normal pressure hydrocephalus - cerebrospinal fluid shunt technology - complications
hidrocefalia de pressão normal - derivações liquóricas - complicações
Normal pressure hydrocephalus (NPH) is a neurological syndrome which manifests typically
between 60 and 80 years of age, characterized by a triad of symptoms consisting of
gait apraxia, dementia and urinary incontinence, associated with ventriculomegaly
(detected radiologically) and normal pressure of the cerebrospinal fluid (CSF)[1 ],[2 ],[3 ].
NPH can be divided into two categories: idiopathic and secondary. The secondary NPH
occurs in the context of neurological events such as subarachnoid hemorrhage (SAH),
intraventricular hemorrhage caused by trauma or aneurysm rupture and meningitis. In
contrast, idiopathic NPH usually occurs between the sixth and eighth decades of life
and does not have its pathophysiological mechanisms completely understood[4 ],[5 ],[6 ].
Once NPH is a rare case of reversible dementia, it is essential to have an adequate
clinical assessment, early diagnosis and proper treatment in such cases 4-7. Standard
treatment is accomplished through the implantation of a ventricular shunt, offering
the possibility of significant neurological improvement[7 ],[8 ],[9 ].
Different types of ventricular shunts are possible, but the most common is the ventricular
peritoneal shunt (VPS), performed by using a thin catheter whose interior flow is
unidirectional (craniocaudal) due to the presence of a device coupled to the valve
system, which communicates the cerebral ventricles with the peritoneal cavity, where
the excess CSF is drained[4 ],[5 ],[6 ],[7 ].
Complications related to VPS procedure are mainly biological and mechanical, and the
infection is still the most feared figure in the case of biological complications.
Among mechanical complications (such as proximal shunt obstruction, headache, dizziness,
slit ventricle syndrome, subdural or extradural hematomas, secondary paralysis of
cranial nerves and craniosynostosis), the most frequent and important are attributed
to changes related to the strength of drainage system, which results in excessive
CSF drainage. This phenomenon is called siphon effect[10 ],[11 ],[12 ],[13 ],[14 ].
In general, the siphon effect occurs due to the increased flow of CSF from the ventricles
drained after postural changes such as sit or stand up. This phenomenon is due to
the increased hydrostatic pressure (HP) and perfusion pressure (PP) of the drainage
system. However, there are reports in the literature that some physiological mechanisms,
such as increased intra-abdominal pressure (IAP ) and the reduction of intracranial
pressure (ICP) during postural changes has a preventive effect on the siphon effect[10 ],[11 ],[12 ],[13 ],[14 ],[15 ],[16 ].
Many of CSF drainage systems have been designed to prevent excessive drainage such
as adjustable valves, flow-regulated valves and gravitational antisiphon valves (the
latter two valves not only controlled by differential pressure, but also under the
influence of gravity as the position the body)[17 ],[18 ],[19 ],[20 ],[21 ],[22 ],[23 ].
This study aims to evaluate the performance of a valve with anti-siphon device (SPHERA®
- [Figure 1 ])[20 ] in the treatment of patients with NPH and compare it with the performance observed
in another group of patients with NPH who underwent the same procedure (VPS), but
whose valves had no anti-siphon mechanism.
Figure 1 SPHERA® Valve.
METHOD
The research project was approved by the ethics committee of Hospital das Clinicas,
Faculdade de Medicina da Universidade de São Paulo (CAPPESQ 10992).
Sample
Eighty nine patients with normal pressure hydrocephalus were selected and had their
medical profiles retrospectively analysed. Patients presented with clinical (dementia,
urinary incontinence, gait apraxia) and radiological (cranial tomography or magnetic
resonance imaging demonstrating ventriculomegaly; Evans index > 0.3). They were admitted
in the group of Cerebral Hydrodynamics, Division of Functional Neurosurgery, Institute
of Psychiatry, Hospital das Clinicas, Faculty of Medicine, University of São Paulo
(HC - USP), from September 2008 to July 2012, treated by ventriculoperitoneal shunt
(VPS).
Inclusion criteria were: age between 60 and 95 years old, clinical and radiological
diagnosis of normal pressure hydrocephalus and improvement after lumbar puncture (Tap
test).
Exclusion criteria were: presence of severe systemic diseases.
Procedures
Selection of patients
All patients were selected after clinical and radiological evaluation. The radiological
criterion used to evaluate ventricular size was the ratio of Evans, which is the ratio
between the maximum width of the anterior horn of the lateral ventricles and the maximum
width of the skull (internal board of the parietal bones). Hydrocephalus is defined
by an index greater than or equal to 0.3 index.
After confirming the diagnosis of normal pressure hydrocephalus, patients underwent
a Tap test, whose steps were as follows:
The patient was analyzed according to gait and cognitive pattern;
Then, a lumbar puncture was performed with removal of approximately 40-50 ml of cerebrospinal
fluid (CSF);
After about 180 minutes, the patient was again analyzed according to gait and cognitive
pattern.
From 89 patients initially selected, only 34 presented with improvement after Tap
test, being then included in the study. Four patients among the 34 presented with
severe systemic diseases, being then excluded from study. After all, 30 patients participated,
being consecutively divided in group 1 (anti-siphon) and group 2 (without anti-siphon),
both groups with 15 patients. Allocation was performed consecutively, without randomization.
Ventricular shunt
One group was selected for the implantation of fixed pressure (medium and low pressure)
with anti-siphon mechanism membrane (SPHERA®, HPBIO, São Paulo, Brazil) valve. SPHERA®
valve operates by a mechanism coupled with a coil spring and a ruby ball (ball and
spring mechanism). According to the characteristic of the spring, four levels of pressure
difference ensures a physiological flow of CSF: extra low (1 to 3 cm H2O) and low
(3 cm H2O -7), medium (7 to 11 cm H2O) and high (11 to 14 cm H2O). The body of the
prosthesis measures 42 x 14 x 6.5 mm. Its proximal portion contains the valve mechanism,
the central part is the digital camera for pumping and punch, and the distal part
contains the anti-siphon mechanism membrane. When the distal pressure becomes negative,
the membrane temporarily occludes the system, avoiding excessive drainage. This occurs
when the patient is in the standing position (up to - 50 cm H2O) or additionally during
inspiration in patients with ventriculopleural shunt (up to - 8 cm H2O).
The other group was subjected to similar procedures, but without anti-siphon mechanism
(PS Medical® valve, Medtronic).
The criterion for the choice of opening pressure of the implanted valves was the final
value of CSF pressure measured after completion of the Tap test. Low pressure valves
were implanted in patients who had values lower than 4 cm H2O, medium pressure in
patients with values between 5 and 10 cm H2O and high pressure in patients with values
greater than 10 cm H2O.
Postoperative follow-up
Patients were evaluated for a year after surgery, according to pre-established routine
outpatient visits: 10 days after surgery to removal of stitches, three months, six
months and one year after surgery. Follow-up criteria were:
Clinical: comparison of pre and post neurological surgery, presence of signs and symptoms
of malfunction or excessive drainage system (headache, positional headaches, nausea,
vomiting, visual changes, altered level of consciousness);
Radiological: pre and postoperative CT, immediately after surgery and after three
months. Signs of CSF hypodrainage (Evans index > 0.3) and signs of CSF overdrainage
(subdural collections > 1 cm) were evaluated.
Scales
The following scales were used for clinical and radiological assessment of the patients:
1) Mini Mental State Examination (MMSE)[21 ],[22 ]
Objective: To evaluate cognitive changes.
Score: 0 to 30 (higher is better).
2) Japanese NPH Scale (NPH Scale)[23 ] – [Figure 2 ]
Figure 2 Japanese scale for NPH.
Objective: scoring patients according to clinical characteristics of NPH triad.
Score: 0 to 12 (higher is worse).
Statistics
According to the nature of the variables the data were analyzed by the absolute and
relative frequency and applied the following tests: Kolmogorov-Smirnov test, t-test,
Mann-Whitney and Wilcoxon. The value of 5% (p < 0.05) was adopted as the threshold
for rejecting the null hypothesis with a confidence interval of 95%.
RESULTS
Anthropometric data
Of the 30 patients, there were 23 men and 7 women. In group 1 (SPHERA®), age ranged
from 60 to 85 years (mean 71 years) and Body Mass Index (BMI) ranged from 18 to 30
kg/m2 (mean 24.8 kg/m2 ). In group 2 (PS Medical®), age ranged between 60-79 years
(mean 70 years) and BMI ranged from 21 to 36.8 kg/m2 (mean 26 kg/m2 ). There was no
statistical difference between the mean age and BMI between groups.
Twenty-five patients had complete clinical triad, 2 patients had gait apraxia and
urinary incontinence, 2 patients had gait apraxia and dementia and 1 patient had only
dementia. All patients had communicating hydrocephalus according to CT and MRI, and
Evans index ranged from 30% to 49% (mean 39.8%).
[Table 1 ] shows the scores obtained by using the Japanese scale for NPH while performing Tap-
test, after 3 months and 12 months after surgery.
Table 1
Normal pressure hydrocephalus (NPH) Japanese scale during Tap test and follow-up.
Group
Best before Tap test
Best after Tap test
After 3 months
After 12 months
Group 1 – anti-siphon (n = 15)
NPH scale
8 (5-12)
7 (2-12)
8 (4-12)
6 (1-12)
Group 2 – without anti-siphon (n = 15)
NPH scale
6 (2-11)
5 (2-8)
4 (0-10)
6 (0-12)
Group 1 (SPHERA® valve)
Of the 15 patients who constituted group 1, 12 were men and 3 were women. Medium pressure
valves were implanted in 10 patients and low pressure valves (SPHERA®, HPBIO) in 5
patients.
Clinical evaluation
After one year of follow up, 10 patients had clinical improvement (10/15 = 66%), 2
patients (2/15 = 13%) remained unchanged compared to the preoperative period and 3
patients (3/15 = 20%) showed clinical worsening after one year of monitoring. During
cognitive assessment by MMSE, the best results (mean and variation) before and after
the Tap test, after 3 months and after 1 year were 14 (8-22), 14 (2-23), 14 (3-26)
and 15 (9-27), respectively.
Radiological evaluation
Eleven patients showed no signs of parenchymal bleeding or subdural collections after
one year of surgery ([Figure 3 ]). Two patients presented 45 days and 6 months after surgery subdural chronic hematomas
in the right cerebral hemisphere, both in the right frontoparietal region. In the
first case, there was 2 cm in the greatest thickness. In the second case, it was observed
thickness of 1.5 cm and minimum deviation from the midline to the left. In both cases
there was need for surgical drainage without changing valves.
Figure 3 Pre and post operative images of a typical normal pressure hydrocephalus patient of
group 1.
[Table 2 ] shows the radiographic patterns presented by patients in group 1.
Table 2
Radiological evaluation in group 1.
< 3 ms
3 months
6 months
9 months
12 months
Subdural hematomas > 1 cm
1
-
1
-
-
Subdural hematomas < 1 cm
-
-
-
-
-
Ventricular enlargement
-
-
-
1
-
Hemoventricle
-
-
1
-
-
Slit ventricle
-
-
-
-
-
Group 2 (PS Medical® valve)
Of the 15 patients who constituted group 2, 11 were men and 4 were women. 12 medium
pressure valves and 3 low pressure valves (PS Medical®, Medtronic) were implanted.
Clinical evaluation
After one year of follow-up, 8 patients (8/15 = 53%) showed clinical improvement,
2 patients (2/15 = 13%) remained unchanged compared to the preoperative period and
5 patients (5/ 15 = 33%) showed clinical worsening after a year of monitoring.
During cognitive assessment by MMSE, the best results (mean and variation) before
and after the Tap test, after 3 months and after 1 year were 22 (13-29), 20 (1-30),
16 (2-29) and 21 (10-30), respectively.
Radiological evaluation
Five patients had chronic subdural hematoma > 1 cm during follow-up ([Figure 4 ]). One in the first month (frontoparietal region, measuring 2.1 cm; two after two
months (both right frontoparietal region without midline deviation or ventricular
compression, one measuring 1.2 cm, and the other measuring 1.4 cm); one after three
months (in the right frontal parietal region measuring 1.1 cm without midline deviation
or ventricular compression) and one six months after surgery (bilateral frontoparietal
region, measuring 1.2 cm).
Figure 4 Pre and post operative images of a subject of group 2 who developed subdural hematoma
after ventricular peritoneal shunt.
Four of the five largest hematomas that occurred in the first six months required
reoperations for hematoma evacuation and replace valves for high-pressure valves (three
cases after 2 months of surgery) and closure of the shunt system by occlusion of catheter
(one patient 3 months after surgery). The remaining case was approached conservatively.
One patient had slit ventricles syndrome after six months of surgery without midline
deviation or ventricular compression ([Figure 5 ]). We opted for a conservative approach.
Figure 5 Pre and post operative images of a subject of group 2 who developed slit ventricle
syndrome after ventricular peritoneal shunt.
[Table 3 ] presents the radiographic patterns presented by patients in group 2.
Table 3
Radiological evaluation in group 2.
< 3 ms
3 months
6 months
9 months
12 months
Subdural hematomas > 1 cm
2
2
1
Subdural hematomas < 1 cm
-
-
2
-
-
Ventricular enlargement
-
2
1
-
Hemoventricle
-
-
-
-
Slit ventricle
-
-
1
-
-
Comparison between groups
In both groups, there was clinical improvement after one year (p = 0.005) and that
was superior in Group 1, however without statistical significance (p = 0.059). NPH
scale after one year revealed statistical significant difference in both groups (p
= 0.005), while Evans index did not differ in both groups (p = 0.105).
Overdrainage complications were significantly lower in Group 1 (p = 0.042). The need
for reoperation in the first year after surgery in both groups is presented in [Table 4 ]. There was a smaller number of reoperations in Group 1, not statistically significant
(p > 0.05).
Table 4
Reoperation after 1 year.
3 ms
6 months
9 months
12 months
Group 1
1
-
1
-
Group 2
4
-
-
-
[Table 5 ] presents the causes of emergency room care in the HCFMUSP during the first year
after surgery of patients in groups 1 and 2. There were fewer clinical complications
in group 1 (p = 0.05).
Table 5
Reasons for emergencial medical evaluation during the first year after surgery in
groups 1 and 2.
Symptoms/Signs
Group 1 (n = 15)
Group 2 (n = 15)
Headache
2
4
Impairment of level of consciousness
1
5
Dizziness
1
3
Falls
1
2
Behavior changes
2
3
Vomiting
1
2
DISCUSSION
Normal pressure hydrocephalus is one of the few causes of dementia with potential
for reversal of symptoms. Hakim and Adams in 1965 described the classic triad that
can characterize disease in varying degrees of combination[1 ],[2 ],[3 ].
A ventriculoperitoneal shunt is the procedure of choice for the treatment of NPH.
Approximately 50-70% of patients report improvement after shunt. However, complications
related to the procedure are still frequent and often severe, ranging from 13 to 40%
of patients in the main series. The siphon effect, which occurs due to the increased
flow of CSF from the ventricles drained after postural changes, like sit or stand,
is being increasingly investigated in order to reduce complications[4 ],[5 ],[6 ],[7 ],[8 ],[9 ],[10 ].
Many CSF drainage systems have been designed to prevent excessive drainage such as
adjustable valves, flow-regulated valves, and gravitational anti-siphon valves[24 ],[25 ].
Several studies are known in this regard. The Codman Medos valve, for example, allows
adjustment of the pressure in 18 levels between 30 and 200 mm H2O. A series of 90
patients was published with satisfactory clinical results. Another retrospective study
was published in 583 patients with hydrocephalus due to various causes who were treated
with the Codman Hakim programmable valve. The proGAV valve (Aesculap) also has support
in the literature[26 ],[27 ].
The use of Strata® valve has been described previously, with a success rate of approximately
80% and 20% of complications[28 ],[29 ],[30 ]. Orbis Sigma® is a self-regulating valve and constant flow valve. Despite being
probably one tool applicable in cases of NPH, the literature lacks studies corroborating
results in these patients[31 ].
Once complications related to CSF overdrainage are frequent and may be severe, the
present study evaluated the performance of a valve with anti-siphon device (SPHERA®)
in the treatment of patients with NPH compared to the performance observed in another
group of patients with NPH who underwent the same procedure, but whose valves had
no anti-siphon mechanism (PS Medical®, Medtronic).
We evaluated 30 patients with NPH separated into 2 groups according to the type of
valve used. We studied the clinical and radiological outcome, complications, reoperations,
and symptomatology after a 1 year follow up. In group 1 (Anti-siphon), the improvement
rate was 66 %, with 5 radiological complications and reoperation in 2 patients. In
group 2 (without Anti-siphon), there was improvement in 53% of patients, with 11 complications
and reoperation in 3 patients.
In both groups, there was clinical improvement after one year (p = 0.005) and that
was superior in group 1, however without statistical significance (p = 0.059). Overdrainage
complications were significantly lower in group 1 (p = 0.042). There was a smaller
number of reoperations in group 1, not statistically significant (p > 0.05). Thus,
SPHERA® valve was similar to the fixed pressure valve PS Medical® regarding clinical
treatment and was superior in the management of overdrainage complications.
The use of valves with different pressures between the two groups (low and medium)
were statistically significant (p = 0.025). Then a regression analysis was performed
by controlling this variable. With this control, the variable “had complication” was
significantly different between groups (p = 0.049).
As there were more patients in group 2 with medium pressure valves than in group 1,
it was expected that the first presented with lower rates of overdrainage. However,
in reality, a larger number of overdrainage complications happened in group 2, reinforcing
the role of Anti-siphon device of SPHERA® valve in preventing such complications.
Some limitations should be considered. First, our analysis was a retrospective study
without randomization in group allocation. The best study design to test hypothesis
should be prospective and randomized. This methodological weakness surely brings bias
which may interfere with inferences from study.
Additionally, when the patient is elderly, one should be cautious with the results
of improvement of dementia after shunt. The association with Alzheimer’s disease and
other dementia is known, sometimes without any improvement after shunt[32 ].
Then, we did not use any objective functional scale to assess patients, such as the
modified Rankin Scale and Barthel Index. Additionally, screening for shunt surgery
was based on the results of Tap test. It was the only preoperative test used for the
treatment of patients due to its applicability, validity and availability, as well
as patient comfort, because hospitalization was not required during the protocol.
Although with lower sensitivity (26-61%) compared to the infusion test (57-100%) and
external lumbar drainage (50-100%), Tap test is feasible and its only great weakness
is the potential loss of candidates for surgery[30 ].
Another important point is that the gold standard treatment for NPH is currently done
with programmable valves[9 ],[20 ]. Thus, comparison of SPHERA® valve with a type of fixed pressure valve (PS Medical®)
may decrease, but not invalidate the superiority of SPHERA® valve. Future trials comparing
the latter with programmable valves will be needed to clarify these questions.
A linear relationship between shunt valve type and incidence of subdural hematoma
remains unclear. Although there is limited evidence data generally assuming that subdural
hematoma formation may occur as a consequence of excessive or too rapid CSF drainage,
the use of flow-limiting valves or antisiphon devices to reduce the incidence of subdural
hematomas has yet to be clearly proved.
We must highlight that SPHERA® valves applied in the study were donated by HPBio company.
Finally, our results are tied to a 1-year follow-up. Although encouraging, they are
still initial and further follow up must be documented.
In conclusion, SPHERA® valve showed satisfactory results, since the clinical improvement
was observed in 66% of patients and complications were significantly less common because
of Anti-siphon device.
Certainly, further studies are needed. However, SPHERA® valve is a safe and applicable
tool in the treatment of NPH.
