Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: a TMS study.

Dipartimento di Nerurologia, Oftalmologia, Otorinolaringoiatria e Psichiatria, Università di Palermo, Italy.
Journal of the Neurological Sciences (Impact Factor: 2.24). 09/2005; 235(1-2):19-22. DOI: 10.1016/j.jns.2005.03.050
Source: PubMed

ABSTRACT The aim of the study was to explore excitability of a motor and a non-motor (visual) area in patients affected by Friedreich ataxia and to correlate neurophysiological data with clinical parameters. Seven patients (3M/4F) and ten healthy controls (5M/5F) participated in the study. The hot-spot for activation of right abductor pollicis brevis was checked by means of a figure-of-eight coil and the motor threshold (MT) on this point was recorded. The phosphene threshold (PT) was measured by means of a focal coil over the occipital cortex as the lower intensity of magnetic stimulation able to induce the perception of phosphenes. The patients showed a significantly higher mean PT (p<.03) and MT values (p<.001) than controls. In all but one patient unable to perceive phosphenes (42% vs. 50% of controls), TMS at 100% intensity did not elicit motor response at rest. The difference in percentage of patients (57.1%) and controls (100%) with motor responses was nearly significant. The size of GAA1 expansion showed significant correlations with PT and MT values. The results of our study showed that FA patients had reduced cortical activation, involving both the motor and the visual cortex. The cortical involvement in these patients seems to be mainly genetically determined. The study provides the first evidence of cortical dysfunction in patients with genetically defined Friedreich ataxia.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We recently demonstrated that people with FRDA have impairment in motor planning - most likely because of pathology affecting the cerebral cortex and/or cerebello-cortical projections. We used the Simon interference task to examine how effective 13 individuals with FRDA were at inhibiting inappropriate automatic responses associated with stimulus-response incompatibility in comparison with control participants. Participants had to respond to arrow targets according to two features which were either congruent or incongruent. We found that individuals with FRDA were differentially affected in reaction time to incongruent, compared with congruent stimuli, when compared with control participants. There was a significant negative correlation between age of onset and the incongruency effect, suggesting an impact of FRDA on the developmental unfolding of motor cognition, independent of the effect of disease duration. Future neuroimaging studies will be required to establish whether this dysfunction is due to cerebellar impairment disrupting cerebro-ponto-cerebello-thalamo-cerebral loops (and thus cortical function), direct primary cortical pathology, or a possible combination of the two.
    Brain and Cognition 02/2011; 76(1):140-5. · 2.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Friedreich ataxia (FRDA), the most common of the hereditary ataxias, is an autosomal recessive, multisystem disorder characterised by progressive ataxia, sensory symptoms, weakness, scoliosis and cardiomyopathy. FRDA is caused by a GAA expansion in intron one of the FXN gene, leading to reduced levels of the encoded protein frataxin, which is thought to regulate cellular iron homeostasis. The cerebellar and spinocerebellar dysfunction seen in FRDA has known effects on motor function; however until recently slowed information processing has been the main feature consistently reported by the limited studies addressing cognitive function in FRDA. This chapter will systematically review the current literature regarding the neuropathological and neurobehavioural phenotype associated with FRDA. It will evaluate more recent evidence adopting systematic experimental methodologies that postulate that the neurobehavioural phenotype associated with FRDA is likely to involve impairment in cerebello-cortico connectivity.
    Advances in experimental medicine and biology 01/2012; 769:169-84. · 1.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study sought to characterise force variability and motor overflow in 12 individuals with Friedreich ataxia (FRDA) and 12 age- and gender-matched controls. Participants performed a finger-pressing task by exerting 30 and 70 % of their maximum finger force using the index finger of the right and left hand. Control of force production was measured as force variability, while any involuntary movements occurring on the finger of the other, passive hand, was measured as motor overflow. Significantly greater force variability in individuals with FRDA compared with controls is indicative of cortico-cerebellar disruption affecting motor control. Meanwhile, significantly greater motor overflow in this group provides the first evidence of possible abnormal inter-hemispheric activity that may be attributable to asymmetrical neuronal loss in the dentate nucleus. Overall, this study demonstrated a differential engagement in the underlying default processes of the motor system in FRDA.
    Journal of Neurology 03/2013; · 3.58 Impact Factor