A case of CLCN2-related leukoencephalopathy with bright tree appearance during aseptic meningitis

Abstract

CLCN2-related leukoencephalopathy (CC2L) is a rare autosomal recessive disorder caused by variants in CLCN2. We report a boy whose brain MRI during an episode of aseptic meningitis at the age of 6 years revealed wide areas of restriction on diffusion-weighted images (DWI) in the cerebral subcortical white matter called bright tree appearance (BTA). In addition to the BTA, high intensity signals were also observed bilaterally in the posterior limbs of the internal capsules, cerebral peduncles, middle cerebellar peduncles, cerebellar white matter, and brain stem (longitudinal pontine bundle) along with low apparent diffusion coefficient values in the same areas. The BTA was transient, seen only during the acute phase of the aseptic meningitis. With the resolution of the infection, his meningitis symptoms completely resolved, but abnormal brain MRI findings remained, other than BTA, which disappeared. At age 13 years, whole exome sequencing revealed a homozygous variant (c.61dupC, p.(Leu21Profs*27)) of CLCN2. He had no intellectual disability or neurological abnormalities. The transient DWI high-intensity signals in the subcortical white matter and the T2 high-intensity signals in the white matter could reflect varying degrees of water imbalance in the extracellular space in myelin sheaths in CC2L.

Introduction

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common pediatric acute encephalopathy in Japan [1]. It is radiologically characterized by delayed reduced diffusion in the subcortical white matter, called bright tree appearance (BTA). BTA mainly appears in the subacute stage of AESD between days 3 and 9. The mechanism assumed to underlie the reduced diffusion in BTA has been reported as the loss of myelinated axons, which enlarges the interstitial space, allowing free movement of protons. The loss of myelinated axons leads to reduced diffusion, resulting in high signal intensity on diffusion-weighted images (DWI) [1]. This MRI finding is a characteristic of AESD, but it is nonspecific.

Chloride channel 2 (ClC-2) encoded by CLCN2 is one of the nine chloride-transporting proteins in the ClC family, members of which are classified as Cl⁻ channels or H⁺/Cl⁻ exchange transporters. Biallelic variants of CLCN2 have been reported in CLCN2-related leukoencephalopathy (CC2L) [2], [3]. We describe a boy with CC2L whose first brain MRI during an episode of aseptic meningitis demonstrated a BTA.