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Characterizing POLG Ataxia: Clinics, Electrophysiology and Imaging

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Abstract

Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Thirteen patients with POLG-A were assessed by standardized clinical investigation, nerve conduction studies, motor-evoked potentials, magnetic resonance imaging (MRI) and transcranial sonography (TCS). The findings were compared with 13 matched patients with Friedreich’s ataxia (FA). In addition to the well-known POLG-associated features of chronic external ophthalmoplegia (100 %), areflexia to the lower extremity (100 %), impaired vibration sense (100 %), bilateral ptosis (69 %) and epilepsy (38 %), also hyperkinetic movement disorders were frequent in POLG-A patients, including chorea (31 %), dystonia (31 %) and myoclonus (23 %). Similar to FA, polyneuropathy was of sensory axonal type (100 %). In contrast to FA, none of the POLG-A patients showed impaired central motor conduction. TCS demonstrated less enlargement of the fourth ventricle and more diffuse cerebellar hyperechogenicity in POLG-A. Corresponding to TCS, MRI revealed no or only mild cerebellar atrophy in most POLG-A patients (85 %). POLG ataxia presents with the clinical characteristics of both afferent and cerebellar ataxia. Cerebellar alterations diffusely involve various parts of the cerebellum, yet cerebellar atrophy is generally mild. POLG-A presents with a high load of distinct non-ataxia features, namely, sensory neuropathy, external ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic movement disorders. Involvement of the corticospinal tract, however, is rare.

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Abbreviations

DN:

Dentate nucleus

FA:

Friedreich’s ataxia

LN:

Lentiform nucleus

MRI:

Magnetic resonance imaging

PEO:

Chronic progressive external ophthalmoplegia

POLG:

Polymerase gamma

POLG-A:

POLG-associated ataxia

SN:

Substantia nigra

TCS:

Transcranial sonography

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Potential Conflicts of Interest

The authors do not have any conflicts of interest related to this work.

Research Support Related to this Work

LS was supported by a grant from the German Ministry for Education and Research (BMBF) to mitoNET (01GM0864). MS received a grant from the Volkswagen Stiftung (Az. II/85158).

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Correspondence to Ludger Schöls.

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Synofzik, M., Srulijes, K., Godau, J. et al. Characterizing POLG Ataxia: Clinics, Electrophysiology and Imaging. Cerebellum 11, 1002–1011 (2012). https://doi.org/10.1007/s12311-012-0378-2

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  • DOI: https://doi.org/10.1007/s12311-012-0378-2

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