Hereditary Adult-Onset Leukodystrophy Simulating Chronic Progressive Multiple Sclerosis

Abstract

We studied a large kindred with a chronic progressive neurologic disorder affecting at least 10 men and 11 women in four generations in a pattern compatible with autosomal dominant inheritance. In 20 of the affected subjects, evaluated before the availability of computerized tomography and without regard to family history, the diagnosis was multiple sclerosis. Symptoms of the neurologic disorder begin in the fourth and fifth decades and include cerebellar, pyramidal, and autonomic abnormalities. The autonomic symptoms, which involve bowel and bladder regulation and orthostatic hypotension, may be the earliest changes but are frequently disregarded. Survival for 20 years after onset is common. The CT scan is striking and shows a symmetrical decrease in white-matter density, beginning in the frontal lobes but extending to all of the centrum ovale and the cerebellar white matter. Limited pathological observation reveals gross white-matter degeneration with microscopic vacuolation, preservation of U fibers and cortical structures, and no inflammatory changes or reactive gliosis. Because of its hereditary basis, the disorder should be susceptible to genetic definition and ultimately to treatment or prevention.

LMNB1‐related autosomal‐dominant leukodystrophy: Clinical and radiological course

“…In an Italian family, mild cognitive impairment and dementia were reported 10. Eldridge's original report concluded that intellectual acuity is often well maintained 2. In our study, patients did not complain of cognitive impairment or they only showed mild cognitive deficit early in the disease course.…”

“…On follow‐up examinations, only 3 subjects exhibited a decrease in cross‐sectional area or diameter, defined as >8mm2 or >1.5mm difference between two measurements. These cut‐off points were estimated based on Bland‐Altman plots of the variability between two readings.…”

“…In the original family reported by Eldridge et al,2 onset was reported from the fourth to fifth decade. Two of our patients reported gait difficulties preceding bladder control problems.…”

MR Imaging Characteristics and Neuropathology of the Spinal Cord in Adult-Onset Autosomal Dominant Leukodystrophy with Autonomic Symptoms

“…1 Adult-onset autosomal dominant leukodystrophy (ADLD; Online Mendelian Inheritance in Man accession number 169500) is thus a rarity and was initially reported in 1984 in an Irish-American kindred. 2 The same disease was also described in 2 Swedish families and named adult-onset ADLD with autonomic symptoms. 3 Similar disorders have been described in Japan and Italy, though these may be separate clinical entities.…”

“…In another patient, no macroscopic changes were found in the spinal cord at postmortem examination. 2 In this study, we describe MR imaging findings of the spinal cord of 12 members of 2 families with adult-onset ADLD with autonomic symptoms. We also describe spinal cord neuropathology in 1 patient.…”