Pathologically Verified Corticobasal Degeneration Mimicking Richardson's Syndrome Coexisting with Clinically and Radiologically Shunt-Responsive Normal Pressure Hydrocephalus

Abstract

Background: Normal pressure hydrocephalus (NPH) manifests as gait instability, cognitive impairment, and urinary incontinence. This clinical triad of NPH sometimes occurs with ventriculomegaly in patients with neurodegenerative disease. Patients with pathologically verified neurodegenerative diseases, such as progressive supranuclear palsy (PSP), have received antemortem diagnoses of NPH.

Objectives: This study presents clinical and pathological features of a patient with pathologically verified corticobasal degeneration (CBD) coexisting with clinically shunt-responsive NPH.

Methods: We performed clinical, radiological, and pathological evaluations in a patient with CBD whose antemortem diagnosis was PSP Richardson's syndrome (PSP-RS) coexisting with shunt-responsive NPH.

Results: A 59-year-old woman developed bradykinesia and gait instability and then frequent falls, urinary incontinence, and supranuclear vertical gaze palsy followed. At 63 years of age, her gait disturbance and urinary incontinence had deteriorated rapidly, and cognitive impairment was disclosed. There were typical findings of NPH with ventriculomegaly and disproportionately enlarged subarachnoid space hydrocephalus as well as a 2-layer appearance with decreased and increased cerebral blood perfusion. Shunt placement ameliorated gait instability for more than 1 year and improved radiological indicators of NPH. However, atrophy of the midbrain progressed with time after transient increases in size. Although the antemortem diagnosis was probable PSP-RS, pathological evaluation verified CBD. There were severe discontinuities of the ependymal lining of the lateral ventricles and subependymal rarefaction and gliosis with tau-positive deposition.

Conclusions: Shunt surgery could ameliorate NPH symptoms in patients with 4-repeat tauopathies. Careful assessments of clinical findings are necessary to predict the benefits of shunts as a therapeutic option for patients with neurodegenerative diseases coexisting with NPH.

Keywords: corticobasal degeneration; neurodegenerative NPH; normal pressure hydrocephalus; progressive supranuclear palsy; shunt surgery.

FIG. 1

Neuroradiological assessments at different time points. (A) The anteroposterior midbrain diameter, callosal angle, and Evans index on magnetic resonance imaging gradually decrease over time. (B) The 2‐layer appearance consisting of decreased blood flow around the corpus callosum (blue arrows) and enhanced perfusion in areas surrounding the cingulate gyrus (red arrows) on brain perfusion single‐photon emission computed tomography images using the easy Z‐score imaging system program.

FIG. 2

Series of brain computed tomography images before and after shunt surgery. Ventriculomegaly is improved until the late stage of the disease (upper row). The anteroposterior midbrain diameter shows a transient improvement after shunt surgery; however, this deteriorates again at 22 months after surgery (lower row).

FIG. 3

Neuropathological findings. (A,B) Mild cerebral atrophy of the frontal operculum and dilated lateral ventricles with thinning of the corpus callosum. (C) Tau‐positive astrocytic plaque and (D) coiled bodies and threads in the precentral gyrus (immunohistochemistry using an AT8 antibody). (E,F) Discontinuities of the ependymal lining, subependymal rarefaction, and gliosis (E, hematoxylin and eosin staining; F, Gallyas‐Braak staining). (G) Tau‐positive deposition in the subependymal region (immunohistochemistry using an AT8 antibody). Asterisks represent the lateral ventricle. (H) Western blot analysis of sarkosyl‐insoluble tau from the brain probed using a T46 antibody. CBD, corticobasal degeneration; PSP, progressive supranuclear palsy.