Neurologic outcomes in Friedreich ataxia

Abstract

ObjectiveTo investigate the pattern of progression of neurologic impairment in Friedreich ataxia (FRDA) and identify patients with fast disease progression as detected by clinical rating scales.MethodsClinical, demographic, and genetic data were analyzed from 54 patients with FRDA included at the Brussels site of the European Friedreich's Ataxia Consortium for Translational Studies, with an average prospective follow-up of 4 years.ResultsAfferent ataxia predated other features of FRDA, followed by cerebellar ataxia and pyramidal weakness. The Scale for the Assessment and Rating of Ataxia (SARA) best detected progression in ambulatory patients and in the first 20 years of disease duration but did not effectively capture progression in advanced disease. Dysarthria, sitting, and upper limb coordination items kept worsening after loss of ambulation. Eighty percent of patients needing support to walk lost ambulation within 2 years. Age at onset had a strong influence on progression of neurologic and functional deficits, which was maximal in patients with symptom onset before age 8 years. All these patients became unable to walk by 15 years after onset, significantly earlier than patients with later onset. Progression in the previous 1 or 2 years was not predictive of progression in the subsequent year.ConclusionsThe SARA is a sensitive outcome measure in ambulatory patients with FRDA and has an excellent correlation with functional capabilities. Ambulatory patients with onset before age 8 years showed the fastest measurable worsening. Loss of ambulation in high-risk patients is a disease milestone that should be considered as an end point in clinical trials.

Hand Dexterity and Pyramidal Dysfunction in Friedreich Ataxia, A Finger Tapping Study

“…This abnormality was more severe in those with higher SARA scores and disease duration. Progressive pyramidal tracts involvement in FRDA is supported by neuropathological, clinical, and electrophysiological findings 32,33 Weakness, spasticity, and muscle atrophy of the hands are eventually found in over two‐third of cases 34 . Accordingly, we found that FT rate slowing was more severe in patients with higher global SARA scores, reflecting more advanced disease.…”

“…Progressive pyramidal tracts involvement in FRDA is supported by neuropathological, clinical, and electrophysiological findings 32,33 Weakness, spasticity, and muscle atrophy of the hands are eventually found in over two-third of cases. 34 Accordingly, we found that FT rate slowing was more severe in patients with higher global SARA scores, reflecting more advanced disease. FRDA patients with longer disease duration also showed more severe pyramidal tract dysfunction as assessed by MEPs, with more marked increase of CMCT.…”

Central Nervous System Therapeutic Targets in Friedreich Ataxia

“…Clinically, the pattern of progression of neurological impairment in FRDA shows that the perceived onset of neurological symptoms corresponds to the appearance of cerebellar ataxia, affecting gait before stance, speech, and limb coordination. [22][23][24] Even though proprioceptive ataxia usually precedes the appearance of cerebellar symptoms, as shown by a Romberg sign in almost all patients at the time of diagnosis, 25 it is usually mild and effectively compensated by visual control. Gait and stance worsen until patients lose the ability to walk.…”

“…However, some degree of upper limb dysmetria is almost always present in recently diagnosed patients, as shown by clinical rating scales and functional tests. 22,[24][25][26] Dysarthria may be initially absent, but most patients become dysarthric within a few years after diagnosis. 22,23,27 Upper limb dysmetria, dysarthria, and eventually dysphagia continue to worsen in all patients, contributing to increasing disability in the late stages of the disease.…”

Antioxidant Therapies and Oxidative Stress in Friedreich’s Ataxia: The Right Path or Just a Diversion?

“…In addition, the influence of epigenetic and environmental factors in the progression of the pathology further impact on the capability to define the natural histories of patients. The development and consensus of new scales such as SARA [204] and mFARS [39], together with the generation of patient records containing comprehensive clinic and epidemiologic information is essential but results are still limited and dispersed. All these aspects hinder the proper classification of patients for the design and analysis of clinical tests.…”