination and CT scans. Clinical and radiological results of these patients were compared with the results of the Katzman's test. Katzman's test was performed in all patients. Physiologic solution of 0.9% NaCl was infused in the lumbal subarachnoid space. The rate of infusion was 1 ml/min during 60 minutes. Cerebrospinal fluid (CSF) pressure was recorded simultaneously using metal aneroid. The test was considered positive if either CSF pressure over 300 mm H2 or undulating waves were recorded at any time of the test. Katzman's test was positive in 12 patients (9 of them with NPH). The undulating waves were recorded in 6 patients (5 with NPH). Four of them experienced tachycardia, hyperventilation, cephalea and mild confusion during the test. The test was positive in all 9 patients with NPH but also in 3 patients with different but pathophysiologically similar disorders. The test was positive in all 4 patients with the characteristic clinical triad of the syndrome and also in all 4 patients with periventricular hypodensity on their CT scans. No patient without gait disturbance had positive test. All except one patient with focal signs or pronounced cortical atrophy, besides with dramatic clinical improvement
((Sokić DV, Kostić VS, Ocić GG, Lević ZM. [The intrathecal manometric lumbar
infusion test (Katzman Test) in the diagnosis of normotensive hydrocephalus]. Srp
Arh Celok Lek. 1992 Jan-Feb;120(1-2):39-47. Serbian. PubMed PMID: 1641699.
)).