Arterial Spin Labeled Cerebral Blood Flow to Diagnose Normal-Pressure Hydrocephalus: A Pilot Study

The diagnosis of normal-pressure hydrocephalus (NPH) is often complicated due to deficiencies of the objective measures currently used after test drainage of CSF. We used Arterial Spin Labeled Magnetic Resonance Imaging (ASL-MRI)-a novel, simplified, completely non-invasive, radiation-free method-to measure global cerebral blood flow (CBF) before and after performing a large-volume lumbar puncture (LVLP) in patients suspected of NPH.

We compared baseline ASL-CBF in 20 patients (65-91 years old, mean: 75 years; 11 men) with history of recurrent falls from unsteady gait, urinary incontinence, cognitive decline, and ventriculomegaly (Evans index > 0.30). After LVLP under fluoroscopy draining 20-53 mL of CSF we measured ASL-CBF and compared the cerebral perfusion with baseline values for whole brain, predefined cortical regions, deep grey nuclei, and periventricular white matter. Correlation was assessed with changes in gait speed and balance, neuropsychology testing and urinary incontinence.

Post-LVLP all patients had significant increase in global ASL-CBF with mean values rising from 39 to 45 mL/100 g/min (P < 0.01). CBF enhancement was notable in gray matter regions, thalamus and periventricular frontal white matter. Draining ≤40 mL of CSF resulted on average CBF increase of 0.9 mL/100 g/min compared with 5.2 mL/100 g/min after draining 50 mL of CSF (P < 0.01) indicating a dose-response relationship whereby draining <40 mL of CSF may not be adequate to diagnose NPH.

We confirmed the occurrence of CBF hypoperfusion in NPH. Linear mixed-effects model for regional blood flow analysis confirmed consistent enhancement of cerebral perfusion in all evaluated regions post-lumbar puncture. Exploratory analysis to correlate baseline CBF with the magnitude of change post-lumbar puncture revealed a negative correlation (Pearson r = -0.819 P = 0.000) indicating that patients with lower baseline CBF exhibited larger increases in perfusion after CSF drainage. There was a positive correlation between enhancement of CBF and improvement of gait speed and balance. Using ASL-MRI, we have demonstrated that global cerebral hypoperfusion is a constant feature of NPH that improves with CSF drainage. As a result, the clinical diagnosis of NPH can be greatly simplified using ASL-MRI.