The Kuopio idiopathic normal pressure hydrocephalus protocol: initial outcome of 175 patients.

BACKGROUND: The Kuopio University Hospital (KUH) idiopathic normal pressure hydrocephalus (iNPH) cerebrospinal fluid (CSF) shunting protocol is described together with the initial outcomes of 175 patients with probable iNPH treated according to this protocol from a defined population. Our secondary aim was to display the variety of differential diagnoses referred to the KUH iNPH outpatient clinic from 2010 until 2017. METHODS: Patients were divided into four groups according to the prognostic tests: tap test (positive or negative) and infusion test (positive or negative). The short-term outcome was compared between groups. The 3-month outcome following shunt surgery was assessed by measuring gait speed improvement, using a 12-point iNPH grading scale (iNPHGS) and the 15D instrument. RESULTS: From 341 patients suspected of iNPH, 88 patients were excluded from further research mostly due to deviation from the protocol's gait assessment guidelines. Hence 253 patients with suspected iNPH were included in the study, 177/253 (70%) of whom were treated with a CSF shunt. A favorable clinical outcome following surgery was observed in 79-93% of patients depending on the prognostic group. A moderate association (Cramer's V = 0.32) was found between the gait speed improvement rate and the prognostic group (X2, p = 0.003). Patients with a positive tap test had the highest gait speed improvement rate (75%). In addition, an improvement in walking speed was observed in 4/11 patients who had both a negative tap test and a negative infusion test. Other outcome measures did not differ between the prognostic groups. Conditions other than iNPH were found in 25% of the patients referred to iNPH outpatient clinic, with the most prevalent being Alzheimer's disease. CONCLUSIONS: Our results emphasize the importance of a systematic diagnostic and prognostic workup especially in cases with an atypical presentation of iNPH. Additional diagnostic testing may be required, but should not delay adequate care. Active surgical treatment is recommended in patients with a high clinical probability of iNPH. Other neurological conditions contributed to most of the non iNPH diagnoses.

Health-related quality-of-life outcome in patients with idiopathic normal-pressure hydrocephalus - a 1-year follow-up study.

BACKGROUND AND PURPOSE: This prospective study explored the factors affecting the health-related quality-of-life (HRQoL) outcome in patients with idiopathic normal-pressure hydrocephalus (iNPH) 1 year after the installation of the cerebrospinal fluid shunt. METHODS: The HRQoL outcome was evaluated using a 15D instrument, in which the minimum clinically significant change/difference has been estimated to be ±0.015. The follow-up data (15D, Mini-Mental State Examination, Beck Depression Inventory, iNPH Grading Scale), frontal cortical biopsy, Charlson Age Comorbidity Index and body mass index of 145 patients diagnosed with iNPH by clinical and radiological examination were analyzed. RESULTS: At 1-year follow-up, 63 (43%) patients had experienced a clinically significant improvement in HRQoL. Multivariate binary logistic regression analysis indicated that the absence of amyloid-ß and hyperphosphorylated tau pathology in the frontal cortical biopsy (53% vs. 33%; absolute risk difference, 20%; adjusted odds ratio, 2.27; 95% confidence interval, 1.07-4.84; P < 0.05) and lower body mass index (adjusted odds ratio, 0.90, 95% confidence interval, 0.82-0.98; P < 0.05) predicted favorable HRQoL outcome 1 year after the shunting. CONCLUSIONS: Less than half of the patients with iNPH experienced clinically significant favorable HRQoL outcome, partly explained by the patient's characteristics and comorbidities. The HRQoL approach reveals aspects that are important for the patient's well-being, but may also improve the quality of the outcome assessment of cerebrospinal fluid shunting. Study results may help clinicians to estimate which patients will benefit shunt surgery.

Health-related quality of life in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Factors affecting health-related quality of life (HRQoL) were explored in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Using the 15D instrument HRQoL was evaluated in 132 patients diagnosed with iNPH by clinical and neuroradiological examinations. The severity of iNPH symptoms was measured with the iNPH grading scale (iNPHGS), depressive symptoms with the Beck Depression Inventory (BDI-21) and cognitive impairment with the Mini-Mental State Examination. RESULTS: The mean (SD) 15D score (on a 0-1 scale) of patients with iNPH was significantly lower than that of an age- and gender-matched sample of the general population [0.718 (0.103) vs. 0.870 (0.106); P < 0.001]. The mean 15D score was lower in iNPH patients with moderate or severe depressive symptoms than in patients without depressive symptoms (P = 0.003). According to stepwise multiple linear regression analysis, a higher total iNPHGS score (b = -0.62, P < 0.001) and a higher BDI-21 total score (ß = -0.201, P = 0.025) predicted a lower 15D score; in combination, these explained 51% of the variance in the 15D score (R(2)  = 0.506, P < 0.001). CONCLUSIONS: Idiopathic normal pressure hydrocephalus impairs patients' HRQoL on multiple dimensions, similarly to other chronic diseases. Potentially treatable depressive symptoms contribute greatly to the HRQoL impairment of iNPH patients, but only if they are moderate or severe. The 15D portrayed HRQoL dimensions affected by iNPH in a similar way to broader assessment batteries and thus is a potentially useful tool for treatment evaluation and cost-utility analysis.

Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.

BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-ß levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003). CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-ß in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-ß pathology, both in patients with possible NPH and among the wider population.

CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.

OBJECTIVE: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. METHODS: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aß plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aß42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. RESULTS: The patients with Aß plaques in the cortical biopsy had lower (p = 0.009) CSF Aß42 levels than those with no Aß plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aß42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aß42 and highest tau and p-tau 181 levels in CSF. The Aß42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aß was independently predicted by the APOE ε4 carrier status and age but not by CSF Aß42 or tau levels. CONCLUSIONS: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aß42 and high CSF tau and p-tau levels, respectively.