Browsing by Author "Pandolfo, Massimo"

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    Electrophysiological evidence for limited progression of the proprioceptive impairment in Friedreich ataxia
    (ELSEVIER IRELAND LTD, 2020-02-01) Naeije, G.; Bourguignon, Mathieu; Wens, V.; Marty, B.; Goldman, S.; Hari, Riitta; Jousmäki, Veikko; Pandolfo, Massimo; De Tiège, Xavier; Department of Art; Department of Neuroscience and Biomedical Engineering; Université libre de Bruxelles
    Friedreich ataxia (FRDA) is the most common recessive ataxia in Caucasians. Over 95% of patients are homozygous for the hyperexpansion of a GAA triplet repeat in the first intron of the frataxin (FXN) gene, which represses FXN expression via an epigenetic mechanism. Most residual FXN expression comes from the chromosome with the shortest repeat (GAA1), whose length has been shown to correlate with age at symptom onset and with disease severity. Clinically, FRDA is dominated by a tabeto-cerebellar ataxic pattern, associated with pyramidal signs and various systemic manifestations. FRDA patients may present subtle signs of proprioceptive loss, such as loss of tendon reflexes and a Romberg sign, before they become frankly symptomatic. However, FRDA patients become overtly ataxic only when cerebellar symptoms appear. Most items in the scales for the assessment of neurological deficits in FRDA (e.g., Scale for the Assessment and Rating of Ataxia (SARA) or the Friedreich Ataxia Rating Scale) are performed under patients’ visual control and mainly reflect cerebellar dysfunction rather than afferent proprioceptive ataxia. Neuroimaging studies show progressive thinning of the cervical spinal cord, but to what extent this is due to shrinking of pyramidal tracts or the posterior columns is unclear (Koeppen et al., 2017, Dogan et al., 2019).
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    Evidence for genetically determined degeneration of proprioceptive tracts in Friedreich ataxia
    (Lippincott Williams and Wilkins, 2019-07-09) Marty, Brice; Naeije, Gilles; Bourguignon, Mathieu; Wens, Vincent; Jousmäki, Veikko; Lynch, David R; Gaetz, William; Goldman, Serge; Hari, Riitta; Pandolfo, Massimo; De Tiège, Xavier; Department of Art; Department of Neuroscience and Biomedical Engineering; Université libre de Bruxelles; Children's Hospital of Philadelphia
    OBJECTIVE: To assess with magnetoencephalography the developmental vs progressive character of the impairment of spinocortical proprioceptive pathways in Friedreich ataxia (FRDA). METHODS: Neuromagnetic signals were recorded from 16 right-handed patients with FRDA (9 female patients, mean age 27 years, mean Scale for the Assessment and Rating Of ataxia [SARA] score 22.25) and matched healthy controls while they performed right finger movements either actively or passively. The coupling between movement kinematics (i.e., acceleration) and neuromagnetic signals was assessed by the use of coherence at sensor and source levels. Such coupling, that is, the corticokinematic coherence (CKC), specifically indexes proprioceptive afferent inputs to the contralateral primary sensorimotor (cSM1) cortex. Nonparametric permutations and Spearman rank correlation test were used for statistics. RESULTS: In both groups of participants and movement conditions, significant coupling peaked at the cSM1 cortex. Coherence levels were 70% to 75% lower in patients with FRDA than in healthy controls in both movement conditions. In patients with FRDA, coherence levels correlated with genotype alteration (i.e., the size of GAA1 triplet expansion) and the age at symptom onset but not with disease duration or SARA score. CONCLUSION: This study provides electrophysiologic evidence demonstrating that proprioceptive impairment in FRDA is mostly genetically determined and scarcely progressive after symptom onset. It also positions CKC as a reliable, robust, specific marker of proprioceptive impairment in FRDA.