Adjustable Gravitational vs. Adjustable Differential Pressure Valves in iNPH
Adjustable Gravitational vs. Adjustable Differential Pressure Valves in iNPH
The goal of the study is to verify theoretical benefit of ventriculoperitoneal shunting with
 MIETHKE M.blue® valve in patients with iNPH. The study is designed to assess walking and
 balance, urinary function, cognitive performance and quality of life before and after
 shunting and compare the results between the patients with MIETHKE M.blue® and MIETHKE proGAV
 2.0® (with SA 2.0®) valves.
Patients who will be referred to Military University Hospital Prague with suspicion of normal
 pressure hydrocephalus will be tested by conventional methods to consider implantation of a
 ventriculo-peritoneal shunt. This testing is performed during hospitalization and includes
 clinical examination of the patient by a neurosurgeon, neurologist and neuropsychologist
 including neuropsychological questionnaires or tests - MoCA, AVLT, ROCFT, TMT A + B, Phonemic
 Verbal Fluency Test (N, K, P), Semantic Fluence Test (animals, vegetables), subtest of
 battery WAIS III and GDS. Clinical examinations are followed by magnetic resonance imaging.
 Functional testing of cerebrospinal fluid circulation is initiated on the second day unless
 another cause of the patient's symptoms (AD, Parkinson's disease, vascular dementia, tumor,
 obstructive type of hydrocephalus - eg aqueductal stenosis, Blake's pouch cyst etc.) is
 present. The functional testing will involve lumbar infusion test and subsequent external
 lumbar drainage (ELD) for 120h, including biochemical analysis of CSF during the ELD. After
 this time, the objective improvement of the patient's gait with the aid of the Dutch Gait
 Scale will be evaluated with respect to the subjective evaluation by the patient or family
 (changes in urinary incontinence / urgency, headaches, etc.). If the diagnosis of
 normotensive hydrocephalus is confirmed, the patient will be indicated for a VP shunt
 implantation, which is used for permanent derivation of cerebrospinal fluid into the
 peritoneal cavity. As a result of cerebrospinal fluid derivation, the clinical condition of
 most of the patients improves. The operation process described by Michael J. Fritsch (Fritsch
 et al. 2014) will be modified for various valve types in accordance with the manufacturer's
 recommendations and assumed conditions for proper valve adjustment. Patients will be randomly
 implanted with a M.blue® or proGAV 2.0® (with SA 2.0®) valve (Christoph Miethke GmbH & Co.
 KG) in a randomized manner to form two study groups. The efficacy and safety of the proGAV
 2.0® (with SA 2.0®) valve has already been confirmed in a randomized prospective study in
 patients with idiopathic normotensive hydrocephalus (Lemcke et al. 2013). The theoretical
 benefit of the M.blue® valve lies in the targeted modification of the cerebrospinal fluid
 diversion during the active time of a day, when the opening pressure of the valve's
 gravitational unit is controlled according to the angle between the valve and the horizontal
 line. The basal opening pressure of the valve that has to be overcome in the supine position
 is controlled with a fixed differential pressure unit. ProGAV 2.0® is an adjustable
 differential pressure valve implanted with a shunt-assistant SA 2.0®. The shunt-assistant
 represents a fixed gravity unit that increases the pressure in the standing position, which
 must be overcome for the cerebrospinal fluid flow through th shunt. The opening pressure of
 the valve could be selected according to the patient's height and sex. The basal opening
 pressure of the valve that must be overcome in the supine position is controlled with an
 adjustable differential pressure unit that can be adjusted before and after the shunt
 implantation. In both valves, the opening pressure is the sum of the opening pressures of the
 gravitational and differential pressure units. The theoretical benefit of the M.blue® valve
 is the possibility of changing the opening pressure of the gravitational unit regulated
 according to the position of the head in the space and thus aiming more at the pressure
 conditions when the valve is not parallel to the horizontal line.

 Patients will not be familiar with the type of valve implanted with respect to subjective
 evaluation of patients during the follow-up. Initial valve settings will be in accordance
 with the manufacturer's recommendations. Follow-up of the patients will be guided in the
 usual regime according to the natural history of the disease: at one month of follow-up an
 outpatient clinical examination by a neurosurgeon, including brain CT scan; at three-months
 of follow-up an evaluation during a two-day hospitalization including collection of the
 following questionnaires, brain MRI, clinical examination by a neurosurgeon, neurologist and
 neuropsychologist and collection of cerebrospinal fluid from the pre-chamber for the
 biochemical analysis; at six-months an outpatient examination by a neurosurgeon; at one year
 of follow-up an evaluation during a two-day hospitalization including collection of the
 following questionnaires, brain MRI, clinical examination by a neurosurgeon, neurologist and
 neuropsychologist and collection of cerebrospinal fluid from the pre-chamber valve for
 biochemical analysis; at two-years of follow-up an outpatient clinical examination by
 neurosurgeon and neuropsychologist including brain CT scan including collection of the
 following questionnaires and collection of the cerebrospinal fluid from the pre-chamber of
 the valve for biochemical analysis.

 For the purpose of the study, the Dutch Gait scale (gait), UI-SF (incontinence) and MoCA
 (dementia) will be used to assess the outcome of the shunt operation to monitor the severity
 and nature of the main symptoms during the follow-up in pre-implant, three months, one year
 and after two years. The SF-12V2 will be used in a similar mode to monitor the quality of
 life of the patients. Severity of the symptoms will also be assessed by the Kiefer Scale,
 which was developed directly to monitor patients with idiopathic normotensive hydrocephalus.
 Charlson comorbidity index will be used to monitor covariates. All clinical examinations by a
 neurosurgeon will monitor early and late complications of the short-circuit operation
 (infection, hemorrhage, overdrainage, underdrainage, shunt malfunction), the number of valve
 setting changes and their range, unscheduled checks and shunt revisions and other unexpected
 events.

 The expected number of patients who will undergo all examinations after an annual check is 40
 (20 and 20).

 The expected benefit of the study is in particular to confirm the theoretical assumptions of
 an adjustable gravitational valve in patients with idiopathic normal pressure hydrocephalus
 and thus in improvement of the quality and life expectancy of these patients.
Inclusion Criteria:

 -  Age of patients (between 60 and 85 years old)

 -  Clinically suspected Normal Pressure Hydrocephalus (NPH) with at least gait and one
 other symptom from Hakim-Adams triad (incontinence or dementia)

 -  maximal initial pressure of 20 cmH2O during lumbar infusion test

 -  Rout during LIT >9mmHg/ml*min

 -  at least 15% improvement in Gait scale score after ELD

 -  Conclusion of neuropsychological examination suggestive of iNPH (based on MoCA, Test
 of phonemic and verbal fluency, RAVLT, ROCFT, TMT A and B, Subtest of WAIS III, GDS)

 Exclusion Criteria:

 -  Aetiology of hydrocephalus other than idiopathic normal pressure hydrocephalus
 (secondary normal pressure hydrocephalus - history of meningitis or subarachnoid
 haemorrhage, obstructive type of hydrocephalus - eg aqueductal stenosis, Blake's pouch
 cyst)

 -  Intracranial tumor

 -  Other neurodegenerative diseases may be present (AD, Parkinson's disease, Lewy body
 dementia, Progressive supranuclear palsy and cerebrovascular diseases), however have
 to be mild and evaluated in neurological, neuropsychological examinations and on MRI