Prevalence of Possible Idiopathic Normal Pressure Hydrocephalus in Sweden: A Population-Based MRI Study in 791 70-Year-Old Participants

BACKGROUND AND OBJECTIVES: Very divergent prevalence rates for idiopathic normal pressure hydrocephalus (iNPH) are reported, probably due to differences in study sample selection and diagnostic criteria. This MRI-based study aimed to determine the prevalence of iNPH and iNPH-specific radiologic changes and their association with clinical symptoms in a large, 70-year-old population-based cohort (Gothenburg H70). METHODS: In this cross-sectional study, disturbances in gait and balance, cognition, and urinary continence were assessed using clinical examination and self-report. MRI was evaluated for iNPH-specific imaging markers. iNPH was diagnosed according to International Guidelines (I.G.). Based on radiologic findings, participants were allocated to 1 of 4 groups: (A) Evans index (EI) ≤0.3 (reference), (B) EI >0.3 without other iNPH-typical radiologic findings, (C) radiologically probable iNPH according to I.G., and (D) radiologically holistically probable (h-probable) iNPH fulfilling radiologic criteria according to I.G. plus highly iNPH-specific changes according to an experienced neuroradiologist. RESULTS: The Gothenburg H70 Studies include 791 individuals (377 men, 414 women) born in 1944 who underwent brain MRI. The prevalence of iNPH was 1.5% (2.1% for men, 0.96% for women) according to I.G. Ninety participants (11%) had EI >0.3 without other iNPH-typical radiologic findings, 29 (3.7%) fulfilled the I.G. radiologic probable iNPH criteria alone, and 11 (1.4%) were classified as radiologically h-probable iNPH. Forty participants (5.1%) had I.G. radiologic features of iNPH (70% men vs 30% women, p = 0.005). Gait disturbances were more common in participants with EI >0.3 without other radiologic iNPH features (B) (33%) compared with the reference group (A) (19%) (p = 0.006). All clinical symptoms were more common in participants with I.G. radiologic features of iNPH (C + D) than they were in the reference group (A) (p < 0.03). DISCUSSION: The iNPH prevalence of 1.5% among 70-year-olds, which is considerably higher than earlier reported in this age group, suggests that iNPH may be more common than previously assumed. This is supported by the 5.1% total prevalence of imaging signs of iNPH. Ventriculomegaly without other iNPH-typical radiologic findings may be an early sign of developing iNPH in some patients.

Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus: A Tensor Imaging Study.

Idiopathic normal pressure hydrocephalus (iNPH) is a disorder with unclear pathophysiology. The diagnosis of iNPH is challenging due to its radiological similarity with other neurodegenerative diseases and ischemic subcortical white matter changes. By using Diffusion Tensor Imaging (DTI) we explored differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in iNPH patients (before and after a shunt surgery) and healthy individuals (HI) and we correlated the clinical results with DTI parameters. Thirteen consecutive iNPH-patients underwent a pre- and post-operative clinical work-up: 10 m walk time (w10mt) steps (w10ms), TUG-time (TUGt) and steps (TUGs); for cognitive function MMSE. Nine HI were included. DTI was performed before and 3 months after surgery, HI underwent DTI once. DTI differences analyzed by manually placing 12 regions-of-interest. In patients motor and balance function improved significantly after surgery (p = 0.01, p = 0.025). Higher nearly significant FA values found in the patients vs HI pre-operatively in the thalamus (p = 0.07) accompanied by an almost significant lower ADC (p = 0.08). Significantly FA and ADC-values were found between patients and HI in FWM (p = 0.02, p = 0.001) and almost significant (p = 0.057) pre- vs postoperatively. Postoperatively we found a trend towards the HIs FA values and a strong significant negative correlation between FA changes vs. gait results in the FWM (r = -0.7, p = 0.008). Our study gives a clear indication of an ongoing pathological process in the periventricular white matter, especially in the thalamus and in the frontal white matter supporting the hypothesis of a shunt reversible thalamo-cortical circuit dysfunction in iNPH.

Ventricular volumetry and free-water corrected diffusion tensor imaging of the anterior thalamic radiation in idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) has not been completely clarified. We investigated the brain structure in iNPH using automatic ventricular volumetry, single-tensor diffusion tensor imaging (DTI) and bi-tensor free-water (FW) imaging analyses while focusing on cognitive impairments before and after lumboperitoneal shunt surgery. MATERIALS AND METHODS: This retrospective study included 12 iNPH patients with structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) on a 3T-MRI scanner who underwent neuropsychological assessments before and after shunting and 8 healthy controls. Ventricular volumetry was conducted on structural MRI datasets using FreeSurfer. Ventricular volume was compared pre- and postoperatively. Correlation analyses were performed between ventricular volume or volume change and neuropsychological scores or score change. Tract-based spatial statistics were performed using dMRI datasets for group analyses between iNPH and controls and between pre- and post-surgery iNPH patients and for correlation analyses using neuropsychological scores. Tract-specific analyses were performed in the anterior thalamic radiation (ATR), followed by comparison and correlation analyses. RESULTS: The third ventricular volume was significantly decreased after shunting; its volume reduction negatively correlated with a neuropsychological improvement. Compared with controls, iNPH patients had lower fractional anisotropy and higher axial, radial, and mean diffusivities, and FW in the periventricular white matter including ATR, resulting in no difference in FW-corrected indices. Single-tensor DTI indices partially correlated with neuropsychological improvements, while FW-corrected indices had no correlations. CONCLUSION: Third ventricle enlargement is possibly linked to cognitive impairment and FW imaging possibly provides better white matter characterization in iNPH.

Surgical Indications and Operative Results of Lumbosubarachnoid-Lumboepidural Shunting in 29 Patients with Idiopathic Normal Pressure Hydrocephalus under Local Anesthesia.

This study consisted of 29 patients with idiopathic normal pressure hydrocephalus (iNPH) who underwent lumbosubarachnoid-lumboepidural (L-L) shunting under local anesthesia in accordance with our surgical indications of L-L shunting. (1) CSF absorption within the lumbar epidural space and shunt clearance were confirmed in all patients after operation. (2) Shunt responders (R) were 25 of 29 cases (86.2%) 3 months after surgery. Among the R, symptom exacerbation was confirmed in three patients (12%) within the follow-up period (mean, 25.1 months). In each of these patients, shunt function were maintained and remained unchanged even with pressure resetting, the cause being an intracranial/extracranial disease other than iNPH. (3) The initial pressure setting for this method was 8 cmH2O, with gradual change to higher pressures, such that the setting for Patient 11 and thereafter became 20 cmH2O. (4) As postsurgical complications, subcutaneous cerebral spinal fluid collection (SCC) was confirmed in five patients (17.2%). In high-pressure resetting and follow-up observation, SCC was not observed in all patients. Epidural catheter displacement was confirmed in three patients (10.3%). No recurrence was noted after the secure fixation of the catheter at the fascia insertion portion and 2 days' postsurgical bed rest. Hence, L-L shunting is an effective shunt therapy for iNPH.

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. METHODS: Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. RESULTS: Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. CONCLUSIONS: Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

A combined cognitive and gait quantification to identify normal pressure hydrocephalus from its mimics: The Geneva's protocol.

OBJECTIVES: Idiopathic normal pressure hydrocephalus (iNPH) is very prevalent in aging, underdiagnosed, and represents a rare cause of reversible neurological condition. The clinical triad of iNPH - gait, cognitive and urinary symptoms - and its neuroradiological features (i.e. ventriculomegaly) are not specific and found a various neurodegenerative and/or vascular conditions. We present our iNPH standardized protocol at the Geneva University Hospitals involving a multispecialty team of behavioral neurologists, neurosurgeons, neuropsychologists, engineers, and physical therapists. Based on a pragmatic approach, the goal of this protocol is to improve the identification of older patients with iNPH from its mimics (i.e. vascular dementia or other parkinsonian syndromes). PATIENTS AND METHODS: We used a novel standardized paradigm with a simultaneous quantification of cognition and gait (dual task gait assessment and mental imagery of locomotion) before and 24h after CSF tapping. RESULTS: We assessed 125 patients with suspicion of iNPH (age: 75.9±7.4years; 34.4% female) in 5 years: 54.4% of probable/possible iNPH and 45.6% of mimics. Among the mimics, vascular dementia (24.6%) and patients with multifactorial conditions (19.9%) were the two most common diagnoses. A total of 27 patients with iNPH (39.7%) accepted the neurosurgical shunt procedure. CONCLUSION: This report shows that a quantified gait and cognitive assessment - using dual-task paradigms - before and after CSF tapping is feasible among older adults with suspicion of iNPH and that this multidisciplinary approach contributes to the identification of patients with iNPH from its mimics.

Serial positron emission tomography findings in a patient with hydrocephalic dementia and Alzheimer's disease.

Comorbidity of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) is not uncommon. However, few studies have reported the clinical courses of these patients in depth. A 73-year-old woman was confirmed to have AD by a biopsy performed during a shunt operation for NPH after a head trauma. She was followed for 4 years using serial neuropsychological tests and positron emission tomography (PET). Her clinical symptoms remained improved for 2.5 years and then declined. The 1-year minus the presurgical PET scan highlighted the bilateral frontal area, basal ganglia, and thalamus, which may reflect brain regions associated with the improvement of hydrocephalic dementia. On the other hand, the 1-year minus the 4-year scan highlighted the bilateral temporoparietal area and the posterior cingulate gyrus, which may reflect brain regions associated with the aggravation of AD. This subtraction method may be useful for monitoring the clinical course in patients with NPH and AD.

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.

Significance of periventricular hemodynamics in normal pressure hydrocephalus.

To delineate the pathophysiology of periventricular hemodynamics in normal pressure hydrocephalus, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) by using xenon-enhanced computed tomographic scans. Measurements were made on 7 patients in whom normal pressure hydrocephalus after subarachnoid hemorrhage had been confirmed by clinical improvement after shunting. We compared mean CBF values in the white matter and cortex of the frontal, temporal, parietal, and occipital lobes and in the thalamus before and after shunting, with an evaluation of dementia and the extent of ventricular dilation and periventricular lucency on computed tomographic scans. CBF returned to within normal limits in the white matter of the frontal and temporoparieto-occipital lobes. CBF restoration closely correlated with clinical improvement and reduction in ventricular dilation and periventricular lucency. We speculate that ischemia occurs initially in the periventricular white matter as a result of diffused cerebrospinal fluid and then extends of the cortex and to the thalamus, causing a "misery perfusion" state with neuronal dysfunction. Incomplete improvement of dementia and CBF in the cortex and thalamus may be explained by preexisting arteriosclerosis in aged patients, coexisting brain damage caused by subarachnoid hemorrhage and subsequent surgical insult in aneurysm patients, and delayed recovery of cortical function that has been secondarily impaired by the periventricular lesions.

Investigation of normal pressure hydrocephalus by 123I-IMP SPECT.

We evaluated N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) as a method for identifying normal pressure hydrocephalic (NPH) patients eligible for shunting procedures. 123I-IMP SPECT scans were taken before and after cerebrospinal fluid (CSF) taps in NPH cases. Post-subarachnoid hemorrhagic (SAH) patients showed apparent frontal blood flow reduction but non-SAH cases did not. The frontal blood flow increased in comparison with the temporal flow after CSF tapping in SAH cases who benefited most from shunting. Cerebral blood flow study before and after CSF removal is a potential method for classifying NPH patients likely to benefit from the shunting operation.

Comparison of ventricular enlargement and radiopharmaceutical retention: a cisternographic-pneumoencephalographic comparison.

The cisternograms and pneumoencephalograms of 58 patients with suspected "normal pressure" hydrocephalus were correlated and the relationship of ventricular radiopharmaceutical entry and stasis to ventricular size was analyzed. It was found that radiopharmaceutical entry relates directly to ventricular size, stasis occurring only in markedly enlarged ventricles. Cerebrospinal fluid imaging alone is a highly reliable diagnostic study only if patients exhibit the characteristic cisternographic patterns of normal pressure hydrocephalus. In those who do not, pneumoencephalography and cisternography are valuable complementary studies which can also be used to identify primary cortical atrophy.