Cerebral involvement in axonal CMT neuropathy caused by mitofusion2 mutations

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J Neurol. 2008 Apr 21

Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused

by mitofusin2 mutations.

Brockmann K, Dreha-Kulaczewski S, Dechent P, Bönnemann C, Helms G,

Kyllerman M, Brück W, Frahm J, Huehne K, Gärtner J, Rautenstrauss B.

Dept. of Pediatrics and Pediatric Neurology, Georg August University,

-Koch-Str. 40, 37075, Göttingen, Germany

Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary

axonal Charcot- Marie-Tooth (CMT) neuropathy.

This study aims at further characterization of cerebral white matter

alterations observed in patients with MFN2 mutations. Molecular

genetic, magnetic resonance imaging (MRI), magnetic resonance

spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations

were performed in four unrelated patients aged 7 to 38 years with

early onset axonal CMT neuropathy.

Three distinct and so far undescribed MFN2 mutations were detected.

Two patients had secondary macrocephaly and mild diffuse

predominantly periventricular white matter alterations on MRI. In

addition, one boy had symmetrical T2-hyperintensities in both

thalami.

Two patients had optic atrophy, one of them with normal MRI. In three

patients proton MRS revealed elevated concentrations of total N-

acetyl compounds (neuronal marker), total creatine (found in all

cells) and myo-inositol (astrocytic marker) in cerebral white and

gray matter though with regional variation. These alterations were

most pronounced in the two patients with abnormal MRI. DTI of these

patients revealed mild reductions of fractional anisotropy and mild

increase of mean diffusivity in white matter.

The present findings indicate an enhanced cellular density in

cerebral white matter of MFN2 neuropathy which is primarily due to a

reactive gliosis without axonal damage and possibly accompanied by

mild demyelination.