Steffi Dreha-Kulaczewski

Publications (4)19.72 Total impact

• Article: Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism.

  Robert Steinfeld, Marcel Grapp, Ralph Kraetzner, Steffi Dreha-Kulaczewski, Gunther Helms, Peter Dechent, Ron Wevers, Salvatore Grosso, Jutta Gärtner
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  ABSTRACT: Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency. We identified an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 (FOLR1) gene coding for folate receptor alpha (FRalpha). Three patients carrying FOLR1 mutations developed progressive movement disturbance, psychomotor decline, and epilepsy and showed severely reduced folate concentrations in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) demonstrated profound hypomyelination, and MR-based in vivo metabolite analysis indicated a combined depletion of white-matter choline and inositol. Retroviral transfection of patient cells with either FRalpha or FRbeta could rescue folate binding. Furthermore, CSF folate concentrations, as well as glial choline and inositol depletion, were restored by folinic acid therapy and preceded clinical improvements. Our studies not only characterize a previously unknown and treatable disorder of early childhood, but also provide new insights into the folate metabolic pathways involved in postnatal myelination and brain development.
  The American Journal of Human Genetics 10/2009; 85(3):354-63. · 10.60 Impact Factor
• Source

  Available from: Gunther Helms

  Article: Serial proton MR spectroscopy and diffusion tensor imaging in infantile Balo's concentric sclerosis.

  Steffi F Dreha-Kulaczewski, Gunther Helms, Peter Dechent, Sabine Hofer, Jutta Gärtner, Jens Frahm
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  ABSTRACT: Proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) yield different parameters for characterizing the evolution of a demyelinating white matter disease. The purpose was to elucidate biochemical and microstructural changes in Balo's concentric sclerosis lesions and to correlate the findings with the clinical course. Localized short-echo time MRS and DTI were performed over 6 years in a left occipital lesion of a female patient (age at onset 13.8 years) with Balo's concentric sclerosis. A right homonym hemianopsia persisted. Metabolite patterns were in line with initial active demyelination followed by gliosis and partial recovery of neuroaxonal metabolites. Fractional anisotropy and mean diffusivity of tissue water remained severely altered. Fiber tracking confirmed a disruption in the geniculo-calcarine tract as well as involvement of the corpus callosum. MRS and DTI depict complementary parameters, but DTI seems to correlate better with clinical symptoms.
  Neuroradiology 11/2008; 51(2):113-21. · 2.82 Impact Factor
• Article: Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

  Knut Brockmann, Steffi Dreha-Kulaczewski, Peter Dechent, Carsten Bönnemann, Gunther Helms, Marten Kyllerman, Wolfgang Brück, Jens Frahm, Kathrin Huehne, Jutta Gärtner, Bernd Rautenstrauss
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  ABSTRACT: 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.
  Journal of Neurology 05/2008; 255(7):1049-58. · 3.47 Impact Factor
• Article: Cerebral metabolic and structural alterations in hereditary spastic paraplegia with thin corpus callosum assessed by MRS and DTI.

  Steffi Dreha-Kulaczewski, Peter Dechent, Gunther Helms, Jens Frahm, Jutta Gärtner, Knut Brockmann
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  ABSTRACT: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a complicated form of autosomal-recessive hereditary spastic paraplegia. Characteristic clinical features comprise progressive spastic gait, cognitive impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus callosum and non-progressive white matter (WM) alterations. To study the extent of axonal involvement, we performed localized proton magnetic resonance spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient with HSP-TCC at 20 and 25 years of age. The second investigation included diffusion tensor imaging (DTI). While MRS of the GM was normal, affected WM was characterized by major metabolic alterations such as reduced concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and phosphocreatine, and choline-containing compounds as well as elevated levels of myo-inositol. These abnormalities showed progression over a period of 5 years. DTI revealed increased mean diffusivity as well as reduced fractional anisotropy in periventricular WM. The metabolic and structural findings are consistent with progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation-histopathological changes known to occur in HSP-TCC. Our results are in agreement with the hypothesis that the primary pathological process in HSP-TCC affects the axon, possibly due to impaired axonal trafficking.
  Neuroradiology 01/2007; 48(12):893-8. · 2.82 Impact Factor