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Incidence, diagnostic criteria and outcome following ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus in a memory clinic population: a prospective observational cross-sectional and cohort study.

ABSTRACT: OBJECTIVE:To evaluate diagnostic criteria for idiopathic normal pressure hydrocephalus (INPH) among patients with memory impairment, and to estimate the incidence of INPH. DESIGN:Prospective observational cross-section and cohort study of diagnostic accuracy. SETTING:Memory Disorders Clinic following referral by the medical practitioners. PARTICIPANTS:408 consecutive patients enrolled 2010-2014. OUTCOME MEASURES:Reference diagnostic test was the clinical judgement of an experienced specialist based on the presence of cognitive impairment and/or balance and gait disorders in the presence of dilated ventricles. Mini-Mental State Examination (MMSE), Tinetti balance and gait tests were performed before and 12 months after ventriculoperitoneal shunt surgery. The association between reference diagnosis, clinical and brain CT scan measurements was estimated by multivariate Poisson regression. Triage index diagnostic test scores were calculated from the regression coefficients, with diagnostic thresholds selected using receiver operating characteristic analysis. RESULTS:The presence of balance and/or gait disorders, especially fear of falling, difficulty standing on toes/heals, urinary disturbances, ventriculomegaly with Evans ratio greater than Combined Diagnostic Threshold (0.377-{Maximum width of posterior horns*0.0054}), strongly predict the diagnosis of INPH; while hallucinations and/or delusions and forgetfulness reduce the likelihood of the diagnosis. This triage index test had high sensitivity (95.2%) and specificity (91.7%). 62 of 408 (15%) participants with cognitive impairment had INPH, an incidence of 11.9/100 000/year and 120/100 000/year over 75 years. 96% of participants following shunting, compared with 45% of the non-shunted, improved by over 25% of available measurable improvement in either MMSE or balance/gait scores (51% difference; 95%?CI 28% to 74%; p<0.001), and 56% vs 5% improved by over 50% of maximum in both (51% difference; 95%?CI 30% to 73%; p<0.001). CONCLUSION:The triage index test score is a simple tool that may be useful for physicians to identify INPH diagnoses and need for referral for shunt surgery, which may improve cognitive, balance and gait functioning.

SUBMITTER: Razay G

PROVIDER: S-EPMC6924805 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Incidence, diagnostic criteria and outcome following ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus in a memory clinic population: a prospective observational cross-sectional and cohort study.

Razay George G Wimmer Melissa M Robertson Iain I

BMJ open 20191203 12

<h4>Objective</h4>To evaluate diagnostic criteria for idiopathic normal pressure hydrocephalus (INPH) among patients with memory impairment, and to estimate the incidence of INPH.<h4>Design</h4>Prospective observational cross-section and cohort study of diagnostic accuracy.<h4>Setting</h4>Memory Disorders Clinic following referral by the medical practitioners.<h4>Participants</h4>408 consecutive patients enrolled 2010-2014.<h4>Outcome measures</h4>Reference diagnostic test was the clinical judge ...[more]

PMID: 31796471

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Project description:The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging.

Dataset Information

Incidence, diagnostic criteria and outcome following ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus in a memory clinic population: a prospective observational cross-sectional and cohort study.

Publications

Incidence, diagnostic criteria and outcome following ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus in a memory clinic population: a prospective observational cross-sectional and cohort study.

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