Elsevier

NeuroImage: Clinical

Volume 19, 2018, Pages 848-857
NeuroImage: Clinical

SPG11 mutations cause widespread white matter and basal ganglia abnormalities, but restricted cortical damage

https://doi.org/10.1016/j.nicl.2018.05.031Get rights and content
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Highlights

  • SPG11 leads to widespread White matter (WM) and deep grey matter (GM) damage.

  • Cortical thinning is restricted to motor, limbic and parietal regions.

  • Motor Cortex thinning as well as Spinal Cord and basal ganglia atrophy correlate with motor handicap and disease duration.

  • WM and thalamic damage correlate with cognitive impairment.

  • Progressive damage of GM contrasts with an apparently static WM involvement.

Abstract

SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic Paraplegia. The disease has a wide phenotypic variability indicating many regions of the nervous system besides the corticospinal tract are affected. Despite this, anatomical and phenotypic characterization is restricted. In the present study, we investigate the anatomical abnormalities related to SPG11 mutations and how they relate to clinical and cognitive measures. Moreover, we aim to depict how the disease course influences the regions affected, unraveling different susceptibility of specific neuronal populations. We performed clinical and paraclinical studies encompassing neuropsychological, neuroimaging, and neurophysiological tools in a cohort of twenty-five patients and age matched controls. We assessed cortical thickness (FreeSurfer software), deep grey matter volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI-MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3 T MRI scan. Mean age and disease duration were 29 and 13.2 years respectively. Sixty-four percent of the patients were wheelchair bound while 84% were demented. We were able to unfold a diffuse pattern of white matter integrity loss as well as basal ganglia and spinal cord atrophy. Such findings contrasted with a restricted pattern of cortical thinning (motor, limbic and parietal cortices). Electromyography revealed motor neuronopathy affecting 96% of the probands. Correlations with disease duration pointed towards a progressive degeneration of multiple grey matter structures and spinal cord, but not of the white matter. SPG11-related hereditary spastic paraplegia is characterized by selective neuronal vulnerability, in which a precocious and widespread white matter involvement is later followed by a restricted but clearly progressive grey matter degeneration.

Abbreviations

ACE-R
Addenbrooke's Cognitive Examination Revised
ALS
amyotrophic lateral sclerosis
CA
cord area
CE
cord eccentricity
CMAP
compound muscle action potential
CST
corticospinal tract
DTI
diffusion tensor imaging
FA
fractional anisotropy
GM
grey matter
HSP
hereditary spastic paraplegia
LH
left hemisphere
MD
mean diffusivity
MOCA
Montreal cognitive assessment
NPI
neuropsychiatric inventory
PNP
sensory-motor polyneuropathy
PNS
peripheral nervous system
RH
right hemisphere
ROI
region of interest
SC
spinal cord
SNAP
sensory nerve action potential
SPRS
Spastic Paraplegia Rating Scale
STS
cortex adjacent to the superior temporal sulcus
WM
white matter
WES
whole exome sequencing

Keywords

Complicated hereditary spastic paraplegia
SPG11
Motor neuron disorder
Thinning of the corpus callosum
White matter
Grey matter
Spinal cord

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