The Cerebellum Looks Normal in Friedreich Ataxia

Letters to the Editor Letters to the Editor

Published online before print January 17, 2013, doi: 10.3174/ajnr.A3480
AJNR 2013 34: E22

M. Mascalchia
aRadiodiagnostic Section
Department of Clinical Physiopathology
University of Florence
Florence, Italy

I read with great interest the review by Vedolin et al1 and much appreciated their effort to provide neuroradiologists with some help in the diagnosis of the child presenting with ataxia. However, taking into account the practical approach the authors pursued, I would like to draw attention to the information they provided about the most common cause of inherited ataxia, namely Friedreich ataxia (FRDA).

They mentioned FRDA in the group of the most common causes of cerebellar ataxia in childhood showing a degenerative pattern on MR imaging that comprises cerebellar atrophy and signal changes in the cerebellum, brain stem, or both on T1- and T2-weighted images.1 However, the few reports mentioning cerebellar atrophy in FRDA were invariably based on subjective visual assessment of the cerebellar size or were focused on patients with late-onset FRDA, while morphometric assessment failed to show decreased cerebellar volume in patients with FRDA with typical disease onset before 25 years of age compared with age-matched controls.2 Lack of cortical cerebellar atrophy in FRDA was confirmed in a voxel-based morphometry study that, however, demonstrated volume loss of the deep peridentate WM.3 Preservation of the cortex is in line with the pathologic descriptions of FRDA emphasizing that cerebellar damage involves the dentate nuclei and deep cerebellar WM.4 A nonspecific finding emerging in FRDA is atrophy and microstrutural damage of the superior cerebellar peduncles that are correlated with disease duration and severity of the neurologic deficit.2,3 Because the superior cerebellar peduncle contains most of the efferent fibers of the dentate nucleus, which is a site of primary neurodegeneration in FRDA,4the superior cerebellar peduncle alteration appears a promising biomarker for this disease but is not visually apparent and requires morphometry or computation of DTI measurements to be detected. Also, the increased magnetic susceptibility effects due to iron deposition observed in the cerebellar dentate nuclei of patients with FRDA require specific T2*acquisitions and postprocessing.5 In conclusion, visual assessment of routine MR imaging in FRDA reveals a normal cerebellum for its size and signal.6

It is anticipated that integration of the above information might enhance the practical value of the review. In fact, evidence of a visually normal cerebellum in a patient presenting with ataxia in childhood or adolescence helps support the diagnosis of FRDA and substantially decreases the possibility of other less common recessively inherited ataxias7 and infantile-onset spinocerebellar ataxias, in which diffuse cerebellar atrophy can be present.

References

  1. Vedolin L, Gonzalez G, Souza CF, et al. Inherited cerebellar ataxia in childhood: a pattern-recognition approach using brain MRI. AJNR Am J Neuroradiol May 17 2012 [Epub ahead of print] » Search Google Scholar
  2. Akhlaghi H, Corben L, Georgiou-Karistianis N, et al. Superior cerebellar peduncle atrophy in Friedreich’s ataxia correlates with disease symptoms.Cerebellum 2011;10:81–87 » CrossRef » Medline
  3. Della Nave R, Ginestroni A, Tessa C, et al. Brain white matter tracts degeneration in Friedreich ataxia: an in vivo MRI study using tract-based spatial statistics and voxel based morphometry. NeuroImage 2008;40:19–25 » CrossRef » Medline
  4. Koeppen AH. Friedreich’s ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci 2011;303:1–12 » CrossRef » Medline
  5. Waldvogel D, van Gelderen P, Hallet M. Increased iron in the dentate nucleus of patients with Friedreich’s ataxia. Ann Neurol 1999;46:123–25 » CrossRef » Medline
  6. Schols L, Amoiridis G, Przuntek H, et al. Friedreich’s ataxia: revision of the phenotype according to molecular genetics. Brain 1997;120(pt 12):2131–40 » Abstract/FREE Full Text
  7. Anheim M, Tranchant C, Koenig M. The autosomal recessive cerebellar ataxias. N Engl J Med 2012;366:636–46 » CrossRef » Medline

Reply

Published online before print January 17, 2013, doi: 10.3174/ajnr.A3481
AJNR 2013 34: E23

L. Vedolina
aNeuroradiology Section
Hospital Moinhos de Vento
Porto Alegre, Brazil

We greatly appreciate Dr Mascalchi’s interest in our article “Inherited Cerebellar Ataxia in Childhood: A Pattern-Recognition Approach Using Brain MRI.”1 We agree that many cases of Friedreich ataxia (FRDA) have normal MR imaging findings at the time of diagnosis and that a visually normal cerebellum in a child with ataxia usually suggests FRDA. We also concur that volume loss and decreased fractional anisotropy by diffusion tensor imaging of the superior cerebellar peduncles and iron deposition on T2* are potential biomarkers for this disease.2,3

References

  1. Vedolin L, Gonzalez G, Souza CF, et al. Inherited cerebellar ataxia in childhood: a pattern-recognition approach using brain MRI. AJNR Am J Neuroradiol May 17 2012 [Epub ahead of print] » Search Google Scholar
  2. Della Nave R, Ginestroni A, Diciotti S, et al. Axial diffusivity is increased in the degenerating superior cerebellar peduncles of Friedreich’s ataxia. Neuroradiology 2011;53:367–72 » CrossRef » Medline
  3. Koeppen AH, Michael SC, Knutson MD, et al. The dentate nucleus in Friedreich’s ataxia: the role of iron-responsive proteins. Acta Neuropathol 2007;114:163–73 » CrossRef » Medline
The Cerebellum Looks Normal in Friedreich Ataxia