Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings

Abstract

Objective: Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD.

Methods: We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients.

Results: The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation.

Interpretation: APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy.

Figure 1

Kaplan–Meier analyses indicate the natural history of 50 adult polyglucosan body disease patients for time to bladder dysfunction, difficulty walking, use of a wheelchair, and death.

Figure 2

Typical cerebral and spinal pattern is shown in adult polyglucosan body disease patients. (A) T1 sagittal scans show important medullary and spinal atrophy and mild vermian atrophy. (B) Fluid attenuated inversion recovery axial scans show hyperintense white matter abnormalities in the periventricular regions, with occipital predominance, the external capsule and the posterior limb of the internal capsule (dashed circles), the medial edges of the inferior and middle cerebellar peduncles (arrows), and the pyramidal tracts and medial lemniscus of the medulla and pons (plain circles).

Figure 3

An adult polyglucosan body disease patient with medullary atrophy but normal white matter is shown in the early stages of her disease.