Clinical and Pathological Features of an Autosomal Dominant, Adult-Onset Leukodystrophy Simulating Chronic Progressive Multiple Sclerosis

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

“…Tremor, previously reported in LMNB1 ‐related ADLD,2, 7 was present in less than half of the patients and caused major complaint in 1 patient. We found no signs of polyneuropathy, confirming earlier reports 2, 3, 4, 5, 24. A new observation in this follow‐up study is that sensory impairment started in the distal part of the legs and ascended over time to the thoracic level, consistent with myelopathy, and development of flaccid paralysis of the lower limbs.…”

“…This follow‐up study gives a strong indication that spinal cord involvement is clinically significant in this type of leukodystrophy and may also, at least partly, explain the autonomic dysfunction. Previous histopathological studies have verified involvement of the spinal cord in a patient already at 3 years after onset of symptoms5 and more‐severe changes in a patient with longer disease duration 24. In our study, clinical assessment, radiological findings, and neurophysiological examinations indicate myelopathy.…”

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

“…These vacuoles became confluent and created a "cracked" appearance. 7 It is possible that the slighter histopathologic changes in the spinal cord of our patient represent an earlier stage of the disease. The patient examined by Schwankhaus et al 7 had a disease duration of Ͼ10 years and had been admitted to a care facility, whereas the patient examined in our study had experienced symptoms for only 3 years and was still completely independent.…”

“…Histopathologic examination of the spinal cord has been reported in 1 patient. 7 In this case, there were vacuolar changes and loss of myelin in the white matter, whereas gross visual inspection had shown changes in the anterior, lateral, and dorsal columns. In another patient, no macroscopic changes were found in the spinal cord at postmortem examination.…”

“…3,7,14 We postulate that the white matter in the spinal cord is affected in adult-onset ADLD with autonomic symptoms and, further, that spinal cord white matter is affected even before the onset of clinical symptoms. A pattern of early involvement of the corticospinal tract appeared in the brain, but in the spinal cord, the entire white matter was affected in all patients.…”