Neurocognitive deficits and diffusion MR imaging abnormalities in a case of adult-onset autosomal dominant leukodystrophy

Abstract

Autosomal dominant adult-onset leukodystrophy (ADLD) is a progressive hereditary disease caused by duplication of Lamin B1 on chromosome 5q23.2. It is characterized by autonomic dysregulation, pyramidal signs, and cerebellar dysfunction. Since the first description in 1984, no authors have reported on its neurocognitive sequelae or attempted to quantify the severity of white matter changes. Herein we report a case of ADLD presenting with progressive cognitive changes leading to dementia and its associated white matter damage using diffusion MR imaging. Case reportA 55-year-old man was evaluated for a 10-year history of weakness of the legs (left > right) and gait disturbances. In the last three years, he also complained of significant changes in his cognition. A detailed history revealed changes in attention, memory and organizational skills. showed that compared to our control paired for age and education, FA was 12.5% lower in the patient, while ADC diffusivities (radial and axial) were 5% higher. Preliminary results from HARDI tractography robust to fiber crossing [2] showed chaotic and incoherently organized tracts (e.g., corticospinal tract; see Figure 2G-H). DiscussionTo this date, ADLD had only been known for its progressive onset of autonomic, pyramidal and cerebellar symptoms [3,4]. We report of a 55 year-old ADLD patient with significant deficits in attention, memory, visuoconstruction and executive skills. Deficits particularly affect frontal-subcortical pathways and give rise to

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

“…Detailed neuropsychological testing has not been performed in a larger series of patients with LMNB1 ‐related ADLD. Below‐average test results or cognitive deficits have been described in a 47‐year‐old German patient and a 55‐year‐old Canadian patient, respectively. In an Italian family, mild cognitive impairment and dementia were reported .…”

LMNB1‐duplication mediated nuclear architecture alteration and demyelination of cerebral white matter in a patient with ADLD

“…Brain imaging corroborated these findings with confluent and diffuse hyperintensities in the hemispheric white matter as well as the involvement of the superior, middle and inferior cerebellar peduncles, mild cerebellar atrophy and bilateral parietal atrophy. These brain regions are known to participate in complex attention, visuospatial and executive skills, which were all affected in the reported patient and other members of her family [11].…”

LMNB1-Related Adult-Onset Autosomal Dominant Leukodystrophy Presenting as Movement Disorder: A Case Report and Review of the Literature

“…In several atypical patients, however, autonomic dysfunction could occur after somatic motor dysfunction, or fail to be detected (Brussino et al, 2010; Giorgio et al, 2013; Potic et al, 2013). Some updated reports pointed out that cognitive impairment, auditory or visual abnormalities, cardiovascular and skin noradrenergic failure, and REM sleep behavior disorder (RBD) may be clinical features of ADLD (Guaraldi et al, 2011; Flanagan et al, 2013; Laforce et al, 2013; Sandoval-Rodriguez et al, 2017; Table 1). Compared with the onset of clinical symptoms, MRI findings have been observed about a decade earlier (Finnsson et al, 2015).…”