Brain shrinkage found in SPG 2 HSP

Changes also in the myelin sheath around axons


SPG 2 HSP is associated with Pelizaeus-Merzbacher disease, as both conditions are related to mutations of the PLP gene. SPG 2 HSP is passed on by X-linked inheritance where females are generally the carrier and males are affected. SPG 2 HSP can be pure or complicated.


The study found that most patients experienced brain shrinkage over time and changes in the myelin sheath around axons of neurons were also discovered, suggesting that both neurons and oligodendrocytes (cells responsible for myelination) are affected in this form of HSP.




Brain magnetic resonance imaging (MRI) motor development score (MDS) correlations were used to analyze the natural time-course of hypomyelinating PLP1-related disorders (Pelizaeus-Merzbacher disease [PMD] and spastic paraplegia type 2).



Thirty-five male patients (ranging from 0.7-43.5y at the first MRI) with PLP1-related disorder were prospectively followed over 7 years. Patients were classified according to best motor function acquired before 5 years (MDS) into five categories (from PMD0 without motor acquisition to PMD4 with autonomous walking). We determined myelination and atrophy scores and measured corpus callosum area, volume of cerebellum, white matter and grey matter on 63 MRI.



Age-adjusted multivariate analysis revealed that patients with PMD0-1 had higher-severity atrophy scores and smaller corpus callosum area than did patients with PMD2 and PMD3-4. Myelination score increased until 12 years. There was evidence that the mean myelination differed in frontal white matter, arcuate fibres, and internal capsules among the groups. Most patients showed worsening atrophy (brain, cerebellum, corpus callosum), whereas grey matter and white matter proportions did not change.



Brain atrophy and myelination of anterior cerebral regions appear to be pertinent biomarkers of motor development. The time-course of inter- and intra-individual cerebral white matter and grey matter atrophy suggests that both oligodendrocytes and neurons are involved in the physiopathology of PLP1-related disorders.


SOURCE: Dev Med Child Neurol. 2016 Jan 19. doi: 10.1111/dmcn.13025. [Epub ahead of print] © 2016 Mac Keith Press. PMID: 26786043 [PubMed – as supplied by publisher]


Time-course of myelination and atrophy on cerebral imaging in 35 patients with PLP1-related disorders.


Sarret C1,2, Lemaire JJ1,3, Tonduti D4,5, Sontheimer A1, Coste J1, Pereira B1,6, Feschet F1, Roche B1, Boespflug-Tanguy O4,7.


1Image-Guided Clinical Neuroscience and Connectomics (IGCNC), Clermont University, University of Auvergne, Clermont-Ferrand, France.

2Department of Paediatrics, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

3Department of Neurosurgery, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

4Inserm U1141 Paris Diderot Sorbonne University-Paris Cité, DHU PROTECT, Robert Debré Hospital, Paris, France.

5Department of Child Neurology, Neurological Institute C. Besta Foundation IRCCS, Milan, Italy.

6Biostatistics Unit (DRCI), Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

7Department of Child Neurology and Metabolic Diseases, Leukodystrophies Reference Centre, Robert Debré Hospital, Paris, France.



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