This document summarizes a student seminar presentation about normal pressure hydrocephalus (NPH). NPH is caused by excess cerebrospinal fluid in the brain and presents as a triad of symptoms - abnormal gait, urinary incontinence, and dementia. Diagnosis involves MRI/CT showing ventricle enlargement. Treatment is typically a shunt to drain excess fluid. An alternative treatment, endoscopic third ventriculostomy, is gaining interest. A recent study found that lower levels of a cerebrospinal fluid protein correlate with the DESH subtype of NPH and could serve as a diagnostic biomarker.

1. Normal pressure
hydrocephalus
A student seminar
Bshr Nammouz - 3’rd year Medical School - SSST

2. Overview

3. Normal pressure hydrocephalus is:
a clinical symptom complex caused
by the build-up of cerebrospinal
fluid.
T2-weighted MRI showing dilatation of
ventricles out of proportion to
sulcal atrophy in a patient with
normal pressure hydrocephalus. The
arrow points to transependymal flow.
Medscape.

4. Clinical triad:
1- Abnormal gait.
2- Urinary incontinence.
3- Dementia.
3 Ws:
Wobbly
Wet
Wacky

5. More
details:
1. Abnormal gait: Earliest feature and most
responsive to treatment; bradykinetic,
broad-based, magnetic, and shuffling gait.
2. Urinary incontinence: Urinary frequency,
urgency, or frank incontinence.
3. Dementia: Prominent memory loss and
bradyphrenia; forgetfulness, decreased
attention, inertia.

6. ● A gradually progressive disorder.
● A disease of the elderly, The following Norwegian study
showed the incidence and prevalence of NPH increasing
with age.

8. Causes:
● Idiopathic in 50% of patients.
● Secondary causes of NPH include head injury, subarachnoid
hemorrhage, meningitis, and CNS tumor. Another potential
cause could be previously compensated congenital
hydrocephalus.

9. Diagnostic considerations:
Multiple other illnesses may present
similarly to NPH.
In particular, Parkinson disease and NPH may
present in a similar, but distinct manner.
Start hesitation and freezing episodes can
occur in NPH, often mimicking the gait in
Parkinson disease. In contrast to Parkinson
disease, rigidity and unilateral rest tremor
are less commonly observed. Furthermore, a
robust response to L-Dopa is not typically
seen in NPH, in contrast to Parkinson
disease.
Looks similar to AD
and Parkinson, But:
Unlike them, it is
treatable

10. Criteria to establish diagnosis:
An MRI or CT must show an Evan’s
index of at least 0.3. In addition,
one or more of the following must
also be present:
● Temporal horn enlargement
● Periventricular signal changes
● Periventricular edema
● Aqueductal/fourth ventricular
flow void

11. Surgical care:
An ideal candidate for shunt surgery would show imaging evidence of
ventriculomegaly indicated by a frontal horn ratio exceeding 0.50 on imaging
studies along with one or more of the following criteria:
● Presence of a clearly identified etiology
● Predominant gait difficulties with mild or absent cognitive impairment
● Substantial improvement after CSF withdrawal (CSF tap test or lumbar
drainage)
● Normal-sized or occluded sylvian fissures and cortical sulci on CT or MRI
● Absent or moderate white matter lesions on MRI

12. Prospectives

13. An alternative technique to shunt
surgery is gaining some currency. This
involves endoscopic third
ventriculostomy (ETV). Although it has
been previously used in noncommunicating
hydrocephalus, its use has also been
examined in patients with NPH.
A promising
technique

15. ETV technique:
https://www.youtube.com/watch?v=ToYpLn8XEh4
https://www.youtube.com/watch?v=bjGVXYH9mZg

16. A promising study:

17. Background
Idiopathic normal pressure hydrocephalus (iNPH) is a treatable cause of
dementia, gait disturbance, and urinary incontinence in elderly patients with
ventriculomegaly. Its unique morphological feature, called disproportionately
enlarged subarachnoid-space hydrocephalus (DESH), may also be a diagnostic
feature. Lipocalin-type prostaglandin D synthase (L-PGDS) is a major
cerebrospinal fluid (CSF) protein produced by arachnoid cells, and its
concentration in the CSF is reportedly decreased in iNPH. L-PGDS acts as a
prostaglandin D2-producing enzyme and behaves as a chaperone to prevent the
neurotoxic aggregation of amyloid beta (Aβ) implicated in Alzheimer’s disease,
a major comorbidity of iNPH. The aim of this study was to confirm the L-PGDS
decrease in DESH-type iNPH and to clarify its relationship with
clinico-radiological features or other CSF biomarkers.

18. Representative magnetic resonance images of disproportionately
enlarged subarachnoid-space hydrocephalus (DESH, upper row) and
non-DESH ventriculomegaly (bottom row). Asterisks mark dilatation of
the Sylvian fissure. Arrow heads, tight high convexity; Bars,
callosal angles; Arrows, tight medial parietal sulci.

19. Methods
We evaluated of 22 patients (age: 76.4 ± 4.4 y; males: 10, females: 12)
referred for ventriculomegaly without CSF pathway obstruction, and conducted a
CSF tap test to determine the surgical indication. CSF concentrations of
L-PGDS, Aβ42, Aβ40, and total tau (t-tau) protein were determined using
enzyme-linked immunosorbent assays. Clinical symptoms were evaluated by the
iNPH grading scale, mini-mental state examination, frontal assessment battery
(FAB), and timed up and go test. The extent of DESH was approximated by the
callosal angle, and the severity of parenchymal damage was evaluated by the
age-related white matter change (ARWMC) score.

20. Results
L-PGDS and t-tau levels in CSF were significantly decreased in DESH patients
compared to non-DESH patients (p = 0.013 and p = 0.003, respectively). L-PGDS
and t-tau showed a significant positive correlation (Spearman r = 0.753,
p < 0.001). Among the clinico-radiological profiles, L-PGDS levels correlated
positively with age (Spearman r = 0.602, p = 0.004), callosal angle (Spearman
r = 0.592, p = 0.004), and ARWMC scores (Spearman r = 0.652, p = 0.001), but
were negatively correlated with FAB scores (Spearman r = 0.641, p = 0.004).

21. Comparisons of CSF biomarkers among the two ventriculomegalic groups (DESH-based or
tap-test-based) and control group. Central bars: median values, box edges: range of
75 percentile, whisker edges: upper and lower limit values. Significant
differences: *p < 0.05, **p < 0.01, and ***p < 0.001 by one-way analysis of variance
followed by post hoc Newman-Keuls multiple comparison tests. Aβ: amyloid beta DESH:
disproportionately enlarged subarachnoid-space hydrocephalus, L-PGDS:
lipocalin-type prostaglandin D synthase, t-tau: total tau.

22. Conclusions
Our data support the diagnostic value of L-PGDS as a CSF biomarker for iNPH
and suggest a possible interaction between L-PGDS and tau protein. In
addition, L-PGDS might work as a surrogate marker for DESH features, white
matter damage, and frontal lobe dysfunction.

23. Thanks for listening
References: Medscape 2017