Normal Pressure Hydrocephalus 23/11 2015 Erika Lindstrøm

Outline Characteristics of NPH Overview of Cerebrospinal fluid flow Stages of NPH Ventricle enlargement Diagnostics, W. Bradley Diagnostics, Rikshospitalet New findings Image source: Alz.com

Characteristics of NPH A form of dementia. First symptom is gait disturbance, followed by dementia and urinary incontinence. First described by Hakim and Adams and Adams et al. in 1965. Today, up to 10% of people suffering from dementia may have NPH. Can occur in people of any age, but most common in the elderly. To be diagnosed, enlarged ventricles and at least a portion of the clinical triad (gait disturbance, dementia, urinary continence) . Differs between idiopathic and secondary (may be caused by subarachnoid hemorrhage, head trauma, tumor etc.). Treatable by surgical CSF shunting.

Cerebrospinal fluid (CSF) CSF production 500 ml/day, mainly by the choroid plexus, recently suggested also that production occur in the brain parenchyma. Transportation: Bulk flow of CSF passes from lateral ventricles through the foramen of Monro into the third ventricle, through the aqueduct and fourth ventricle and out into the subarachnoid space via the foramina Lushka and Magendie. Image source: humanphysiology.academy

Stages of NPH Early stage of NPH display enlarged ventricles, and minimal, if any, atrophy. When the brain expands during systole in healthy elderly patients, it expands outward toward the subarachnoid space (SAS) and inward toward the ventricles. In patients with early NPH, the brain is already expanded outwards, so all systolic expansion is directed inward to the enlarged ventricles. This larger drumhead of the enlarged ventricles leads to hyperdynamic CSF flow through the Aqueduct. If these patients are not shunted, they will eventually develop atrophy and the amount of systolic expansion will be reduced. Thus, hyperdynamic CSF flow indicates that atrophy has not yet taken place. While the mean intraventricular pressure may be normal, the pulse pressure is often 6-8 times normal.

Ventricle enlargement Upper images A & B: Healthy person with normal ventricles Lower images C & D: NPH patient with dilated ventricles For NPH patients, the tissue surrounding ventricles may not be may not appear shrunken. Patients suffering from Alzheimer’s disease also have enlarged ventricles, caused by tissue shrinkage. Image source: neuropsychconsulting.wordpress.com

Diagnostics, William Bradley Bradley et al. suggested in Normal-Pressure Hydrocephalus: Evaluation with Cerebrospinal Fluid Flow Measurements at MR Imaging (1996) that the stroke volume of CSF recorded in the aqueduct could be used for diagnostic NPH. They reported that if the stroke volume were greater than 42 µL, the patients were considered to suffer from hyperdynamic CSF flow and should be treated by shunting. Their study involved 18 patients, where 12 patients had a stroke volume larger than the critical 42 µL and were treated successfully. The patients with stroke volume smaller than the critical displayed a success rate of 50%. In a review article CSF flow in the brain in the context of Normal Pressure Hydrocephalus (2015) Bradley adjusted the number and suggested that the critical value should be at least twice the value of normal stroke volume, found from a test group measured with the same MRI system. Patients in early stage may not have developed hyperdynamic CSF flow, and patients that already have developed atrophy will not display volumes twice the normal.

Diagnostics, Rikshospitalet Eide reported a study of 39 NPH patients in his article Intracranial pressure parameters in idiopathic normal pressure hydrocephalus treated with ventriculo-peritoneal shunts (2005) where he analyzed both mean and pulse pressure of the patients in terms of intracranial pressure measurements. Mean ICP: sum of pressure levels divided by the number of samples, fig. b: 7.6mmHg. Mean ICP wave amplitude: balanced positions of occurrences single wave amplitudes, fig b: 1.8mmHg. Mean ICP wave amplitudes were significantly higher in NPH patients improving clinically after shunt treatment, while no difference in mean ICP was documented. Pressure parameters were computed in time windows of 6 seconds.

MRI, NPH vs. healthy subjects MRI method is not associated with any risk while ICP method is a surgical method. Region of interest for aqueduct is narrow, usually 10-20 pixels. Comparison between 4 healthy subjects (20 measurements) and 23 NPH patients display that both pressure gradients, mean velocities and flow rates are in the same regime. Velocities were extracted just below the Foramen Magnum, region of interest typically 400-700 pixels. No correlation between intracranial pulse pressure amplitude and pressure gradients recorded at Foramen Magnum.

New findings One difference detected is bilateral flow, NPH patients display bilateral flow throughout the cycle.

New findings Subject Delta V Subject Delta V 2 0.263 4 0.286 9 0.092 10 0.177 11 0.148 12 0.102 14 0.342 16 0.257 17 0.198 18 0.071 19 0.076 20 0.131 22 0.113 23 0.216 25 0.215 28 29 0.044 41 0.024 46 0.020 47 -0.048 51 0.012 Subject Delta V ErikaPPU1T1 0.0446 ErikaPPU2T2 -0.0362 ErikaECGT1 -0.0314 ErikaPPU1T2 0.0374 -0.0322 KentPPU1T1 0.0319 KentPPU2T2 0.0437 KentECGT1 0.0210 KentPPU1T2 0.0118 0.0780 JacobPPU1T1 0.0646 JacobPPU2T2 0.3077 JacobECGT1 0.0160 JacobPPU1T2 0.1158 JacobPPU1T3 0.1288 VegardPPU1T1 0.1832 VegardPPU2T2 0.1810 VegardECGT1 0.0708 VegardPPU1T2 0.1886 0.1873 Measurements during one cycle display that a positive net flux is dominating. Mean value: 0.1049 ml

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